The interaction of genetic and environmental factors can determine individual susceptibility to v... more The interaction of genetic and environmental factors can determine individual susceptibility to various cancers. We studied the influence of NAT2 and codon 72 p53 polymorphisms on 151 patients with lung cancer and an equal number of matched population controls. Polymorphisms of NAT2 and p53 were determined by PCR-RFLP techniques. The results were analyzed using logistic regression analysis. A statistically significant relationship between NAT2*5 and NAT2*6 alleles and lung cancer risk was observed. In addition, the population with slow acetylator alleles for NAT2*5 and NAT2*6 had a significantly higher risk of lung cancer compared with rapid acetylator alleles both in smokers and nonsmokers. The combined genotype of heterozygous arginine (Arg)/proline (Pro), Pro/Pro, and slow acetylator alleles of NAT2*5 and NAT2*6 showed higher, although not significant, risk of lung cancer compared with Arg/Arg and rapid acetylator alleles of NAT2*5 and NAT2*6. In conclusion, these findings suggest that the influence of NAT2 genotype, alone or in combination with p53 genotype, may confer increased susceptibility to lung cancer.
Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the t... more Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G-->A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92-3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03-3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.
Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected... more Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conj... more Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.
XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementin... more XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction–restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12–0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007–0.605, P = 0.03), whereas ERCC2 (Lys/Gln–Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46–9.44). Upon analysis of gene–gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln–Gln/Gln)–ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09–1.16) and XRCC1 (Gln/Gln)–ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11–1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC.
DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyze... more DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyzes the formation of a phosphodiester bond at a nick junction on single- and double-strand breaks. We have conducted a hospital-based case-control study to examine the role of polymorphism of DNA repair gene ligase I (LIGI) in the context of lung cancer risk for north Indian population. One hundred, fifty-one primary lung cancer cases and an equal number of matching hospital controls were collected. The LIGI polymorphism was determined by using the PCR-RFLP method. The association between polymorphisms in the LIGI gene with the risk of lung cancer was estimated by computing odds ratios (ORs) and a 95% confidence interval (CI) using a Multivariate Logistic Regression Analysis. The risk for lung cancer was not associated for individuals featuring LIGI (AC) (OR -0.8, 95% CI = 0.44-1.40) and (AA) (OR -0.8, 95% CI = 0.41-1.80) genotypes. The DNA repair gene (LIGI) may not be playing an important role in modulating the risk of lung cancer in the north Indian population.
Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patter... more Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patterns of metastasis, and response to therapy. It arises from a complex etiology that involves both exogenous (diet, environment, etc.) and endogenous (hormonal and genetic) factors. The present study was performed to explore the role of various genotypes involved in steroid metabolism and synthesis in the causation of prostate cancer. Genetic polymorphism of the ER, CYP17, SRD5A2 (TA repeats), and PSA genes were analyzed in 157 cases of prostate cancer and 340 controls [170 healthy males and 170 patients of benign prostate hyperplasia (BPH)]. Mutant genotypes of ER and CYP17 showed 2- and 3- and 3.5-fold increased risk of prostate cancer, respectively, as compared to BPH and healthy controls. Interaction of mutant (homozygous and heterozygous) alleles of CYP17 with TA (0/0) led to a twofold increased risk of prostate cancer. Risk was more than twofold with the combination of mutant alleles of ER and CYP17. The PSA gene polymorphism did not show any increased risk of prostate cancer. This indicates the role of mutant allele of ER and CYP17 in the development and progression of prostate cancer and rules out any increased risk with PSA polymorphism in the north Indian population.
