Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Next Article in Journal
Assessing Patients beyond the Simple Optics of BMI: The Concomitant Role of Sarcopenia and BMI in Predicting Kidney Transplant Outcomes
Previous Article in Journal
TMEM9B Regulates Endosomal ClC-3 and ClC-4 Transporters
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Life
Volume 14
Issue 8
10.3390/life14081035
life-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer

by
Yu-Ting Chin
1,2,†,
Chung-Lin Tsai
3,†,
Hung-Huan Ma
4,†,
Da-Chuan Cheng
5,
Chia-Wen Tsai
1,2,6,
Yun-Chi Wang
1,2,
Hou-Yu Shih
1,2,
Shu-Yu Chang
1,2,7,
Jian Gu
6,
Wen-Shin Chang
1,2,6,* and
Da-Tian Bau
1,2,6,8,*
1
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
2
Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
3
Division of Cardiac and Vascular Surgery, Cardiovascular Center, Taichung Veterans General Hospital, Taichung 407219, Taiwan
4
Division of Nephrology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung 427003, Taiwan
5
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404333, Taiwan
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7
Department of Nephrology, Chang-Hua Hospital, Ministry of Health and Welfare, Changhua 51341, Taiwan
8
Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413305, Taiwan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this study.
Life 2024, 14(8), 1035; https://doi.org/10.3390/life14081035
Submission received: 22 July 2024 / Revised: 9 August 2024 / Accepted: 19 August 2024 / Published: 20 August 2024
(This article belongs to the Section Physiology and Pathology)
Browse Figure
Versions Notes

Abstract

:
Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28–11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05–3.45 and 2.30–17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

1. Introduction

Prostate cancer (PCa) is the second most common cancer among men worldwide and is a leading cause of cancer-related mortality. The incidence of PCa is increasing in developed countries. It is estimated that the number of PCa cases in men in the United States will reach 299,010, accounting for 29% of all cancers in 2024 [1]. Globally, there were approximately 1,466,680 new PCa cases in 2022 [2]. PCa is difficult to diagnose early. Studies have found that PCa may be related to family history, race, occupation, cadmium exposure, vasectomy, obesity, alcohol consumption, and other factors, with genetic factors possibly being the most important, though largely unrevealed [3,4,5,6,7].
The vast majority of PCas are adenocarcinomas originating from glandular cells that line the prostate gland and its tubes. Prostate carcinogenesis is a multi-stage process that begins with the development of low-grade prostatic intraepithelial neoplasia (PIN), followed by localized adenocarcinoma, and ultimately advances to metastatic disease. The pathophysiology of PCa involves complex interactions between genetic, epigenetic, hormonal, and environmental factors. Numerous genetic and epigenetic alterations have been documented in prostate tumors [8]. The most common PCa genetic alterations are translocations involving androgen-regulated promoters and the ETS family of transcription factors, such as ERG and the ETV genes [9], among which the TMPRSS2:ERG fusion occurs in approximately 50% of localized PCa tumors [10,11]. Other frequent somatic genetic alterations include MYC amplification and mutations in pathways of androgen receptor (AR), PI3K–PTEN, TGF-β/SMAD4, DNA repair, and epigenetic regulators and chromatin remodelers [8]. Because a normal prostate needs androgen and its receptor for homeostasis, targeting the AR pathway via androgen deprivation therapy (ADT) is the standard of care for PCa. Resistance to ADT results in castration-resistant PCa (CRPC) and metastatic CRPC (mCRPC), which accounts for most of the PCa death.
We have previously reported a genome-wide association study of PCa [12] together with several candidate genes [13,14,15,16,17] among Taiwanese; however, the genetic contributions to PCa susceptibility and prognosis in Taiwanese individuals are far from satisfying and need further investigation. Interleukin-10 (IL-10) is a pivotal cytokine involved in immune regulation, exerting dual roles in both promoting and inhibiting immune responses. Its impact on tumorigenesis is paradoxical, as it can both facilitate and suppress tumor development [18]. IL-10 can inhibit tumorigenesis by enhancing CD8+ T cell activity and suppressing pro-inflammatory cytokines such as IL-6 and IL-23 [19]. Conversely, IL-10 can hinder antigen presentation and suppress interferon gamma (IFN-γ), thereby potentially dampening anti-tumor immunity [19]. In the context of PCa, elevated IL-10 levels in both tissue and serum have long been recognized as prognostic indicators of PCa aggressiveness and progression [20,21,22,23,24,25]. Over-expression of IL-10 has been associated with PCa development in several studies among different populations [20,21,22,23,24,25]; however, the genotype-phenotype correlation is not well known. The IL-10 gene comprises five exons and is located on chromosome 1q31-32 [26]. Three commonly studied SNPs in the promoter region of the IL-10 gene, rs1800896, rs3021097 and rs1800872, have been reported to modulate its expression [27,28].
In this study, we examined the associations of three IL-10 promoter SNPs, rs1800896, rs3021097 and rs1800872, with the risk and aggressiveness of PCa in Taiwanese. In addition, we investigated the combinative effects of IL-10 genotype with age and smoking behavior on PCa risk and aggressiveness. Finally, we performed a comprehensive literature review of the associations of rs1800896 with PCa risk.

2. Materials and Methods

2.1. Recruitment of PCa Cases and Healthy Controls

In this study, 218 patients diagnosed with PCa were recruited from the outpatient clinics of the general surgery at China Medical University Hospital, Taichung, Taiwan. The recruitment was facilitated by the hospital’s Tissue Bank. During the same period, 436 healthy volunteers without PCa were recruited as controls. These controls were matched by age and were selected through initial random sampling from the Health Examination Cohort of the same hospital. The details of the inclusion and exclusion criteria have been published previously [12,13]. Briefly, the exclusion criteria for the control group included a history of malignancy, metastasized cancer of known or unknown origin, and any familial or genetic diseases. Additionally, control subjects lacking the specified demographic data were excluded from the study. All participants were Taiwanese citizens and the population in Taiwan is racially homogeneous. The study design and protocols have been approved and supervised by the Institutional Review Board of China Medical University Hospital (CMUH110-REC3-005). Several selected characteristics including age, smoking behaviors, family history, disease stages, and pathologic grades are summarized in Table 1.

2.2. IL-10 Genotyping Methodology

Genomic DNA was extracted from the peripheral blood of each participant as our published routine protocol [29,30]. The genotypes of IL-10 rs1800896, rs3021097, and rs1800872 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, as we have previously described [31]. The PCR primer sequences and respective restriction endonuclease for each DNA product of IL-10 rs1800896, rs3021097, and rs1800872 SNPs are summarized in Table 2. The locations of the investigated IL-10 polymorphic sites are summarized in Figure 1.

2.3. Selection of the Literature

Published articles were chosen from PubMed via EndNote, updated to 1 July 2024. The exclusion criteria were as follows: (a) articles published in non-SCI journals; (b) articles without a well-defined investigated population; (c) articles investigating small sample populations with insufficient analyzing power (fewer than 150 controls or cases, or fewer than 400 total samples); and (d) articles where the genotypic distribution does not fit the Hardy–Weinberg equilibrium (HWE).

2.4. Statistical Analysis

We used Student’s t-test to compare the mean age and the Pearson’s Chi-square test to compare the genotype frequency between the PCa case and non-PCa control groups. The association between IL-10 genotypes and PCa risk was determined using a multivariable logistic regression analysis. The tests were two-sided, and any p-value less than 0.05 was considered to be statistically significant.

3. Results

3.1. Demographics and Lifestyles for the PCa Case and Non-PCa Control Groups

The distributions of demographic characteristics, including age, smoking behaviors, and family history for the 218 PCa patients and 436 non-PCa healthy controls, are compared in Table 1. Additionally, the disease stages and pathologic grades of the PCa cases are also shown in Table 1. The mean age ± standard deviation of the cases and controls were 63.6 ± 6.9 and 63.9 ± 6.6, respectively (p = 0.58). About 81% of the cases are ever smokers, compared to 77% for the controls (p = 0.27). Among the PCa cases, 7.8% and 1.8% had a family history of any cancer in their first- and second-degree relatives, respectively; 71.1% and 28.9% were in the early and late stages, respectively; and 12.9%, 40.8%, and 46.3% of the PCa cases were of well-, moderately, and poorly differentiated grades, respectively (Table 1).

3.2. Contributions of IL-10 Genotypes to PCa Risk

Table 3 reveals the distributions of IL-10 genotypes among the PCa patients and non-PCa control subjects. All the three IL-10 genotypes fit well with the Hardy–Weinberg equilibrium in the controls (p = 0.3428, 0.2680, and 0.6034, respectively). The distributions of the three genotypes were not significantly different between the cases and controls (Ptrend = 0.1755, 0.8296, and 0.6547, respectively) (Table 3). There were suggestive associations between the rs1800896 genotypes and PCa risk: the homozygous variant GG and heterozygous variant AG genotype were associated with elevated risks of PCa (adjusted OR = 1.18 and 1.98, 95% CI = 0.79–1.68 and 0.85–3.75, p-value = 0.3933 and 0.1451, respectively) (Table 3).

