Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Trajectories of body mass index from early adulthood to late midlife and incidence of total knee arthroplasty for osteoarthritis: findings from a prospective cohort study.

OBJECTIVE: To examine the association between body mass index (BMI) trajectories from early adulthood to late midlife and risk of total knee arthroplasty (TKA) for osteoarthritis. METHODS: 24,368 participants from the Melbourne Collaborative Cohort Study with weight collected during 1990-1994, 1995-1998, and 2003-2007, recalled weight at age 18-21 years, and height measured during 1990-1994 were included. Incident TKA from 2003 to 2007 to December 2018 was determined by linking cohort records to the National Joint Replacement Registry. RESULTS: Using group-based trajectory modelling, six distinct trajectories (TR) of BMI from early adulthood (age 18-21 years) to late midlife (approximately 62 years) were identified: lower normal to normal BMI (TR1; 19.7% population), normal BMI to borderline overweight (TR2; 36.7%), normal BMI to overweight (TR3; 26.8%), overweight to borderline obese (TR4; 3.5%), normal BMI to class 1 obesity (TR5; 10.1%), overweight to class 2 obesity (TR6; 3.2%). Over 12.4 years, 1,328 (5.4%) had TKA. The hazard ratios for TKA increased in all TR compared to TR1 [from TR2: 2.03 (95% CI 1.64-2.52) to TR6: 8.59 (6.44-11.46)]. 28.4% of TKA could be prevented if individuals followed the trajectory one lower, an average weight reduction of 8-12 kg from early adulthood to late midlife, saving $AUS 373 million/year. Most reduction would occur in TR2 (population attributable fraction 37.9%, 95% CI 26.7-47.3%) and TR3 (26.8%, 20.0-31.2%). CONCLUSIONS: Prevention of weight gain from young adulthood to late midlife in order to reduce overweight/obesity has the potential to significantly reduce the cost and burden of TKA.

Analgesic use and the risk of renal cell carcinoma - Findings from the Consortium for the Investigation of Renal Malignancies (CONFIRM) study.

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.

Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.

BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously. CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.

Dietary inflammatory index or Mediterranean diet score as risk factors for total and cardiovascular mortality.

BACKGROUND AND AIMS: Dietary patterns are associated with risk of cardiovascular disease (CVD). We aimed to examine associations of the Dietary Inflammatory Index (DII) and the Mediterranean Diet Score (MDS) with total, cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in the Melbourne Collaborative Cohort Study; and compare the strengths of the associations. METHODS AND RESULTS: In our prospective cohort study of 41,513 men and women aged 40-69 years, a food frequency questionnaire was completed at baseline and mortality data were obtained via linkage with local and national registries over an average of 19 years follow up. At baseline, questionnaires were completed and physical measures and blood samples taken. Cox proportional hazards models, adjusting for age, alcohol consumption, sex, region of origin, personal history of CVD or diabetes and family history of CVD, were used to assess associations between dietary scores and mortality. More Mediterranean or less inflammatory diets were associated with lower total, CVD and CHD mortality. The hazard ratio for total mortality comparing the highest and lowest quintiles was 1.16 (95%CI: 1.08-1.24) for DII; and 0.86 (95%CI: 0.80-0.93) comparing the highest and lowest three categories of MDS. Using the Bayesian information criterion, there was no evidence that the DII score was more strongly associated with total and CVD mortality than was the MDS. CONCLUSIONS: The MDI and the DII show similar associations with total and cardiovascular mortality, consistent with the consensus that plant-based diets are beneficial for health.

Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

Age-related macular degeneration and mortality: the Melbourne Collaborative Cohort Study.