The purpose of this study was to analyse the frequency and type of mutations in the coding region... more The purpose of this study was to analyse the frequency and type of mutations in the coding region of androgen receptor (AR) and to determine the role of polymorphisms in the intron 1 of ERα, exon 5 of ERβ, intron 7 of progesterone, exon 7 of the aromatase (CYP19) and exon 9 of VDR genes in the risk of prostate cancer. PCR-RFLP analysis of all above the genes was on 100 prostate cancer patients and an equal number of matching controls. The study also included PCR-SSCP analyses of exons 2–8 of AR gene. The genotype containing −/− allele of ERα gene was statistically significant for the risk of prostate cancer pose (OR, 2.70; 95% CI, 1.08–6.70, P = 0.032) Rr genotype of ERβ gene also have a higher risk (OR, 1.65; 95% CI, 0.52–5.23) for prostate cancer. The Cys allele of CYP19 gene was also associated with statistically significant increased risk of prostate cancer (OR; 2.28, 95% CI, 1.20–4.35, P = 0.012). tt genotype of codon 352 of VDR gene showed an OR of 0.43 for (95% CI, 0.13–1.39) and an OR for Tt genotype was 0.65 (95% CI, 0.36–1.16). Taken together, the results showed that in North Indian population, ERα and CYP19 genes may be playing a role in the risk of prostate cancer.
DNA repair forms the most effective defense system against DNA damage. The XRCC1 gene product is ... more DNA repair forms the most effective defense system against DNA damage. The XRCC1 gene product is implicated in single-strand and base-excision repair mechanisms. Our main aim was to investigate the relationship between the XRCC1 gene with lung cancer on the north-Indian population. Blood samples from 225 North-Indian subjects including 103 newly diagnosed cases and 122 population-based healthy persons were collected. XRCC1 genotypes were detected using a PCR-RFLP technique. The data were analyzed by logistic regression analysis. XRCC1 polymorphisms at codon 399 were found to be protective in the development of lung cancer (OR--0.6, 95% CI--0.46-0.80, p-0.0008). The codon 194 Trp/Trp genotype was associated with a slightly increased risk of lung cancer. When assessed in nonsmokers, only the Arg/Trp genotype of XRCC1 codon 194 was positively associated with lung cancer (OR--2.3, 95% CI--0.77-7.20). Smoking also seemed to significantly interact with the combined genotypes of XRCC1 codon 399 Arg/Gln/Gln/Gln. In conclusion, the results have suggested that the XRCC1 gene might be the risk genotype for lung cancer in this population.
Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequen... more Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequency of >1% in the population. This genetic variability (polymorphisms) can be a factor in cancer risk. The functional polymorphisms in GST genes play an important role in susceptibility to lung cancer. In our previous study, we reported that the combination of certain genotypes of GSTM1, GSTT1 and CYP1A1 is associated with lung cancer. The study has been extended to investigate the potential role of polymorphism in GSTP1 alone or in combination with the status of GSTM1 and GSTT1 genes in the likelihood of development of lung cancer. A total of 302 subjects (151 cases and 151 controls) were evaluated. Using a case-control design, individuals were genotyped for GSTs using multiplex polymerase chain reaction and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regression. The combined 'at risk' genotypes of GSTM1 null and GSTT1 null in comparison with 'wild-type' genotypes seems to be associated with a greater risk of lung cancer, but the results are not significant (odds ratio (OR) 2.0, 95% confidence interval (CI) 0.68-5.96) and for squamous cell carcinoma (SqCC) it was 1.6-fold (OR 1.6, 95% CI 0.49-5.68). In summary, our case-control study of lung cancer revealed that the effect of these polymorphisms is not very marked for different genotypic combinations of GSTP1, GSTM1 and GSTT1 in the context of developing lung cancer in a north Indian population. However, the increased risk was limited to SqCC, and was not found for other histological subtypes. Further analyses on this topic are needed.