3.3. Contributions of IL-10 Alleles to PCa Risk

The allelic frequencies of the three IL-10 SNPs among the PCa patients and non-PCa healthy controls were also examined (Table 4). In line with the findings in Table 3, the rs3021097 and rs1800872 allelic frequencies was not significantly different between the PCa case and non-PCa control groups (p = 0.6106 and 0.3885, respectively) (Table 4). However, there was a suggestive association between the variant G allele of rs1800896 and an increased risk of PCa (OR = 1.33, 95% CI = 0.97–1.83, p = 0.0906).

3.4. Association of IL-10 rs1800896 Genotypes with PCa Risk Stratified by Clinicopathologic Characteristics

We further analyzed the association of rs1800896 genotypes with PCa risk stratified by clinicopathologic characteristics including age, smoking behavior, and disease stage (Table 5). Interestingly, a significant association was observed in smokers, but not in non-smokers. The ORs (95% CI) for the heterozygous variant genotype (AG) and homozygous variant genotype (GG) were 1.46 (0.96–2.24) and 3.90 (1.28–11.89), p = 0.0983 and 0.0231, respectively. In addition, the AG and GGs were associated with a significantly increased risk of PCa in late-stage patients (adjusted OR = 1.92, 95% CI = 1.09–3.68, p = 0.0452; and adjusted OR = 5.81, 95% CI = 2.54–14.77, p = 0.0003, respectively), but not in early-stage patients.

4. Discussion

In recent years, new advances in molecular and genetic studies have demonstrated a causal relationship between chronic infection, chronic inflammation, and PCa [32,33]. Chronic inflammation has been hypothesized to be a cause of PCa, contributing to carcinogenesis during both disease initiation and subsequent progression [34,35]. Over-expression of IL-10 has been associated with elevated PCa risk [20,21,22,23,24,25]. Elevated IL-10 levels have been detected in the serum of PCa patients, correlating with poor prognosis and higher Gleason scores [22,23,24]. In addition, the expression of IL-10 is significantly higher in PCa tumor tissues than in normal prostates and benign prostate lesions and correlates with a high grade and stage of prostate carcinoma [21,36]. IL-10 may be produced by either tumor cells themselves or by immune cells [21,37,38,39,40,41]. IL-10 is predominantly expressed in monocytes and Th2 lymphocytes [42,43]. IL-10 promotes tumor growth in PCa by suppressing the antitumor immune response through its effects on immune cells [44] and by directly acting on the PCa cells [45]. Its suppression of the antitumor immune response includes the suppression of myeloid and T effector cell function [46,47]. IL-10 can upregulate the expression of PDL1 on myeloid cells [48], whereas PDL1 binds to its receptor PD1 on T cells, inhibiting T cell function and hence its antitumor immune response [49]. IL-10 can also directly act on prostate cancer cells. For example, it can induce neuroendocrine differentiation, inhibit AR activity, and upregulate PDL1 in PCa cells, thereby promoting PCa progression [50].
In this study, the association of three commonly studied IL-10 promoter SNPs and PCa risk was examined among a Taiwanese population containing 218 PCa cases and 436 non-PCa healthy controls. None of the SNPs were significantly associated with the risks of PCa, although a suggestive association between rs1800896 and the risk of PCa was observed (Table 3 and Table 4). In the literature, the rs1800896 AA genotype has been associated with a higher risk of developing PCa in Croatian [51] and Indian populations [52]. However, these two articles had limitations: one had a small sample size (control:case = 120:120), and the distribution of genotypes in the controls in the other did not fit HWE. On the contrary, it has been reported that the rs1800896 AA genotype was associated with decreased risks of PCa in USA [53], UK [54], and Indian populations [55]. Several other studies of populations of European ancestry [56,57,58,59,60,61,62] and a study of Chinese populations [63] did not find significant associations (Table 6). These heterogeneous results may be due to small sample sizes, diverse populations, differing genetic architecture, and a range of environmental exposures.
Regarding the biochemical mechanisms underlying our observed association, the literature has consistently demonstrated that individuals with the IL-10 rs1800896 (A-1082G) variant AG and GGs have elevated serum levels of IL-10 compared to those with the wild-type AA genotype [64,65,66,67]. Moreover, the rs1800896 SNP is located within the transcriptional factor binding sites and the variant G-allele has higher transcriptional activity than the A-allele in various cell lines [68,69,70,71]. These data strongly support our observations that the variant genotypes AG and GG of this SNP correlate with late stages of PCa and significantly increase the risk of PCa in smokers, because IL-10 is a pro-tumorigenic cytokine in PCa and the variant genotypes increase IL-10 level, thus promoting PCa development and progression.
To investigate how these SNPs modulate IL-10 expression, Reuss et al. [68] performed a thorough study characterizing the three IL-10 promoter SNPs on transcriptional activity and their bindings to transcriptional factors using luciferase reporter gene and electrophoretic mobility shift assays (EMSA). They found that the rs1800896 (A-1082G) lies within an ETS-consensus binding site and that the A-allele specifically binds to an ETS-family transcriptional factor SPI1/PU.1, whereas the G-allele does not. They reasoned that the differential SPI1 binding accounts for the different transcriptional activity and that SPI1 binding to the A-allele negatively regulates IL-10 expression. The negative transcriptional regulation by SPI1 binding has also been reported for other genes [72,73]. In addition, several studies have shown that another transcription factor, Sp1, only bound to the G allele in response to inflammatory stimulation, resulting in a much larger increase in IL-10 mRNA and protein levels in B-cell lines with the GG than the AA genotype [69,70,71]. It appears that both positive and negative transcriptional regulation contribute to the higher transcriptional activity of the G-alleles of rs1800896.
The associations of the other two SNPs, rs3021097 (T-819C) and rs1800872 (A-592C), with IL-10 expression were inconsistent in the literature [74,75]. They are not located within transcription factor binding sites and do not bind to transcriptional factors in EMSA experiments [68]. It is thus not surprising that we did not observe any significant associations of these two SNPs with PCa risk.
There have been lots of epidemiological studies investigating the associations between IL-10 promoter SNPs, which may alter the function of this cytokine itself and its related cellular behavior and lead to the development of human disorders. The rs1800896 has been reported to be associated with oral cancer [76,77], nasopharyngeal carcinoma [78], papillary thyroid cancer [79,80], gastric cancer [81,82,83], lung cancer [84], breast cancer [85], renal cell carcinoma [86,87], cervical cancer [88,89], lymphoma [90,91], and leukemia [92,93]. The rs3021097 was reported to be associated with gastric cancer [84,94,95], renal cell carcinoma [96], lung cancer [97], cervical cancer [98], bladder cancer [99], and leukemia [28,100]. The rs1800872 was associated with oral cancer [101], esophageal cancer [102], gastric cancer [103], lung cancer [84], breast cancer [104], cervical cancer [105,106], lymphoma [107], and leukemia [100]. Future larger studies would be necessary to clarify the roles of these SNPs in cancer predisposition due to their modest effect size. In addition, collecting comprehensive clinical and pathological data for all cases, along with full follow-up and periodic assessment of therapeutic responses, is crucial for precise genomics. Recruiting appropriately matched control subjects in terms of age, gender, and lifestyle behaviors is extremely important. Furthermore, a proper combination of multiple SNPs in a single candidate gene, such as IL-10 rs1800896, rs3021097, and rs1800872 in this study, can provide informative coverage of the entire gene.
IL-10 is a major suppressor of immune response and plays important roles in a variety of human diseases, thus becoming an attractive therapeutic target [108,109]. In an IL-10 transgenic mouse model, high expression of IL-10 failed to control an immunogenic lung tumor; however, administering an anti-IL-10 antibody significantly inhibited tumor growth [110]. Likewise, IL-10 knock-out mice are resistant to UV-induced skin carcinogenesis, correlating with a potent Th1 response in these mice [111]. Ruffell et al. [112] showed that blocking IL-10 signaling using an IL-10 receptor (IL-10R) monoclonal antibody enhanced paclitaxel and carboplatin efficacy in a breast cancer model. Blocking IL-10 could also suppress the metastatic behaviors of colorectal cancer cells [113] and promote gastrointestinal cancer cell death [114]. These data support the concept that IL-10 suppresses the anti-tumoral immune response, and blocking IL-10 can strengthen the anti-tumoral immune response and inhibit tumor growth. However, it should be cautioned that IL-10 plays a dual role in human carcinogenesis depending on specific cell types and contexts. It can inhibit certain cancers, and a PEG-conjugated human IL-10 has been on clinical trial for pancreatic cancer [109,115]. Future studies should test the clinical potential of targeting IL-10 and its downstream molecules in the context of PCa and investigate the pleiotropic effects of IL-10 in different cancers.
The well-established risk factors for PCa include age, ethnicity, family history, genetic predisposition, diet, and environmental factors [116,117,118,119,120,121]. We performed stratified analyses on age and did not find significant differences in the associations of these SNPs with PCa risks in young and old aged groups. Smoking is inversely associated with overall PCa incidence, but may lead to more aggressive PCa tumors and worse prognosis of PCa patients [122,123,124]. Our stratified analyses demonstrated that the variant genotypes at rs1800896 increases the likelihood of PCa among smokers (Table 6), and are associated with increased risks of late-stage PCa (Table 5). In clinical practice, determining IL-10 genotypes alongside smoking history may aid in developing precise personalized screening and prevention strategies against aggressive PCa. The molecular mechanisms underlying the associations of the IL-10 rs1800896 variant genotypes with PCa risk in smokers and with aggressive PCa remains unclear and warrants future investigation.