AimsTo assess associations between features of age-related macular degeneration (AMD) and mortality.MethodsA total of 21 129 participants from the Melbourne Collaborative Cohort Study aged 47-85 years (60% female) were assessed for AMD (2003-2007). Mortality data to December 31, 2012 were obtained through linkage with the National Death Index. Associations were assessed using Cox regression, adjusting for age, sex, smoking, region of birth, education, physical activity, diet and alcohol.ResultsLate AMD was identified in 122 (0.6%) participants, including those with choroidal neovascularisation (n=55, 0.3%), geographic atrophy (n=87, 0.4%) and reticular pseudodrusen (n=87, 0.4%). After a median follow-up period of 8.1 years, 1669 (8%) participants had died, including those from cardiovascular diseases (386), tobacco-related cancers (179), and neurodegenerative disease (157). There was evidence of an increased rate of all-cause mortality for those with choroidal neovascularisation (Hazard Ratio (HR) 1.71 95% CI 1.06-2.76) and geographic atrophy (HR 1.46 95% CI 0.99-2.16). Choroidal neovascularisation was also associated with an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15) and geographic atrophy was associated with an increased rate of death from tobacco-related cancer (HR 2.86 95% CI 1.15-7.09). Weak evidence was also present for an association between choroidal neovascularisation and death from neurodegenerative disease (HR 2.49 95% CI 0.79-7.85). Neither reticular pseudodrusen nor the earlier stages of AMD were associated with mortality.ConclusionsLate AMD is associated with an increased rate of all-cause mortality. Choroidal neovascularisation and geographic atrophy were associated with death from cardiovascular disease and tobacco-related cancer, respectively.

Associations between hip bone mineral density, aortic calcification and cardiac workload in community-dwelling older Australians.

In older adults, lower bone density in the proximal femur was associated with increased heart burden, and this association was linked to calcification in the aorta. These results were seen in women but not in men. PURPOSE: To determine whether there is an association between lower bone mineral density (BMD) and increased cardiac workload in older adults, and if this association was independent of abdominal aortic calcification (AAC). METHODS: Three hundred thirty-seven participants [mean ± SD age = 70 ± 5 years and BMI = 28 ± 5 kg/m2, 61% females] had BMD determined by dual-energy X-ray absorptiometry and AAC determined by radiography. Aortic calcification score (ACS) was determined visually in the L1-L4 vertebrae (range 0-24). Systolic blood pressure (BP) and heart rate (HR) were measured. The rate pressure product (RPP), a measure of cardiac workload, was determined by multiplying BP and HR. RESULTS: AAC was present in 205 (61%) participants. Mean ± SD RPP was 9120 ± 1823; range was 5424-18,537. In all participants, ACS was positively associated with log-transformed RPP [LnRPP] (ß = 0.011, p < 0.001), and severe calcification was positively associated with LnRPP (ß = 0.083, p = 0.004 relative to no calcification). In sex-stratified analyses, these associations were significant only in females. Lower odds of any AAC were observed per 1 g/cm2 increment in femoral neck BMD (OR = 0.08, 95% CI 0.01-0.95). A similar trend was evident in women separately (OR = 0.05, 95% CI 0-1.17) but not men. In all participants, femoral neck (ß = -0.20, p = 0.04) and total hip BMD (ß = -0.17, p = 0.04) were inversely associated with LnRPP after multivariate adjustment. Adjusting additionally for AAC reduced the strength of the association in femoral neck (ß = -0.19, p = 0.05) but not total hip BMD (ß = -0.17, p = 0.04). CONCLUSION: Lower BMD was marginally, but significantly with increased LnRPP, and this relationship was partially mediated by AAC suggesting that older adults, particularly females, with osteoporosis may have an increased cardiovascular risk.

Total and beverage-specific alcohol intake and the risk of aggressive prostate cancer: a case-control study.

BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its association with aggressive prostate cancer (APC) is uncertain. Recent studies have shown a modest increase in risk of APC associated with heavy alcohol intake while association for beverage types remain inconsistent. METHODS: Using a case-control design and self-administered questionnaire, we examined the association between APC (high grade and/or advanced stage) and frequency and quantity of alcohol intake 2 years prior to enrolment. Furthermore, we delineated the relationships for beverage-specific intakes of beer, red wine, white wine and spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake frequency of ⩾5 days per week was associated with increased risk compared with no beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine was protective at all frequencies of consumption compared with those with no wine intake. For every 10 g per week ethanol intake from beer increase, the odds of advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was observed for red or white wine while a marginal dose-response relationship was found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and possibly spirits consumption is associated with increased risk while no dose-response relationship was found for red or white wine. Wine drinkers at all frequencies have a decreased risk of APC compared with those who did not drink wine.

