Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its ri... more Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models’ sensitivity. All tests were 2-sided. Results The area under the curve for the protein-b...
Identification of novel risk biomarkers may enhance early detection of smoking-related lung cance... more Identification of novel risk biomarkers may enhance early detection of smoking-related lung cancer. We measured 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia.We identified 36 proteins with replicable associations with risk of imminent lung cancer diagnosis (all p<4×10-5). These included several documented tumor markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) but most had not been previously reported. The 36 proteins included several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation ranged from 1.31 for IGFBP-1 (95% CI: 1.17-1.47) to 2.43 for CEACAM5 (95% CI: 2.04-2.89). We mapped the 36 proteins to the hallmarks of cancer and found that proliferative signaling, tumor-promoting inflammat...
Background: Findings from an analysis published in 2013, using combined retrospective and prospec... more Background: Findings from an analysis published in 2013, using combined retrospective and prospective data pooled from 3 cohort studies, were consistent with tamoxifen use after 1st breast cancer (BC) being associated with reduced CBC risk for both BRCA1 and BRCA2 mutation carriers, although the analysis of prospective data alone (based on 100 incident CBCs) gave inconclusive results. The association did not differ by estrogen receptor (ER) status of the 1st BC, suggesting that tamoxifen may be a useful secondary BC prevention agent for mutation carriers regardless of the ER status of their 1st BC. The aim of this updated analysis was to assess these associations after incorporating data from an additional 1,279 mutation carriers and with further follow-up providing 153 additional prospective CBC events. Methods: Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and with no other invasive cancer or tamoxifen use before their 1st BC. They w...
Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found t... more Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-ana...
Background: Emerging evidence suggests that dietary omega-6 polyunsaturated fatty acids (n-6 PUFA... more Background: Emerging evidence suggests that dietary omega-6 polyunsaturated fatty acids (n-6 PUFA) plays a role in the primary prevention of type 2 diabetes (T2D). Aims: To evaluate the relation between blood and adipose tissue levels of n-6 PUFA and incident T2D, including n-6 linoleic acid (LA), the major dietary PUFA abundant in vegetable oils, and n-6 arachidonic acid (AA), a key precursor of endogenous metabolites that modulate glucose metabolism and inflammation. Methods: A global consortium of 20 prospective cohort studies identified by February 2016. Each study measured LA and AA at study baseline among adults>18y without prevalent T2D, and assessed the association of n-6 PUFA biomarkers and T2D risk prospectively using individual-level data, using a pre-specified analytic plan and harmonized exposures, covariates, and effect modifiers. Findings were centrally pooled using fixed-effects meta-analysis. Results: 39,740 men and women from 10 countries were included (range of...
We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related can... more We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10‐year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage‐specific frequency and quantity, was used to estimate group‐based sex‐specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol‐related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol‐related cancers were diagnosed during 485 525 person‐years in women and 789 during 303 218 ...
Multiple myeloma (MM) is the second most common hematological cancer and causes significant morta... more Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population‐based case–control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales. Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50–0.93), and there was an inverse dose–response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% C...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Background: Obesity increases the risk of 13 cancer types. Given the long process of carcinogenes... more Background: Obesity increases the risk of 13 cancer types. Given the long process of carcinogenesis, it is important to determine the impact of patterns of body mass over time. Methods: Using data from 30,377 participants in the Melbourne Collaborative Cohort Study, we identified body mass index (BMI) trajectories across adulthood and examined their association with the risk of obesity-related cancer. Participants completed interviews and questionnaires at baseline (1990–1994, age 40–69 years), follow-up 1 (1995–1998), and follow-up 2 (2003–2005). Body mass was recalled for age 18 to 21 years, measured at baseline, self-reported at follow-up 1, and measured at follow-up 2. Height was measured at baseline. Cancer diagnoses were ascertained from the Victorian Cancer Registry and the Australian Cancer Database. A latent class trajectory model was used to identify BMI trajectories that were not defined a priori. Cox regression was used to estimate HRs and 95% confidence intervals (CI) o...