5. Conclusions

In conclusion, this is the first report of three IL-10 promoter SNPs in relation to PCa susceptibility in Taiwanese. We found significant associations of the IL-10 rs1800896 variant genotypes with PCa risk in smokers and with aggressive PCa. Further studies are necessary to validate the IL-10 genetic variants as PCa predisposition markers in diverse populations and investigate the molecular mechanisms underlying the observed associations.

Author Contributions

Conceptualization, Y.-T.C., C.-L.T., W.-S.C. and D.-T.B.; methodology, Y.-T.C., H.-H.M. and D.-C.C.; validation, C.-W.T., Y.-C.W. and H.-Y.S.; formal analysis, W.-S.C. and S.-Y.C.; investigation, W.-S.C. and Y.-T.C.; resources, C.-L.T., H.-H.M., D.-C.C. and S.-Y.C.; data curation, C.-W.T., D.-T.B. and W.-S.C.; writing—original draft, Y.-T.C., W.-S.C., D.-T.B. and J.G.; writing—review and editing, J.G., D.-T.B. and W.-S.C.; supervision, D.-T.B.; project administration, D.-T.B. and W.-S.C. All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by Taichung Veterans General Hospital (TCVGH-1134801B) and Taichung Tzu Chi Hospital (TTCRD113-17). The funders had no role in study design, patient collection, experiment conduction, statistical analysis, data annotation, or decision to publish or preparation of the manuscript.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of China Medical University Hospital (CMUH110-REC3-005).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The genotyping results and clinical data supporting the findings of this study are available from the corresponding author upon reasonable requests via email at [email protected].