Dietary Quality Is Associated with Abdominal Aortic Calcification: A Mean of 18-Year Longitudinal Study in Community-Dwelling Older Adults.

OBJECTIVE: This study aimed to examine the association between baseline and changes in dietary quality assessed by the Alternative Healthy Eating Index-2010 (AHEI-2010) and abdominal aortic calcification (AAC) among community-dwelling older adults. DESIGN: Population-based longitudinal study. SETTING: A subset of the Melbourne Collaborative Cohort Study (MCCS). PARTICIPANTS: 262 community-dwelling adults (60% female) aged 53 ± 5 years at baseline. MEASUREMENTS: Dietary intake was assessed using validated Food Frequency Questionnaires at baseline (1990-1994) and follow-up (2010-2011). AAC was evaluated by radiography and dual-energy x-ray absorptiometry (DXA) at follow-up. RESULTS: Higher baseline AHEI-2010 score was associated with lower AAC severity by radiography [OR (95% CI) for Tertile 3 VS Tertile 1: 0.53 (0.29-0.99)] after adjustment for gender, age, physical activity, smoking, BMI, systolic blood pressure, plasma total cholesterol, calcium and energy intake. The association between AHEI-2010 and AAC severity by DXA was also significant in the multivariate-adjusted model [OR (95% CI) for Tertile 3 VS Tertile 1: 0.38 (0.20-0.70)]. Changes in AHEI-2010 over 18 years were not associated with AAC severity. CONCLUSION: Baseline but not the changes in AHEI-2010 was inversely associated with the risk of AAC severity suggesting that a high quality diet might help prevent or delay the progression of AAC in community-dwelling older adults and the benefits might be manifested over the long-term.

Dietary inflammatory index, Mediterranean diet score, and lung cancer: a prospective study.

PURPOSE: To investigate prospectively the associations of Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) with lung cancer. METHODS: We used data from men and women aged 40-69 years at recruitment in 1990-1994, who were participants in the Melbourne Collaborative Cohort Study (n = 35,303). A total of 403 incident lung cancer cases were identified over an average 18-year follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors, with age as the time metric. RESULTS: An inverse correlation was observed between the DII and MDS (ρ = -0.45), consistent with a higher DII being pro-inflammatory and less 'healthy,' while a high MDS reflects a 'healthier' diet. The DII was positively associated with risk of lung cancer in current smokers [HRQ4 vs Q1 = 1.70 (1.02, 2.82); Ptrend = 0.008] (p interaction between DII quartiles and smoking status = 0.03). The MDS was inversely associated with lung cancer risk overall [HR7-9 vs 0-3 = 0.64 (0.45, 0.90); Ptrend = 0.005] and for current smokers (HR7-9 vs 0-3 = 0.38 (0.19, 0.75); Ptrend = 0.005) (p interaction between MDS categories and smoking status = 0.31). CONCLUSIONS: The MDS showed an inverse association with lung cancer risk, especially for current smokers. A high DII, indicating a more pro-inflammatory diet, was associated with risk of lung cancer only for current smokers. A healthy diet may reduce the risk of lung cancer, especially in smokers.

The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer.

BACKGROUND: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. METHODS: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. RESULTS: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. CONCLUSIONS: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.

Dietary patterns as predictors of successful ageing.