International Journal of Gynecology & Obstetrics, 2008
To determine whether a polymorphism at position + 3953 in exon 5 of the lL-1β gene (IL-1β + 3953)... more To determine whether a polymorphism at position + 3953 in exon 5 of the lL-1β gene (IL-1β + 3953), a condition associated with an increased risk for a number of inflammatory diseases, is also involved in the development of cervical cancer.We isolated DNA from peripheral blood in 150 women with cervical cancer and 200 healthy controls, and IL-1β + 3953 allele polymorphism was determined by polymerase chain reaction.Genotypes A1/A2 and A2/A2 + A1/A2 were associated with increased risk of cervical cancer (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.78–4.67; P < 0.001 and OR, 2.85; 95% CI, 1.77–4.6; P < 0.001, respectively). The risk in a passive smoker with A2/A2 or A1/A2 genotype was increased more than 5-fold (OR, 5.69; 95% CI, 2.61–12.50; P < 0.001) compared with a nonsmoker with the A1/A1 genotype.This study provides evidence of an association between lL-1β + 3953 polymorphism and risk of cervical cancer.
The interaction of genetic and environmental factors can determine individual susceptibility to v... more The interaction of genetic and environmental factors can determine individual susceptibility to various cancers. We studied the influence of NAT2 and codon 72 p53 polymorphisms on 151 patients with lung cancer and an equal number of matched population controls. Polymorphisms of NAT2 and p53 were determined by PCR-RFLP techniques. The results were analyzed using logistic regression analysis. A statistically significant relationship between NAT2*5 and NAT2*6 alleles and lung cancer risk was observed. In addition, the population with slow acetylator alleles for NAT2*5 and NAT2*6 had a significantly higher risk of lung cancer compared with rapid acetylator alleles both in smokers and nonsmokers. The combined genotype of heterozygous arginine (Arg)/proline (Pro), Pro/Pro, and slow acetylator alleles of NAT2*5 and NAT2*6 showed higher, although not significant, risk of lung cancer compared with Arg/Arg and rapid acetylator alleles of NAT2*5 and NAT2*6. In conclusion, these findings suggest that the influence of NAT2 genotype, alone or in combination with p53 genotype, may confer increased susceptibility to lung cancer.
Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the t... more Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G→A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92–3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03–3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.
Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected... more Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conj... more Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.
The interaction of genetic and environmental factors can determine individual susceptibility to v... more The interaction of genetic and environmental factors can determine individual susceptibility to various cancers. We studied the influence of NAT2 and codon 72 p53 polymorphisms on 151 patients with lung cancer and an equal number of matched population controls. Polymorphisms of NAT2 and p53 were determined by PCR-RFLP techniques. The results were analyzed using logistic regression analysis. A statistically significant relationship between NAT2*5 and NAT2*6 alleles and lung cancer risk was observed. In addition, the population with slow acetylator alleles for NAT2*5 and NAT2*6 had a significantly higher risk of lung cancer compared with rapid acetylator alleles both in smokers and nonsmokers. The combined genotype of heterozygous arginine (Arg)/proline (Pro), Pro/Pro, and slow acetylator alleles of NAT2*5 and NAT2*6 showed higher, although not significant, risk of lung cancer compared with Arg/Arg and rapid acetylator alleles of NAT2*5 and NAT2*6. In conclusion, these findings suggest that the influence of NAT2 genotype, alone or in combination with p53 genotype, may confer increased susceptibility to lung cancer.
Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the t... more Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92-3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03-3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.
Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected... more Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conj... more Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.
XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementin... more XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction–restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12–0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007–0.605, P = 0.03), whereas ERCC2 (Lys/Gln–Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46–9.44). Upon analysis of gene–gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln–Gln/Gln)–ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09–1.16) and XRCC1 (Gln/Gln)–ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11–1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC.
DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyze... more DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyzes the formation of a phosphodiester bond at a nick junction on single- and double-strand breaks. We have conducted a hospital-based case-control study to examine the role of polymorphism of DNA repair gene ligase I (LIGI) in the context of lung cancer risk for north Indian population. One hundred, fifty-one primary lung cancer cases and an equal number of matching hospital controls were collected. The LIGI polymorphism was determined by using the PCR-RFLP method. The association between polymorphisms in the LIGI gene with the risk of lung cancer was estimated by computing odds ratios (ORs) and a 95% confidence interval (CI) using a Multivariate Logistic Regression Analysis. The risk for lung cancer was not associated for individuals featuring LIGI (AC) (OR -0.8, 95% CI = 0.44-1.40) and (AA) (OR -0.8, 95% CI = 0.41-1.80) genotypes. The DNA repair gene (LIGI) may not be playing an important role in modulating the risk of lung cancer in the north Indian population.
Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patter... more Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patterns of metastasis, and response to therapy. It arises from a complex etiology that involves both exogenous (diet, environment, etc.) and endogenous (hormonal and genetic) factors. The present study was performed to explore the role of various genotypes involved in steroid metabolism and synthesis in the causation of prostate cancer. Genetic polymorphism of the ER, CYP17, SRD5A2 (TA repeats), and PSA genes were analyzed in 157 cases of prostate cancer and 340 controls [170 healthy males and 170 patients of benign prostate hyperplasia (BPH)]. Mutant genotypes of ER and CYP17 showed 2- and 3- and 3.5-fold increased risk of prostate cancer, respectively, as compared to BPH and healthy controls. Interaction of mutant (homozygous and heterozygous) alleles of CYP17 with TA (0/0) led to a twofold increased risk of prostate cancer. Risk was more than twofold with the combination of mutant alleles of ER and CYP17. The PSA gene polymorphism did not show any increased risk of prostate cancer. This indicates the role of mutant allele of ER and CYP17 in the development and progression of prostate cancer and rules out any increased risk with PSA polymorphism in the north Indian population.
The purpose of this study was to analyse the frequency and type of mutations in the coding region... more The purpose of this study was to analyse the frequency and type of mutations in the coding region of androgen receptor (AR) and to determine the role of polymorphisms in the intron 1 of ERα, exon 5 of ERβ, intron 7 of progesterone, exon 7 of the aromatase (CYP19) and exon 9 of VDR genes in the risk of prostate cancer. PCR-RFLP analysis of all above the genes was on 100 prostate cancer patients and an equal number of matching controls. The study also included PCR-SSCP analyses of exons 2–8 of AR gene. The genotype containing −/− allele of ERα gene was statistically significant for the risk of prostate cancer pose (OR, 2.70; 95% CI, 1.08–6.70, P = 0.032) Rr genotype of ERβ gene also have a higher risk (OR, 1.65; 95% CI, 0.52–5.23) for prostate cancer. The Cys allele of CYP19 gene was also associated with statistically significant increased risk of prostate cancer (OR; 2.28, 95% CI, 1.20–4.35, P = 0.012). tt genotype of codon 352 of VDR gene showed an OR of 0.43 for (95% CI, 0.13–1.39) and an OR for Tt genotype was 0.65 (95% CI, 0.36–1.16). Taken together, the results showed that in North Indian population, ERα and CYP19 genes may be playing a role in the risk of prostate cancer.
DNA repair forms the most effective defense system against DNA damage. The XRCC1 gene product is ... more DNA repair forms the most effective defense system against DNA damage. The XRCC1 gene product is implicated in single-strand and base-excision repair mechanisms. Our main aim was to investigate the relationship between the XRCC1 gene with lung cancer on the north-Indian population. Blood samples from 225 North-Indian subjects including 103 newly diagnosed cases and 122 population-based healthy persons were collected. XRCC1 genotypes were detected using a PCR-RFLP technique. The data were analyzed by logistic regression analysis. XRCC1 polymorphisms at codon 399 were found to be protective in the development of lung cancer (OR--0.6, 95% CI--0.46-0.80, p-0.0008). The codon 194 Trp/Trp genotype was associated with a slightly increased risk of lung cancer. When assessed in nonsmokers, only the Arg/Trp genotype of XRCC1 codon 194 was positively associated with lung cancer (OR--2.3, 95% CI--0.77-7.20). Smoking also seemed to significantly interact with the combined genotypes of XRCC1 codon 399 Arg/Gln/Gln/Gln. In conclusion, the results have suggested that the XRCC1 gene might be the risk genotype for lung cancer in this population.
Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequen... more Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequency of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1% in the population. This genetic variability (polymorphisms) can be a factor in cancer risk. The functional polymorphisms in GST genes play an important role in susceptibility to lung cancer. In our previous study, we reported that the combination of certain genotypes of GSTM1, GSTT1 and CYP1A1 is associated with lung cancer. The study has been extended to investigate the potential role of polymorphism in GSTP1 alone or in combination with the status of GSTM1 and GSTT1 genes in the likelihood of development of lung cancer. A total of 302 subjects (151 cases and 151 controls) were evaluated. Using a case-control design, individuals were genotyped for GSTs using multiplex polymerase chain reaction and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regression. The combined &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;at risk&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; genotypes of GSTM1 null and GSTT1 null in comparison with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;wild-type&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; genotypes seems to be associated with a greater risk of lung cancer, but the results are not significant (odds ratio (OR) 2.0, 95% confidence interval (CI) 0.68-5.96) and for squamous cell carcinoma (SqCC) it was 1.6-fold (OR 1.6, 95% CI 0.49-5.68). In summary, our case-control study of lung cancer revealed that the effect of these polymorphisms is not very marked for different genotypic combinations of GSTP1, GSTM1 and GSTT1 in the context of developing lung cancer in a north Indian population. However, the increased risk was limited to SqCC, and was not found for other histological subtypes. Further analyses on this topic are needed.
International Journal of Gynecology & Obstetrics, 2008
To determine whether a polymorphism at position + 3953 in exon 5 of the lL-1β gene (IL-1β + 3953)... more To determine whether a polymorphism at position + 3953 in exon 5 of the lL-1β gene (IL-1β + 3953), a condition associated with an increased risk for a number of inflammatory diseases, is also involved in the development of cervical cancer.We isolated DNA from peripheral blood in 150 women with cervical cancer and 200 healthy controls, and IL-1β + 3953 allele polymorphism was determined by polymerase chain reaction.Genotypes A1/A2 and A2/A2 + A1/A2 were associated with increased risk of cervical cancer (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.78–4.67; P < 0.001 and OR, 2.85; 95% CI, 1.77–4.6; P < 0.001, respectively). The risk in a passive smoker with A2/A2 or A1/A2 genotype was increased more than 5-fold (OR, 5.69; 95% CI, 2.61–12.50; P < 0.001) compared with a nonsmoker with the A1/A1 genotype.This study provides evidence of an association between lL-1β + 3953 polymorphism and risk of cervical cancer.
The interaction of genetic and environmental factors can determine individual susceptibility to v... more The interaction of genetic and environmental factors can determine individual susceptibility to various cancers. We studied the influence of NAT2 and codon 72 p53 polymorphisms on 151 patients with lung cancer and an equal number of matched population controls. Polymorphisms of NAT2 and p53 were determined by PCR-RFLP techniques. The results were analyzed using logistic regression analysis. A statistically significant relationship between NAT2*5 and NAT2*6 alleles and lung cancer risk was observed. In addition, the population with slow acetylator alleles for NAT2*5 and NAT2*6 had a significantly higher risk of lung cancer compared with rapid acetylator alleles both in smokers and nonsmokers. The combined genotype of heterozygous arginine (Arg)/proline (Pro), Pro/Pro, and slow acetylator alleles of NAT2*5 and NAT2*6 showed higher, although not significant, risk of lung cancer compared with Arg/Arg and rapid acetylator alleles of NAT2*5 and NAT2*6. In conclusion, these findings suggest that the influence of NAT2 genotype, alone or in combination with p53 genotype, may confer increased susceptibility to lung cancer.
Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the t... more Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G→A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92–3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03–3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.
Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected... more Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conj... more Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.
Uploads
Papers by Pushpinder Kaur