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Siegel, R.L.; Giaquinto, A.N.; Jemal, A. Cancer statistics, 2024. CA Cancer J. Clin. 2024, 74, 12–49. [Google Scholar] [CrossRef] [PubMed]
  2. Bray, F.; Laversanne, M.; Sung, H.; Ferlay, J.; Siegel, R.L.; Soerjomataram, I.; Jemal, A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024, 74, 229–263. [Google Scholar] [CrossRef] [PubMed]
  3. Fullwood, D.; Gunderson, J.; Snipe, B.; Villasenor, I.; Asto-Flores, E.; Pressey, S.; Hale, R.; Odedina, F.T. Prostate Cancer Screening and Strategies, Florida Behavioral Risk Factor Surveillance System, 2012–2020. Prev. Chronic Dis. 2023, 20, E108. [Google Scholar] [CrossRef]
  4. Zhao, J.; Stockwell, T.; Roemer, A.; Chikritzhs, T. Is alcohol consumption a risk factor for prostate cancer? A systematic review and meta-analysis. BMC Cancer 2016, 16, 845. [Google Scholar] [CrossRef]
  5. Dombi, G.W.; Rosbolt, J.P.; Severson, R.K. Neural network analysis of employment history as a risk factor for prostate cancer. Comput. Biol. Med. 2010, 40, 751–757. [Google Scholar] [CrossRef] [PubMed]
  6. Krstev, S.; Knutsson, A. Occupational Risk Factors for Prostate Cancer: A Meta-analysis. J. Cancer Prev. 2019, 24, 91–111. [Google Scholar] [CrossRef] [PubMed]
  7. Guess, H.A. Is vasectomy a risk factor for prostate cancer? Eur. J. Cancer 1993, 29, 1055–1060. [Google Scholar] [CrossRef] [PubMed]
  8. Wang, G.; Zhao, D.; Spring, D.J.; DePinho, R.A. Genetics and biology of prostate cancer. Genes Dev. 2018, 32, 1105–1140. [Google Scholar] [CrossRef] [PubMed]
  9. Sizemore, G.M.; Pitarresi, J.R.; Balakrishnan, S.; Ostrowski, M.C. The ETS family of oncogenic transcription factors in solid tumours. Nat. Rev. Cancer 2017, 17, 337–351. [Google Scholar] [CrossRef] [PubMed]
  10. Tomlins, S.A.; Rhodes, D.R.; Perner, S.; Dhanasekaran, S.M.; Mehra, R.; Sun, X.W.; Varambally, S.; Cao, X.; Tchinda, J.; Kuefer, R.; et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005, 310, 644–648. [Google Scholar] [CrossRef] [PubMed]
  11. Tomlins, S.A.; Bjartell, A.; Chinnaiyan, A.M.; Jenster, G.; Nam, R.K.; Rubin, M.A.; Schalken, J.A. ETS gene fusions in prostate cancer: From discovery to daily clinical practice. Eur. Urol. 2009, 56, 275–286. [Google Scholar] [CrossRef]
  12. Bau, D.T.; Tsai, C.W.; Chang, W.S.; Yang, J.S.; Liu, T.Y.; Lu, H.F.; Wang, Y.W.; Tsai, F.J. Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study. Mol. Carcinog. 2024, 63, 617–628. [Google Scholar] [CrossRef] [PubMed]
  13. Liao, C.H.; Chang, W.S.; Hsu, W.L.; Hu, P.S.; Wu, H.C.; Hsu, S.W.; Wang, B.R.; Yueh, T.C.; Chen, C.H.; Hsia, T.C.; et al. Association of Matrix Metalloproteinase-7 Genotypes With Prostate Cancer Risk. Anticancer Res. 2023, 43, 381–387. [Google Scholar] [CrossRef] [PubMed]
  14. Li, P.H.; Liao, C.H.; Huang, W.C.; Chang, W.S.; Wu, H.C.; Hsu, S.W.; Chen, K.Y.; Wang, Z.H.; Hsia, T.C.; Bau, D.T.; et al. Association of Matrix Metalloproteinase-2 Genotypes With Prostate Cancer Risk. Anticancer Res. 2023, 43, 343–349. [Google Scholar] [CrossRef] [PubMed]
  15. Liao, C.H.; Wu, H.C.; Hu, P.S.; Hsu, S.W.; Shen, T.C.; Hsia, T.C.; Chang, W.S.; Tsai, C.W.; Bau, D.T. The Association of Matrix Metalloproteinase-1 Promoter Polymorphisms with Prostate Cancer in Taiwanese Patients. Anticancer Res. 2018, 38, 3907–3911. [Google Scholar] [CrossRef] [PubMed]
  16. Wu, H.C.; Chang, C.H.; Tsou, Y.A.; Tsai, C.W.; Lin, C.C.; Bau, D.T. Significant association of caveolin-1 (CAV1) genotypes with prostate cancer susceptibility in Taiwan. Anticancer Res. 2011, 31, 745–749. [Google Scholar] [PubMed]
  17. Chang, C.H.; Chiu, C.F.; Wu, H.C.; Tseng, H.C.; Wang, C.H.; Lin, C.C.; Tsai, C.W.; Liang, S.Y.; Wang, C.L.; Bau, D.T. Significant association of XRCC4 single nucleotide polymorphisms with prostate cancer susceptibility in Taiwanese males. Mol. Med. Rep. 2008, 1, 525–530. [Google Scholar] [CrossRef] [PubMed]
  18. Mannino, M.H.; Zhu, Z.; Xiao, H.; Bai, Q.; Wakefield, M.R.; Fang, Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett. 2015, 367, 103–107. [Google Scholar] [CrossRef] [PubMed]
  19. Ouyang, W.; O’Garra, A. IL-10 Family Cytokines IL-10 and IL-22: From Basic Science to Clinical Translation. Immunity 2019, 50, 871–891. [Google Scholar] [CrossRef] [PubMed]
  20. Filella, X.; Alcover, J.; Zarco, M.A.; Beardo, P.; Molina, R.; Ballesta, A.M. Analysis of type T1 and T2 cytokines in patients with prostate cancer. Prostate 2000, 44, 271–274. [Google Scholar] [CrossRef] [PubMed]
  21. Cardillo, M.R.; Ippoliti, F. IL-6, IL-10 and HSP-90 expression in tissue microarrays from human prostate cancer assessed by computer-assisted image analysis. Anticancer Res. 2006, 26, 3409–3416. [Google Scholar] [PubMed]
  22. Dwivedi, S.; Goel, A.; Natu, S.M.; Mandhani, A.; Khattri, S.; Pant, K.K. Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: A prospective study. Asian Pac. J. Cancer Prev. 2011, 12, 1843–1848. [Google Scholar]
  23. Ugge, H.; Downer, M.K.; Carlsson, J.; Bowden, M.; Davidsson, S.; Mucci, L.A.; Fall, K.; Andersson, S.O.; Andren, O. Circulating inflammation markers and prostate cancer. Prostate 2019, 79, 1338–1346. [Google Scholar] [CrossRef]
  24. Chen, H.; Zhou, J.; Luo, J.; Wu, Y.; Qian, Y.; Shi, Y.; Qu, F.; Shi, B.; Ding, J.; Cui, X.; et al. Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China. Front. Immunol. 2022, 13, 901176. [Google Scholar] [CrossRef]
  25. Al-Nasralla, A.S.H.; Hussian, S.S.; Tektook, N.K. Immunological analysis of Interleukin-10 (IL-10), tumor necrosis factor-a (TNF-a), and Prostate-specific antigen (PSA) in benign and malignant prostate cancer. Hum. Antibodies 2023, 8, 46. [Google Scholar] [CrossRef] [PubMed]
  26. Eskdale, J.; Kube, D.; Tesch, H.; Gallagher, G. Mapping of the human IL10 gene and further characterization of the 5′ flanking sequence. Immunogenetics 1997, 46, 120–128. [Google Scholar] [CrossRef] [PubMed]
  27. Lowe, P.R.; Galley, H.F.; Abdel-Fattah, A.; Webster, N.R. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit. Care Med. 2003, 31, 34–38. [Google Scholar] [CrossRef] [PubMed]
  28. Yao, C.J.; Du, W.; Chen, H.B.; Xiao, S.; Wang, C.H.; Fan, Z.L. Associations of IL-10 gene polymorphisms with acute myeloid leukemia in Hunan, China. Asian Pac. J. Cancer Prev. 2013, 14, 2439–2442. [Google Scholar] [CrossRef]
  29. Wang, Y.C.; He, J.L.; Tsai, C.L.; Tzeng, H.E.; Chang, W.S.; Pan, S.H.; Chen, L.H.; Su, C.H.; Lin, J.C.; Hung, C.C.; et al. The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan. Life 2023, 14, 9. [Google Scholar] [CrossRef]
  30. Chen, C.H.; Shih, L.C.; Hsu, S.W.; Tien, H.C.; Liu, Y.F.; Wang, Y.C.; Tsai, C.W.; Bau, D.T.; Chang, W.S. Association of Matrix Metalloproteinase-9 Genotypes With Nasopharyngeal Carcinoma Risk. In Vivo 2024, 38, 1731–1739. [Google Scholar] [CrossRef]
  31. Chen, K.Y.; Chien, W.C.; Liao, J.M.; Tsai, C.W.; Chang, W.S.; Su, C.H.; Hsu, S.W.; Wang, H.C.; Bau, D.T. Contribution of Interleukin-10 Genotype to Triple Negative Breast Cancer Risk. Anticancer Res. 2021, 41, 2451–2457. [Google Scholar] [CrossRef] [PubMed]
  32. Gurel, B.; Lucia, M.S.; Thompson, I.M., Jr.; Goodman, P.J.; Tangen, C.M.; Kristal, A.R.; Parnes, H.L.; Hoque, A.; Lippman, S.M.; Sutcliffe, S.; et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol. Biomark. Prev. 2014, 23, 847–856. [Google Scholar] [CrossRef]
  33. Mason, T.E.; Ricks-Santi, L.; Chen, W.; Apprey, V.; Joykutty, J.; Ahaghotu, C.; Kittles, R.; Bonney, G.; Dunston, G.M. Association of CD14 variant with prostate cancer in African American men. Prostate 2010, 70, 262–269. [Google Scholar] [CrossRef] [PubMed]
  34. De Marzo, A.M.; Nakai, Y.; Nelson, W.G. Inflammation, atrophy, and prostate carcinogenesis. Urol. Oncol. 2007, 25, 398–400. [Google Scholar] [CrossRef] [PubMed]