OBJECTIVES: To examine associations between dietary patterns identified by factor analysis, and successful ageing. DESIGN: Prospective cohort study with diet measured in 1990-4, and successful ageing in 2003-7. Ordered logistic regression with outcome determined as dead/usual ageing/successful ageing was used to examine associations with quintile groups of dietary factor scores. PARTICIPANTS: Men and women (n=6308), without history of major illness at baseline, and aged >70 years at follow-up, or who had died before follow-up but would have been aged >70 at the commencement of follow-up, from the Melbourne Collaborative Cohort Study. MEASUREMENTS: Frequencies of intake of 121 foods at baseline were collected in a food frequency questionnaire. Anthropometry and other health and lifestyle data were collected. At follow-up, questionnaire data relating to mental health, physical function and medical history were used to define successful ageing. RESULTS: Four dietary factors were identified, characterized by higher loadings for (1) vegetables; (2) fruit, (3) feta, legumes, salad, olive oil, and inverse loadings for tea, margarine, cake, sweet biscuits and puddings; (4) meat, white bread, savoury pastry dishes and fried foods. In models excluding body size, the second factor 'Fruit' was positively associated with successful ageing (OR in top 20% vs lowest 20% of score 1.31, 95%CI (1.05-1.63), p trend across quintile groups 0.001); while the fourth factor 'Meat/fatty foods' was inversely associated (OR in top 20% vs lowest 20% of score 0.69, 95%CI (0.55-0.86), p trend across quintile groups 0.001). Factors 1 and 3 did not show significant associations with successful ageing. The association for 'Fruit' was little altered after adjustment for body size, while for 'Meat/fatty foods' the association was somewhat attenuated. CONCLUSION: A dietary pattern including plenty of fruit while limiting meat and fried foods may improve the likelihood of ageing successfully.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Second to fourth digit ratio (2D:4D), breast cancer risk factors, and breast cancer risk: a prospective cohort study.

BACKGROUND: We aimed to assess whether 2D:4D measures are associated with breast cancer risk. METHODS: We derived the ratio of the lengths of the index and ring fingers (2D:4D), and right minus left 2D:4D (Δ(r-l)) from digit lengths measured from photocopies of participants' hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. Of the 9044 women with available data, we identified 573 incident breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D:4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D:4D measures and age at menarche and menopause. RESULTS: We found a direct association between left 2D:4D and breast cancer risk, an inverse association between Δ(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk. Among breast cancer cases, both right 2D:4D and Δ(r-l) were inversely associated with age at diagnosis. We also observed associations between both right 2D:4D and Δ(r-l) and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause. CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer.

Dietary intake of B vitamins and methionine and risk of lung cancer.

BACKGROUND/OBJECTIVES: B vitamins and related enzymes involved in one-carbon metabolism are necessary for DNA replication, DNA repair and regulation of gene expression. Disruption of one-carbon mechanism may affect cancer risk. We investigated prospectively the relationship between dietary intakes of methionine, B vitamins associated with one-carbon metabolism and risk of lung cancer. SUBJECTS/METHODS: The Melbourne Collaborative Cohort Study recruited 41,514 men and women aged 40-69 years between 1990 and 1994. During follow-up of 14,595 men and 22,451 women for an average of 15 years, we ascertained 348 incident lung cancers. Dietary intake of B vitamins and methionine was estimated from a 121-item food frequency questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS: In current smokers, dietary intake of riboflavin was inversely associated with lung cancer risk (HR=0.53; 95% CI: 0.29-0.94, fifth versus first quintile; P-linear trend=0.01). No associations were found for former or never smokers or for dietary intake of any of the other B vitamins or methionine. CONCLUSION: Overall, we found little evidence of an association between B vitamins or methionine and lung cancer risk. The weak inverse association between riboflavin and lung cancer risk in current smokers needs further investigation.

Second to fourth digit ratio (2D:4D) and prostate cancer risk in the Melbourne Collaborative Cohort Study.

BACKGROUND: The ratio of the lengths of index and ring fingers (2D:4D) is a marker of prenatal exposure to sex hormones, with low 2D:4D being indicative of high prenatal androgen action. Recent studies have reported a strong association between 2D:4D and risk of prostate cancer. METHODS: A total of 6258 men participating in the Melbourne Collaborative Cohort Study had 2D:4D assessed. Of these men, we identified 686 incident prostate cancer cases. Hazard ratios (HRs) and confidence intervals (CIs) were estimated for a standard deviation increase in 2D:4D. RESULTS: No association was observed between 2D:4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92-1.08 for right, 0.93-1.08 for left). We observed a weak inverse association between 2D:4D and risk of prostate cancer for age <60, however 95% CIs included unity for all observed ages. CONCLUSION: Our results are not consistent with an association between 2D:4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D:4D and early onset prostate cancer risk.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.