PURPOSE The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-ster... more PURPOSE The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol may affect renal function. The aim of this study was to assess associations between analgesic use and risk of RCC. METHODS A population-based case-control family design was used. Cases were recruited via two Australian state cancer registries. Controls were siblings or partners of cases. Analgesic use was captured by self-completed questionnaire. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for RCC risk associated with regular analgesic use (at least 5 times per month for 6 months or more) and duration and frequency of use. RESULTS The analysis included 1064 cases and 724 controls. Regular use of paracetamol was associated with an increased risk of RCC (OR 1.41, 95%CI 1.13-1.77). Regular use of NSAIDs was associated with increased risk of RCC for women (OR 1.71, 95% CI 1.23-2.39) but not men (OR 0.83, 95% CI 0.58-1.18; p-interaction=0.003). There was no evidence of a dose-response for duration of use of paracetamol (linear trend p = 0.77) and weak evidence for non- aspirin NSAID use by women (linear trend p = 0.054). CONCLUSION This study found that regular use of paracetamol was associated with increased risk of RCC. NSAID use was associated with increased risk only for women.
5007 Background: This randomized, prospective phase III trial investigated if immediate intervent... more 5007 Background: This randomized, prospective phase III trial investigated if immediate intervention with androgen deprivation therapy (ADT) (Arm B) improved overall survival compared to delayed AD...
Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear... more Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear. Relatively few prospective studies have utilized objective omega-3 biomarkers to assess risk. Aims: To assess the prospective relationship between circulating and tissue levels of alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with respect to risk of T2D. Methods: A global consortium of 20 prospective cohort studies from 14 nations with assessments of ALA, EPA, DPA, or DHA in adults (age > 18 years) were identified through July 2017 and included in this investigation. A pre-specified analytic protocol, including definitions for exposures, covariate list, disease outcome definitions, and subgroup analyses was developed and followed in new participant-level cohort analysis. Associations were pooled using inverse variance-weighted meta-analysis. Results: Among 65,147 participants, 16,693 incident cases of T2D occurre...
Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its ri... more Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models’ sensitivity. All tests were 2-sided. Results The area under the curve for the protein-b...
Identification of novel risk biomarkers may enhance early detection of smoking-related lung cance... more Identification of novel risk biomarkers may enhance early detection of smoking-related lung cancer. We measured 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia.We identified 36 proteins with replicable associations with risk of imminent lung cancer diagnosis (all p<4×10-5). These included several documented tumor markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) but most had not been previously reported. The 36 proteins included several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation ranged from 1.31 for IGFBP-1 (95% CI: 1.17-1.47) to 2.43 for CEACAM5 (95% CI: 2.04-2.89). We mapped the 36 proteins to the hallmarks of cancer and found that proliferative signaling, tumor-promoting inflammat...
Background: Findings from an analysis published in 2013, using combined retrospective and prospec... more Background: Findings from an analysis published in 2013, using combined retrospective and prospective data pooled from 3 cohort studies, were consistent with tamoxifen use after 1st breast cancer (BC) being associated with reduced CBC risk for both BRCA1 and BRCA2 mutation carriers, although the analysis of prospective data alone (based on 100 incident CBCs) gave inconclusive results. The association did not differ by estrogen receptor (ER) status of the 1st BC, suggesting that tamoxifen may be a useful secondary BC prevention agent for mutation carriers regardless of the ER status of their 1st BC. The aim of this updated analysis was to assess these associations after incorporating data from an additional 1,279 mutation carriers and with further follow-up providing 153 additional prospective CBC events. Methods: Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and with no other invasive cancer or tamoxifen use before their 1st BC. They w...
Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found t... more Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-ana...