  35. De Marzo, A.M.; Platz, E.A.; Sutcliffe, S.; Xu, J.; Gronberg, H.; Drake, C.G.; Nakai, Y.; Isaacs, W.B.; Nelson, W.G. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer 2007, 7, 256–269. [Google Scholar] [CrossRef] [PubMed]
  36. Bakir, W.A.; Gaidan, H.A.; Al-Kaabi, M.M. Immunohistochemical expression of interlukin10 (IL10) and heat shock protein-90 (HSP-90) in prostatic carcinoma. Indian J. Pathol. Microbiol. 2020, 63, 230–234. [Google Scholar] [CrossRef] [PubMed]
  37. Gastl, G.A.; Abrams, J.S.; Nanus, D.M.; Oosterkamp, R.; Silver, J.; Liu, F.; Chen, M.; Albino, A.P.; Bander, N.H. Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression. Int. J. Cancer 1993, 55, 96–101. [Google Scholar] [CrossRef] [PubMed]
  38. Verma, S.; Kushwaha, P.P.; Shankar, E.; Ponsky, L.E.; Gupta, S. Increased cytokine gene expression and cognition risk associated with androgen deprivation therapy. Prostate 2022, 82, 1389–1399. [Google Scholar] [CrossRef] [PubMed]
  39. Hao, N.B.; Lu, M.H.; Fan, Y.H.; Cao, Y.L.; Zhang, Z.R.; Yang, S.M. Macrophages in tumor microenvironments and the progression of tumors. Clin. Dev. Immunol. 2012, 2012, 948098. [Google Scholar] [CrossRef] [PubMed]
  40. Moore, K.W.; de Waal Malefyt, R.; Coffman, R.L.; O’Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 2001, 19, 683–765. [Google Scholar] [CrossRef] [PubMed]
  41. Saraiva, M.; O’Garra, A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 2010, 10, 170–181. [Google Scholar] [CrossRef] [PubMed]
  42. Chu, C.M.; Chung, C.J.; Huang, C.Y.; Yu, C.C.; Wang, C.H.; Li, L.F.; Wu, H.P. Serial Increases in Human Leukocyte Antigen-DR Expression and Decreases in Interleukin-10 Expression in Alveolar Monocytes of Survivors of Pneumonia-Related Acute Respiratory Distress Syndrome. Biology 2022, 11, 1793. [Google Scholar] [CrossRef] [PubMed]
  43. Xu, F.; Yu, S.; Qin, M.; Mao, Y.; Jin, L.; Che, N.; Liu, S.; Ge, R. Hydrogen-Rich Saline Ameliorates Allergic Rhinitis by Reversing the Imbalance of Th1/Th2 and Up-Regulation of CD4+CD25+Foxp3+Regulatory T Cells, Interleukin-10, and Membrane-Bound Transforming Growth Factor-beta in Guinea Pigs. Inflammation 2018, 41, 81–92. [Google Scholar] [CrossRef]
  44. Dennis, K.L.; Blatner, N.R.; Gounari, F.; Khazaie, K. Current status of interleukin-10 and regulatory T-cells in cancer. Curr. Opin. Oncol. 2013, 25, 637–645. [Google Scholar] [CrossRef]
  45. Stearns, M.E.; Hu, Y.; Wang, M. IL-10 signaling via IL-10E1 is dependent on tyrosine phosphorylation in the IL-10R alpha chain in human primary prostate cancer cell lines. Oncogene 2003, 22, 3781–3791. [Google Scholar] [CrossRef] [PubMed]
  46. Chen, Y.; Song, Y.; Du, W.; Gong, L.; Chang, H.; Zou, Z. Tumor-associated macrophages: An accomplice in solid tumor progression. J. Biomed. Sci. 2019, 26, 78. [Google Scholar] [CrossRef]
  47. Bolpetti, A.; Silva, J.S.; Villa, L.L.; Lepique, A.P. Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth. BMC Immunol. 2010, 11, 27. [Google Scholar] [CrossRef]
  48. Taube, J.M.; Young, G.D.; McMiller, T.L.; Chen, S.; Salas, J.T.; Pritchard, T.S.; Xu, H.; Meeker, A.K.; Fan, J.; Cheadle, C.; et al. Differential Expression of Immune-Regulatory Genes Associated with PD-L1 Display in Melanoma: Implications for PD-1 Pathway Blockade. Clin. Cancer. Res. 2015, 21, 3969–3976. [Google Scholar] [CrossRef]
  49. Butte, M.J.; Keir, M.E.; Phamduy, T.B.; Sharpe, A.H.; Freeman, G.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007, 27, 111–122. [Google Scholar] [CrossRef]
  50. Samiea, A.; Yoon, J.S.J.; Ong, C.J.; Zoubeidi, A.; Chamberlain, T.C.; Mui, A.L. Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells. Prostate Cancer 2020, 2020, 5305306. [Google Scholar] [CrossRef]
  51. Horvat, V.; Mandic, S.; Marczi, S.; Mrcela, M.; Galic, J. Association of IL-1beta and IL-10 Polymorphisms with Prostate Cancer Risk and Grade of Disease in Eastern Croatian Population. Coll. Antropol. 2015, 39, 393–400. [Google Scholar]
  52. Kesarwani, P.; Ahirwar, D.K.; Mandhani, A.; Singh, A.N.; Dalela, D.; Srivastava, A.N.; Mittal, R.D. IL-10-1082 G>A: A risk for prostate cancer but may be protective against progression of prostate cancer in North Indian cohort. World J. Urol. 2009, 27, 389–396. [Google Scholar] [CrossRef]
  53. Wang, M.H.; Helzlsouer, K.J.; Smith, M.W.; Hoffman-Bolton, J.A.; Clipp, S.L.; Grinberg, V.; De Marzo, A.M.; Isaacs, W.B.; Drake, C.G.; Shugart, Y.Y.; et al. Association of IL10 and other immune response-and obesity-related genes with prostate cancer in CLUE II. Prostate 2009, 69, 874–885. [Google Scholar] [CrossRef]
  54. McCarron, S.L.; Edwards, S.; Evans, P.R.; Gibbs, R.; Dearnaley, D.P.; Dowe, A.; Southgate, C.; Easton, D.F.; Eeles, R.A.; Howell, W.M. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res. 2002, 62, 3369–3372. [Google Scholar]
  55. Bandil, K.; Singhal, P.; Dogra, A.; Rawal, S.K.; Doval, D.C.; Varshney, A.K.; Bharadwaj, M. Association of SNPs/haplotypes in promoter of TNF A and IL-10 gene together with life style factors in prostate cancer progression in Indian population. Inflamm. Res. 2017, 66, 1085–1097. [Google Scholar] [CrossRef]
  56. Winchester, D.A.; Till, C.; Goodman, P.J.; Tangen, C.M.; Santella, R.M.; Johnson-Pais, T.L.; Leach, R.J.; Xu, J.; Zheng, S.L.; Thompson, I.M.; et al. Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride arm in the Prostate Cancer Prevention Trial. Prostate 2017, 77, 908–919. [Google Scholar] [CrossRef] [PubMed]
  57. Dluzniewski, P.J.; Wang, M.H.; Zheng, S.L.; De Marzo, A.M.; Drake, C.G.; Fedor, H.L.; Partin, A.W.; Han, M.; Fallin, M.D.; Xu, J.; et al. Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence. Cancer Epidemiol. Biomark. Prev. 2012, 21, 1774–1782. [Google Scholar] [CrossRef] [PubMed]
  58. VanCleave, T.T.; Moore, J.H.; Benford, M.L.; Brock, G.N.; Kalbfleisch, T.; Baumgartner, R.N.; Lillard, J.W., Jr.; Kittles, R.A.; Kidd, L.C. Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk. Prostate 2010, 70, 341–352. [Google Scholar] [CrossRef] [PubMed]
  59. Zabaleta, J.; Lin, H.Y.; Sierra, R.A.; Hall, M.C.; Clark, P.E.; Sartor, O.A.; Hu, J.J.; Ochoa, A.C. Interactions of cytokine gene polymorphisms in prostate cancer risk. Carcinogenesis 2008, 29, 573–578. [Google Scholar] [CrossRef]
  60. Faupel-Badger, J.M.; Kidd, L.C.; Albanes, D.; Virtamo, J.; Woodson, K.; Tangrea, J.A. Association of IL-10 polymorphisms with prostate cancer risk and grade of disease. Cancer Causes Control 2008, 19, 119–124. [Google Scholar] [CrossRef]
  61. Michaud, D.S.; Daugherty, S.E.; Berndt, S.I.; Platz, E.A.; Yeager, M.; Crawford, E.D.; Hsing, A.; Huang, W.Y.; Hayes, R.B. Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer. Cancer Res. 2006, 66, 4525–4530. [Google Scholar] [CrossRef] [PubMed]
  62. Xu, J.; Lowey, J.; Wiklund, F.; Sun, J.; Lindmark, F.; Hsu, F.C.; Dimitrov, L.; Chang, B.; Turner, A.R.; Liu, W.; et al. The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk. Cancer Epidemiol. Biomark. Prev. 2005, 14, 2563–2568. [Google Scholar] [CrossRef] [PubMed]
  63. Liu, J.; Song, B.; Bai, X.; Liu, W.; Li, Z.; Wang, J.; Zheng, Y.; Wang, Z. Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese. BMC Cancer 2010, 10, 456. [Google Scholar] [CrossRef] [PubMed]
  64. Lv, C.; Wang, Y.; Wang, J.; Zhang, H.; Xu, H.; Zhang, D. Association of Interleukin-10 gene polymorphisms with ankylosing spondylitis. Clin. Investig. Med. 2011, 34, E370–E376. [Google Scholar] [CrossRef] [PubMed]
  65. Miteva, L.D.; Stanilov, N.S.; Deliysky, T.S.; Stanilova, S.A. Significance of -1082A/G polymorphism of IL10 gene for progression of colorectal cancer and IL-10 expression. Tumor Biol. 2014, 35, 12655–12664. [Google Scholar] [CrossRef] [PubMed]
  66. Fathy, M.M.; Elsaadany, H.F.; Ali, Y.F.; Farghaly, M.A.; Hamed, M.E.; Ibrahim, H.E.; Noah, M.A.; Allah, M.A.; Elashkar, S.S.; Abdelsalam, N.I.; et al. Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: A case-control study. Ital. J. Pediatr. 2017, 43, 9. [Google Scholar] [CrossRef] [PubMed]
  67. Azab, S.F.; Abdalhady, M.A.; Elsaadany, H.F.; Elkomi, M.A.; Elhindawy, E.M.; Sarhan, D.T.; Salam, M.M.; Allah, M.A.; Emam, A.A.; Noah, M.A.; et al. Interleukin-10-1082 G/A gene polymorphisms in Egyptian children with CAP: A case-control study. Medicine 2016, 95, e4013. [Google Scholar] [CrossRef] [PubMed]
  68. Reuss, E.; Fimmers, R.; Kruger, A.; Becker, C.; Rittner, C.; Hohler, T. Differential regulation of interleukin-10 production by genetic and environmental factors--a twin study. Genes Immun. 2002, 3, 407–413. [Google Scholar] [CrossRef] [PubMed]
  69. Larsson, L.; Johansson, P.; Jansson, A.; Donati, M.; Rymo, L.; Berglundh, T. The Sp1 transcription factor binds to the G-allele of the-1087 IL-10 gene polymorphism and enhances transcriptional activation. Genes Immun. 2009, 10, 280–284. [Google Scholar] [CrossRef] [PubMed]
  70. Larsson, L.; Rymo, L.; Berglundh, T. Sp1 binds to the G allele of the-1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production. Genes Immun. 2010, 11, 181–187. [Google Scholar] [CrossRef] [PubMed]
  71. Larsson, L.; Thorbert-Mros, S.; Rymo, L.; Berglundh, T. Interleukin-10 genotypes of the -1087 single nucleotide polymorphism influence sp1 expression in periodontitis lesions. J. Periodontol. 2011, 82, 1376–1382. [Google Scholar] [CrossRef] [PubMed]
  72. Borras, F.E.; Lloberas, J.; Maki, R.A.; Celada, A. Repression of I-A beta gene expression by the transcription factor PU.1. J. Biol. Chem. 1995, 270, 24385–24391. [Google Scholar] [CrossRef]
  73. Harendza, S.; Lovett, D.H.; Stahl, R.A. The hematopoietic transcription factor PU.1 represses gelatinase A transcription in glomerular mesangial cells. J. Biol. Chem. 2000, 275, 19552–19559. [Google Scholar] [CrossRef] [PubMed]
  74. Dwivedi, S.; Goel, A.; Khattri, S.; Mandhani, A.; Sharma, P.; Misra, S.; Pant, K.K. Genetic variability at promoters of IL-18 (pro-) and IL-10 (anti-) inflammatory gene affects susceptibility and their circulating serum levels: An explorative study of prostate cancer patients in North Indian populations. Cytokine 2015, 74, 117–122. [Google Scholar] [CrossRef]
  75. Men, T.; Yu, C.; Wang, D.; Liu, F.; Li, J.; Qi, X.; Yang, C.; Jiang, W.; Wei, X.; Li, X.; et al. The impact of interleukin-10 (IL-10) gene 4 polymorphisms on peripheral blood IL-10 variation and prostate cancer risk based on published studies. Oncotarget 2017, 8, 45994–46005. [Google Scholar] [CrossRef]
  76. Tsai, C.W.; Chang, W.S.; Lin, K.C.; Shih, L.C.; Tsai, M.H.; Hsiao, C.L.; Yang, M.D.; Lin, C.C.; Bau, D.T. Significant association of Interleukin-10 genotypes and oral cancer susceptibility in Taiwan. Anticancer Res. 2014, 34, 3731–3737. [Google Scholar] [PubMed]
  77. You, Y.; Du, X.; Fan, M.; Wu, B.; Xie, C. Association between IL-10 polymorphisms (-1082A/G, -592A/C and -819T/C) and oral cancer risk. Int. J. Clin. Exp. Med. 2015, 8, 13187–13194. [Google Scholar]
  78. Tsai, C.W.; Tsai, M.H.; Shih, L.C.; Chang, W.S.; Lin, C.C.; Bau, D.T. Association of interleukin-10 (IL10) promoter genotypes with nasopharyngeal carcinoma risk in Taiwan. Anticancer Res. 2013, 33, 3391–3396. [Google Scholar]
  79. Cil, E.; Kumral, A.; Kanmaz-Ozer, M.; Vural, P.; Dogru-Abbasoglu, S.; Altuntas, Y.; Uysal, M. Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer. Mol. Biol. Rep. 2014, 41, 3091–3097. [Google Scholar] [CrossRef]
  80. Erdogan, M.; Karadeniz, M.; Ozbek, M.; Ozgen, A.G.; Berdeli, A. Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population. J. Endocrinol. Investig. 2008, 31, 750–754. [Google Scholar] [CrossRef]
  81. Sun, F.; Sun, Y.; Zhang, D.; Zhang, J.; Song, B.; Zheng, H. Association of interleukin-10 gene polymorphism with cachexia in Chinese patients with gastric cancer. Ann. Clin. Lab. Sci. 2010, 40, 149–155. [Google Scholar] [PubMed]
  82. Kuo, W.H.; Huang, C.Y.; Fu, C.K.; Hsieh, Y.H.; Liao, C.H.; Hsu, C.M.; Huang, Y.K.; Tsai, C.W.; Chang, W.S.; Bau, D.T. Effects of interleukin-10 polymorphisms and smoking on the risk of gastric cancer in Taiwan. In Vivo 2014, 28, 967–971. [Google Scholar]
  83. Cardenas, D.M.; Sanchez, A.C.; Rosas, D.A.; Rivero, E.; Paparoni, M.D.; Cruz, M.A.; Suarez, Y.P.; Galvis, N.F. Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Ralpha genes and profile of circulating cytokines in patients with gastric Cancer. BMC Gastroenterol. 2018, 18, 184. [Google Scholar] [CrossRef]
  84. Shih, C.M.; Lee, Y.L.; Chiou, H.L.; Hsu, W.F.; Chen, W.E.; Chou, M.C.; Lin, L.Y. The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer 2005, 50, 291–297. [Google Scholar] [CrossRef] [PubMed]
  85. Pooja, S.; Chaudhary, P.; Nayak, L.V.; Rajender, S.; Saini, K.S.; Deol, D.; Kumar, S.; Bid, H.K.; Konwar, R. Polymorphic variations in IL-1beta, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women. Cytokine 2012, 60, 122–128. [Google Scholar] [CrossRef]
  86. Havranek, E.; Howell, W.M.; Fussell, H.M.; Whelan, J.A.; Whelan, M.A.; Pandha, H.S. An interleukin-10 promoter polymorphism may influence tumor development in renal cell carcinoma. J. Urol. 2005, 173, 709–712. [Google Scholar] [CrossRef]
  87. Romero, J.M.; Saenz-Lopez, P.; Cozar, J.M.; Carretero, R.; Canton, J.; Vazquez, F.; Concha, A.; Tallada, M.; Garrido, F.; Ruiz-Cabello, F. A polymorphism in the interleukin-10 promoter affects the course of disease in patients with clear-cell renal carcinoma. Hum. Immunol. 2009, 70, 60–64. [Google Scholar] [CrossRef] [PubMed]
  88. Khorrami, S.; Zamani, H.; Hasanzadeh, M.; Mehramiz, M.; Soleimani, A.; Zare Marzouni, H.; Ferns, G.A.; Esmaeili, H.; Avan, A. Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer. Gene 2022, 807, 145933. [Google Scholar] [CrossRef]
  89. Pratap, P.D.; Raza, S.T.; Zaidi, G.; Kunwar, S.; Ahmad, S.; Charles, M.R.; Eba, A.; Rajput, M. Genetic Variants in Interleukin-10 Gene Association with Susceptibility and Cervical Cancer Development: A Case Control Study. Glob. Med. Genet. 2022, 9, 129–140. [Google Scholar] [CrossRef]
  90. Nedoszytko, B.; Olszewska, B.; Roszkiewicz, J.; Glen, J.; Zablotna, M.; Lugowska-Umer, H.; Nowicki, R.; Sokolowska-Wojdylo, M. The role of polymorphism of interleukin-2, -10, -13 and TNF-alpha genes in cutaneous T-cell lymphoma pathogenesis. Adv. Dermatol. Allergol./Postępy Dermatol. Alergol. 2016, 33, 429–434. [Google Scholar] [CrossRef]
  91. Dai, Z.M.; He, A.L.; Zhang, W.G.; Liu, J.; Cao, X.M.; Chen, Y.X.; Ma, X.R.; Zhao, W.H.; Dai, Z.J. Association of the four common polymorphisms in interleukin-10 (rs1800890, rs1800896, rs1800871, and rs1800872) with non-Hodgkin’s lymphoma risk: A meta-analysis. Int. J. Clin. Exp. Med. 2014, 7, 4720–4733. [Google Scholar] [PubMed]
  92. Ovsepyan, V.A.; Gabdulkhakova, A.; Shubenkiva, A.A.; Zotina, E.N. Role of Interleukin-10 Gene Promoter Region Polymorphism in the Development of Chronic Lymphoid Leukemia. Bull. Exp. Biol. Med. 2015, 160, 275–277. [Google Scholar] [CrossRef] [PubMed]
  93. El Baiomy, M.A.; Akl, T.; ElMenshawy, N.; El-Sebaie, A.H.; Morkos, H.; El-Ashwah, S.; El-Sabbagh, A.M.; Wahba, Y.; El-Ghonemy, M. The prognostic values of the IL-10 (G1082A) and TNF-alpha (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single-center study. Indian J. Cancer 2023, 60, 217–223. [Google Scholar] [CrossRef] [PubMed]
  94. Martinez-Campos, C.; Torres-Poveda, K.; Camorlinga-Ponce, M.; Flores-Luna, L.; Maldonado-Bernal, C.; Madrid-Marina, V.; Torres, J. Polymorphisms in IL-10 and TGF-beta gene promoter are associated with lower risk to gastric cancer in a Mexican population. BMC Cancer 2019, 19, 453. [Google Scholar] [CrossRef]