Background: Emerging evidence suggests that dietary omega-6 polyunsaturated fatty acids (n-6 PUFA... more Background: Emerging evidence suggests that dietary omega-6 polyunsaturated fatty acids (n-6 PUFA) plays a role in the primary prevention of type 2 diabetes (T2D). Aims: To evaluate the relation between blood and adipose tissue levels of n-6 PUFA and incident T2D, including n-6 linoleic acid (LA), the major dietary PUFA abundant in vegetable oils, and n-6 arachidonic acid (AA), a key precursor of endogenous metabolites that modulate glucose metabolism and inflammation. Methods: A global consortium of 20 prospective cohort studies identified by February 2016. Each study measured LA and AA at study baseline among adults>18y without prevalent T2D, and assessed the association of n-6 PUFA biomarkers and T2D risk prospectively using individual-level data, using a pre-specified analytic plan and harmonized exposures, covariates, and effect modifiers. Findings were centrally pooled using fixed-effects meta-analysis. Results: 39,740 men and women from 10 countries were included (range of...
We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related can... more We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10‐year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage‐specific frequency and quantity, was used to estimate group‐based sex‐specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol‐related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol‐related cancers were diagnosed during 485 525 person‐years in women and 789 during 303 218 ...
Multiple myeloma (MM) is the second most common hematological cancer and causes significant morta... more Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population‐based case–control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales. Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50–0.93), and there was an inverse dose–response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% C...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Background: Obesity increases the risk of 13 cancer types. Given the long process of carcinogenes... more Background: Obesity increases the risk of 13 cancer types. Given the long process of carcinogenesis, it is important to determine the impact of patterns of body mass over time. Methods: Using data from 30,377 participants in the Melbourne Collaborative Cohort Study, we identified body mass index (BMI) trajectories across adulthood and examined their association with the risk of obesity-related cancer. Participants completed interviews and questionnaires at baseline (1990–1994, age 40–69 years), follow-up 1 (1995–1998), and follow-up 2 (2003–2005). Body mass was recalled for age 18 to 21 years, measured at baseline, self-reported at follow-up 1, and measured at follow-up 2. Height was measured at baseline. Cancer diagnoses were ascertained from the Victorian Cancer Registry and the Australian Cancer Database. A latent class trajectory model was used to identify BMI trajectories that were not defined a priori. Cox regression was used to estimate HRs and 95% confidence intervals (CI) o...
PURPOSE The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-ster... more PURPOSE The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol may affect renal function. The aim of this study was to assess associations between analgesic use and risk of RCC. METHODS A population-based case-control family design was used. Cases were recruited via two Australian state cancer registries. Controls were siblings or partners of cases. Analgesic use was captured by self-completed questionnaire. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for RCC risk associated with regular analgesic use (at least 5 times per month for 6 months or more) and duration and frequency of use. RESULTS The analysis included 1064 cases and 724 controls. Regular use of paracetamol was associated with an increased risk of RCC (OR 1.41, 95%CI 1.13-1.77). Regular use of NSAIDs was associated with increased risk of RCC for women (OR 1.71, 95% CI 1.23-2.39) but not men (OR 0.83, 95% CI 0.58-1.18; p-interaction=0.003). There was no evidence of a dose-response for duration of use of paracetamol (linear trend p = 0.77) and weak evidence for non- aspirin NSAID use by women (linear trend p = 0.054). CONCLUSION This study found that regular use of paracetamol was associated with increased risk of RCC. NSAID use was associated with increased risk only for women.
5007 Background: This randomized, prospective phase III trial investigated if immediate intervent... more 5007 Background: This randomized, prospective phase III trial investigated if immediate intervention with androgen deprivation therapy (ADT) (Arm B) improved overall survival compared to delayed AD...
Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear... more Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear. Relatively few prospective studies have utilized objective omega-3 biomarkers to assess risk. Aims: To assess the prospective relationship between circulating and tissue levels of alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with respect to risk of T2D. Methods: A global consortium of 20 prospective cohort studies from 14 nations with assessments of ALA, EPA, DPA, or DHA in adults (age > 18 years) were identified through July 2017 and included in this investigation. A pre-specified analytic protocol, including definitions for exposures, covariate list, disease outcome definitions, and subgroup analyses was developed and followed in new participant-level cohort analysis. Associations were pooled using inverse variance-weighted meta-analysis. Results: Among 65,147 participants, 16,693 incident cases of T2D occurre...
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