  95. Xue, H.; Lin, B.; An, J.; Zhu, Y.; Huang, G. Interleukin-10-819 promoter polymorphism in association with gastric cancer risk. BMC Cancer 2012, 12, 102. [Google Scholar] [CrossRef] [PubMed]
  96. Chang, W.S.; Liao, C.H.; Tsai, C.W.; Hu, P.S.; Wu, H.C.; Hsu, S.W.; Ji, H.X.; Hsiao, C.L.; Bau, D.T. The Role of IL-10 Promoter Polymorphisms in Renal Cell Carcinoma. Anticancer Res. 2016, 36, 2205–2209. [Google Scholar] [PubMed]
  97. Hsia, T.C.; Chang, W.S.; Liang, S.J.; Chen, W.C.; Tu, C.Y.; Chen, H.J.; Yang, M.D.; Tsai, C.W.; Hsu, C.M.; Tsai, C.H.; et al. Interleukin-10 (IL-10) promoter genotypes are associated with lung cancer risk in Taiwan males and smokers. Anticancer Res. 2014, 34, 7039–7044. [Google Scholar] [PubMed]
  98. Bai, C.Y.; Shi, X.Y.; He, J.; Xue, J.; Feng, Y. Association between IL-10 genetic variations and cervical cancer susceptibility in a Chinese population. Genet. Mol. Res. 2016, 15, gmr.15038116. [Google Scholar] [CrossRef] [PubMed]
  99. Ahirwar, D.; Mandhani, A.; Mittal, R.D. Interleukin-10 G-1082A and C-819T polymorphisms as possible molecular markers of urothelial bladder cancer. Arch. Med. Res. 2009, 40, 97–102. [Google Scholar] [CrossRef]
  100. Fei, C.; Yao, X.M.; Sun, Y.; Gu, X.Z.; Yu, L.Q.; Lai, X. Interleukin-10 polymorphisms associated with susceptibility to acute myeloid leukemia. Genet. Mol. Res. 2015, 14, 925–930. [Google Scholar] [CrossRef] [PubMed]
  101. Singh, P.K.; Ahmad, M.K.; Kumar, V.; Gupta, R.; Kohli, M.; Jain, A.; Mahdi, A.A.; Bogra, J.; Chandra, G. Genetic polymorphism of interleukin-10 (-A592C) among oral cancer with squamous cell carcinoma. Arch. Oral. Biol. 2017, 77, 18–22. [Google Scholar] [CrossRef] [PubMed]
  102. Sun, J.M.; Li, Q.; Gu, H.Y.; Chen, Y.J.; Wei, J.S.; Zhu, Q.; Chen, L. Interleukin 10 rs1800872 T>G polymorphism was associated with an increased risk of esophageal cancer in a Chinese population. Asian Pac. J. Cancer Prev. 2013, 14, 3443–3447. [Google Scholar] [CrossRef]
  103. Qi, M.; Liu, D.M.; Pan, L.L.; Lin, Y.X. Interleukin-10 gene -592C>A polymorphism and susceptibility to gastric cancer. Genet. Mol. Res. 2014, 13, 8954–8961. [Google Scholar] [CrossRef] [PubMed]
  104. Gallegos-Arreola, M.P.; Zuniga Gonzalez, G.M.; Figuera, L.E.; Puebla-Perez, A.M.; Delgado Saucedo, J.I. Association of the IL-10 gene rs1800872 (-592 C>A) polymorphism with breast cancer in a Mexican population. JBUON 2019, 24, 2369–2376. [Google Scholar]
  105. Du, G.H.; Wang, J.K.; Richards, J.R.; Wang, J.J. Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer. Int. Immunopharmacol. 2019, 66, 154–161. [Google Scholar] [CrossRef] [PubMed]
  106. Duvlis, S.; Dabeski, D.; Noveski, P.; Ivkovski, L.; Plaseska-Karanfilska, D. Association of IL-10 (rs1800872) and IL-4R (rs1805010) polymorphisms with cervical intraepithelial lesions and cervical carcinomas. JBUON 2020, 25, 132–140. [Google Scholar]
  107. Gaiolla, R.D.; Moraes, M.P.T.; de Oliveira, D.E. SNPs in genes encoding for IL-10, TNF-alpha, and NFkappaB p105/p50 are associated with clinical prognostic factors for patients with Hodgkin lymphoma. PLoS ONE 2021, 16, e0248259. [Google Scholar] [CrossRef]
  108. Saraiva, M.; Vieira, P.; O’Garra, A. Biology and therapeutic potential of interleukin-10. J. Exp. Med. 2020, 217, e20190418. [Google Scholar] [CrossRef]
  109. Wang, X.; Wong, K.; Ouyang, W.; Rutz, S. Targeting IL-10 Family Cytokines for the Treatment of Human Diseases. Cold Spring Harb. Perspect. Biol. 2019, 11, a028548. [Google Scholar] [CrossRef]
  110. Hagenbaugh, A.; Sharma, S.; Dubinett, S.M.; Wei, S.H.; Aranda, R.; Cheroutre, H.; Fowell, D.J.; Binder, S.; Tsao, B.; Locksley, R.M.; et al. Altered immune responses in interleukin 10 transgenic mice. J. Exp. Med. 1997, 185, 2101–2110. [Google Scholar] [CrossRef]
  111. Loser, K.; Apelt, J.; Voskort, M.; Mohaupt, M.; Balkow, S.; Schwarz, T.; Grabbe, S.; Beissert, S. IL-10 controls ultraviolet-induced carcinogenesis in mice. J. Immunol. 2007, 179, 365–371. [Google Scholar] [CrossRef]
  112. Ruffell, B.; Chang-Strachan, D.; Chan, V.; Rosenbusch, A.; Ho, C.M.; Pryer, N.; Daniel, D.; Hwang, E.S.; Rugo, H.S.; Coussens, L.M. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 2014, 26, 623–637. [Google Scholar] [CrossRef]
  113. Sullivan, K.M.; Jiang, X.; Guha, P.; Lausted, C.; Carter, J.A.; Hsu, C.; Labadie, K.P.; Kohli, K.; Kenerson, H.L.; Daniel, S.K.; et al. Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases. Gut 2023, 72, 325–337. [Google Scholar] [CrossRef]
  114. Labadie, K.P.; Kreuser, S.A.; Brempelis, K.J.; Daniel, S.K.; Jiang, X.; Sullivan, K.M.; Utria, A.F.; Kenerson, H.L.; Kim, T.S.; Crane, C.A.; et al. Production of an interleukin-10 blocking antibody by genetically engineered macrophages increases cancer cell death in human gastrointestinal tumor slice cultures. Cancer Gene Ther. 2023, 30, 1227–1233. [Google Scholar] [CrossRef]
  115. Naing, A.; Papadopoulos, K.P.; Autio, K.A.; Ott, P.A.; Patel, M.R.; Wong, D.J.; Falchook, G.S.; Pant, S.; Whiteside, M.; Rasco, D.R.; et al. Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors. J. Clin. Oncol. 2016, 34, 3562–3569. [Google Scholar] [CrossRef] [PubMed]
  116. Porcaro, A.B.; Bianchi, A.; Gallina, S.; Panunzio, A.; Serafin, E.; Mazzucato, G.; Orlando, R.; Montanaro, F.; Patuzzo, G.M.; Baielli, A.; et al. Advanced age is an independent prognostic factor of disease progression in high-risk prostate cancer: Results in 180 patients treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection in a tertiary referral center. Aging. Clin. Exp. Res. 2023, 35, 1881–1889. [Google Scholar] [CrossRef]
  117. Defever, K.; Platz, E.A.; Lopez, D.S.; Mondul, A.M. Differences in the prevalence of modifiable risk and protective factors for prostate cancer by race and ethnicity in the National Health and Nutrition Examination Survey. Cancer Causes Control 2020, 31, 851–860. [Google Scholar] [CrossRef] [PubMed]
  118. Stone, S.N.; Hoffman, R.M.; Tollestrup, K.; Stidley, C.A.; Witter, J.L.; Gilliland, F.D. Family history, Hispanic ethnicity, and prostate cancer risk. Ethn. Dis. 2003, 13, 233–239. [Google Scholar] [PubMed]
  119. Huang, J.; Sun, J.; Wang, K.; Zheng, L.; Fan, Y.; Qian, B. Causal relationship between prostatic diseases and prostate cancer: A mendelian randomization study. BMC Cancer 2024, 24, 774. [Google Scholar] [CrossRef] [PubMed]
  120. Di Maso, M.; Augustin, L.S.A.; Jenkins, D.J.A.; Carioli, G.; Turati, F.; Grisoni, B.; Crispo, A.; La Vecchia, C.; Serraino, D.; Polesel, J. Adherence to a cholesterol-lowering diet and the risk of prostate cancer. Food Funct. 2022, 13, 5730–5738. [Google Scholar] [CrossRef]
  121. Ellis, E.T.; Fairman, B.J.; Stahr, S.D.; Bensen, J.T.; Mohler, J.L.; Song, L.; Butler, E.N.; Su, L.J.; Hsu, P.C. Cigarette smoking and prostate cancer aggressiveness among African and European American men. Cancer Causes Control 2024. [Google Scholar] [CrossRef] [PubMed]
  122. Brookman-May, S.D.; Campi, R.; Henriquez, J.D.S.; Klatte, T.; Langenhuijsen, J.F.; Brausi, M.; Linares-Espinos, E.; Volpe, A.; Marszalek, M.; Akdogan, B.; et al. Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and Progression: A Systematic Review of the Literature by the European Association of Urology Section of Oncological Urology (ESOU). Eur. Urol. Focus 2019, 5, 756–787. [Google Scholar] [CrossRef] [PubMed]
  123. Al-Fayez, S.; El-Metwally, A. Cigarette smoking and prostate cancer: A systematic review and meta-analysis of prospective cohort studies. Tob. Induc. Dis. 2023, 21, 19. [Google Scholar] [CrossRef] [PubMed]
  124. Cui, H.; Zhang, W.; Zhang, L.; Qu, Y.; Xu, Z.; Tan, Z.; Yan, P.; Tang, M.; Yang, C.; Wang, Y.; et al. Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses. PLoS Med. 2024, 21, e1004362. [Google Scholar] [CrossRef] [PubMed]
Life 14 01035 g001
Figure 1. Physical map for IL-10 rs1800896, rs3021097, and rs1800872 promoter polymorphic sites.
Figure 1. Physical map for IL-10 rs1800896, rs3021097, and rs1800872 promoter polymorphic sites.
Life 14 01035 g001
Table 1. Demographics of prostate cancer cases and control subjects.
Table 1. Demographics of prostate cancer cases and control subjects.
CharacteristicsControls (n = 436)Cases (n = 218)p-Value
n%Mean ± SDn%Mean ± SD
Age (years) 63.9 ± 6.6 63.6 ± 6.90.58 a
   <5527563.1% 14265.1% 0.67 b
   >5516136.9% 7634.9%
Smoking behavior
   Ever smoker33677.0% 17781.2% 0.27 b
   Non-smoker10023.0% 4118.8%
Family history
   First degree (father, brother, and/or son) 177.8%
   Second degree 41.8%
   No history 19790.4%
Disease stage
   Early stage 15571.1%
   Late stage 6328.9%
Pathologic grade
   Well-differentiated 2812.9%
   Moderately differentiated 8940.8%
   Poorly differentiated 10146.3%
SD: standard deviation; a based on unpaired Student’s t-test; b based on Chi-square test.
Table 2. The primer sequences, polymerase chain reaction, and restriction fragment length polymorphism methodology for identifying interleukin-10 rs1800896, rs3021097, and rs1800872 genotypes.
Table 2. The primer sequences, polymerase chain reaction, and restriction fragment length polymorphism methodology for identifying interleukin-10 rs1800896, rs3021097, and rs1800872 genotypes.
Polymorphic Cites
(rs Numbers)		Primer SequencesEndonucleasePolymorphic PatternDigested Adduct Size (bp)
A-1082G (rs1800896)F: 5′-CTCGCTGCAACCCAACTGGC-3′
R: 5′-TCTTACCTATCCCTACTTCC-3′		Mnl IA
G		139
106 + 33
T-819C (rs3021097)F: 5′-TCATTCTATGTGCTGGAGAT-3′
R: 5′-TGGGGGAAGTGGGTAAGAGT-3′		Mae IIIT
C		209
125 + 84
A-592C (rs1800872)F: 5′-GGTGAGCACTACCTGACTAG-3′
R: 5′-CCTAGGTCACAGTGACGTGG-3′		Rsa IC
A		412
236 + 176
F and R stands for forward and reverse primers, respectively.
Table 3. Distributions of interleukin-10 genotypic frequencies among prostate cancer patients and healthy controls.
Table 3. Distributions of interleukin-10 genotypic frequencies among prostate cancer patients and healthy controls.
Cases (%)Controls (%)OR (95% CI)Adjusted OR (95% CI) ap-Value b
rs1800896
   AA154 (70.6)330 (75.7)1.00 (reference)1.00 (reference)
   AG54 (24.8)96 (22.0)1.20 (0.82–1.77)1.18 (0.79–1.68)0.3933
   GG10 (4.6)10 (2.3)2.14 (0.87–5.26)1.98 (0.85–3.75)0.1451
   AG+GG64 (29.4)106 (24.3)1.29 (0.90–1.86)1.27 (0.89–1.84)0.1962
Ptrend 0.1755
PHWE 0.3428
rs3021097
   TT116 (53.2)243 (55.7)1.00 (reference)1.00 (reference)
   TC84 (38.5)159 (36.5)1.10 (0.78–1.56)1.07 (0.73–1.38)0.6253
   CC18 (8.3)34 (7.8)1.11 (0.60–2.05)1.09 (0.70–1.48)0.8627
   TC+CC102 (46.8)193 (44.3)1.11 (0.80–1.53)1.09 (0.74–1.39)0.5976
Ptrend 0.8296
PHWE 0.2680
rs1800872
   AA126 (57.8)267 (61.2)1.00 (reference)1.00 (reference)
   AC78 (35.8)146 (33.5)1.13 (0.80–1.60)1.09 (0.78–1.57)0.5406
   CC14 (6.4)23 (5.3)1.29 (0.64–2.59)1.27 (0.61–2.46)0.5938
   AC+CC92 (42.2)169 (38.8)1.15 (0.83–1.61)1.11 (0.81–1.58)0.4459
Ptrend 0.6547
PHWE 0.6034
OR: odds ratio; CI: confidence interval; a data based on Chi-square test with Yates’ correction; b adjusted for age; Ptrend: p-value based on trend analysis; PHWE: p-value based on Hardy–Weinberg Equilibrium.
Table 4. Distributions of allelic frequencies for interleukin-10 polymorphisms in prostate cancer patients and control groups.
Table 4. Distributions of allelic frequencies for interleukin-10 polymorphisms in prostate cancer patients and control groups.
Polymorphic Site
Allele		Cases (%)
N = 436		Controls (%)
N = 872		OR (95% CI)p-Value a
rs1800896
   A362 (83.0)756 (86.7)1.00 (reference)
   G 74 (17.0)116 (13.3)1.33 (0.97–1.83)0.0906
rs3021097
   T316 (72.5)645 (74.0)1.00 (reference)
   C120 (27.5)227 (26.0)1.08 (0.83–1.40)0.6106
rs1800872
   A330 (75.7)680 (78.0)1.00 (reference)
   C106 (24.3)192 (22.0)1.14 (0.87–1.49)0.3885
OR, odds ratio; CI, confidence interval. a p-value based on Chi-square test with Yate’s correction.
Table 5. Association of interleukin-10 rs1800896 genotypes with prostate cancer risk stratified by clinicopathologic characteristics.
Table 5. Association of interleukin-10 rs1800896 genotypes with prostate cancer risk stratified by clinicopathologic characteristics.
Controls (%)Cases (%)OR (95% CI)Adjusted OR (95% CI) ap-Value b
Age
   <55 (years)
      AA211 (76.7)106 (74.7)1.00 (reference)1.00 (reference)
      AG59 (21.4)32 (22.5)1.08 (0.66–1.76)1.07 (0.63–1.68)0.8563
      GG5 (1.8)4 (2.8)1.59 (0.42–6.05)1.52 (0.32–5.74)0.7405
   ≥55 (years)
      AA119 (73.9)48 (63.2)1.00 (reference)1.00 (reference)
      AG37 (23.0)22 (28.9)1.47 (0.79–2.75)1.41 (0.73–2.38)0.2907
      GG5 (3.1)6 (7.9)2.97 (0.87–10.21)2.58 (0.56–8.74)0.1430
Smoking behaviors
   Non-smokers
      AA70 (70.0)34 (82.9)1.00 (reference)1.00 (reference)
      AG25 (25.0)6 (14.7)0.49 (0.19–1.32)0.44 (0.18–1.28)0.2288
      GG5 (5.0)1 (2.4)0.41 (0.05–3.66)0.39 (0.05–3.58)0.6624
   Smokers
      AA260 (77.4)120 (67.8)1.00 (reference)1.00 (reference)
      AG71 (21.1)48 (27.1)1.46 (0.96–2.24)1.38 (0.89–2.08)0.0983
      GG5 (1.5)9 (5.1)3.90 (1.28–11.89)3.67 (1.25–8.75)0.0231
Disease stages
   Early stage
      AA330 (75.7)118 (76.1)1.00 (reference)1.00 (reference)
      AG96 (22.0)34 (21.9)0.99 (0.64–1.54)1.03 (0.71–1.62)0.9663
      GG10 (2.3)3 (2.0)0.84 (0.23–3.10)0.91 (0.19–3.25)1.0000
   Late stage
      AA330 (75.7)36 (57.1)1.00 (reference)1.00 (reference)
      AG96 (22.0)20 (31.8)1.90 (1.05–3.45)1.92 (1.09–3.68)0.0452
      GG10 (2.3)7 (11.1)6.42 (2.30–17.89)5.81 (2.54–14.77)0.0003
OR, odds ratio; CI, confidence interval. a Based on Chi-square test with Yate’s correction (all n ≥ 5) or Fisher’s exact test (any n < 5); b adjusted for other factors (age, smoking, or stage); Ptrend: p-value based on trend analysis; PHWE: p-value based on Hardy–Weinberg equilibrium; Bolded, statistically significant.
Table 6. Concise summary of the literature for association between interleukin-10 rs1800896 genotypes and prostate cancer.
Table 6. Concise summary of the literature for association between interleukin-10 rs1800896 genotypes and prostate cancer.
AuthorYearCountryEthnicsSOCControls
(GG, AG, AA)		Cases
(GG, AG, AA)		Association Highlights
Chin2024TaiwanEast AsianHB10:96:33010:54:154No association
Winchester2017USACaucasianPB140:254:134136:305:179No association
Dluzniewski2012USAMixedPB104:242:112100:212:146A allele is risky
Vancleave2010USAMixedPB288:280:9275:95:22No association
Liu2010ChinaEast AsianPB4:36:2223:27:240No association
Wang2009USACaucasianPB56:130:6983:117:57A allele is protective
Zabaleta2008USACaucasianHB86:206:102126:239:110No association
Faupel-Badger2008USACaucasianPB85:251:17373:194:115No association
Michaud2006USAMixedPB290:599:356383:857:523No association
Xu2005SwedenCaucasianPB306:689:388187:390:203No association
McCarron2002UKCaucasianPB56:113:7857:120:46A allele is protective
SOC: source of controls; PB: population based; HB: hospital based.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Chin, Y.-T.; Tsai, C.-L.; Ma, H.-H.; Cheng, D.-C.; Tsai, C.-W.; Wang, Y.-C.; Shih, H.-Y.; Chang, S.-Y.; Gu, J.; Chang, W.-S.; et al. Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer. Life 2024, 14, 1035. https://doi.org/10.3390/life14081035

AMA Style

Chin Y-T, Tsai C-L, Ma H-H, Cheng D-C, Tsai C-W, Wang Y-C, Shih H-Y, Chang S-Y, Gu J, Chang W-S, et al. Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer. Life. 2024; 14(8):1035. https://doi.org/10.3390/life14081035

Chicago/Turabian Style

Chin, Yu-Ting, Chung-Lin Tsai, Hung-Huan Ma, Da-Chuan Cheng, Chia-Wen Tsai, Yun-Chi Wang, Hou-Yu Shih, Shu-Yu Chang, Jian Gu, Wen-Shin Chang, and et al. 2024. "Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer" Life 14, no. 8: 1035. https://doi.org/10.3390/life14081035

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop