Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival.

OBJECTIVE: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis. METHODS: This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 µg 1.30 and 1.43, respectively) and smokers (HRs per 100 µg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 µg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98). CONCLUSIONS: Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.

Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer.

OBJECTIVES: Limited experimental evidence suggests that omega-3 polyunsaturated (n-3) fatty acids inhibit the proliferation of ovarian cancer cells in vitro, whereas omega-6 polyunsaturated (n-6) fatty acids have been shown to promote carcinogenesis, but epidemiological studies to date have been inconclusive. Our aim was to evaluate the role of polyunsaturated fatty acids in ovarian carcinogenesis. METHODS: Participants in the Australian Ovarian Cancer Study (1,366 cases and 1,414 population controls) self-completed risk factor and food frequency questionnaires. Logistic regression models were used to calculate adjusted odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: We found no association between intake of total n-3 fatty acids from foods, or the individual n-3 fatty acids-alpha-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic acids-and ovarian cancer risk. High intake of total n-6 fatty acids was inversely associated with risk (OR for highest vs. lowest category 0.78, 95 % CI 0.60-1.00, p-trend 0.04); however, the association was restricted to n-6 fatty acids from avocado, vegetables, and nuts. Neither higher intake of the individual n-6 fatty acids nor the ratio of n-3 to n-6 fatty acids was associated with ovarian cancer risk. We found no evidence that risk varied by supplement use. CONCLUSIONS: Our data provide no evidence of a protective role for n-3 fatty acids in ovarian carcinogenesis. The benefit, if any, of higher intake of n-6 fatty acids is due to general properties of the food sources, rather than due to the n-6 fatty acids per se.

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer.

BACKGROUND/OBJECTIVE: Folates are essential for DNA synthesis and methylation, and thus may have a role in carcinogenesis. Limited evidence suggests folate-containing foods might protect against some cancers and may partially mitigate the increased risk of breast cancer associated with alcohol intake, but there is little information regarding ovarian cancer. Our aim was to evaluate the role of folate and related micronutrients, polymorphisms in key folate-metabolising genes and environmental factors in ovarian carcinogenesis. SUBJECTS/METHODS: Participants in the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires. DNA samples (1638 cases, 1278 controls) were genotyped for 49 tag single-nucleotide polymorphisms (SNPs) in the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) genes. Logistic regression models were used to generate adjusted odds ratios and 95% confidence intervals. RESULTS: We saw no overall association between the intake of folate, B vitamins or other methyl donors and ovarian cancer risk, although increasing folate from foods was associated with reduced risk among current smokers (P(trend)=0.03) and folic acid intake was associated with borderline significant increased risks among women who consumed ≥1 standard alcoholic drinks/day (odds ratio (OR)=1.64; 95% confidence interval (CI) 1.05-2.54, P(trend)=0.05). Two SNPs (rs7365052, rs7526063) showed borderline significant inverse associations with ovarian cancer risk; both had very low minor allele frequencies. There was little evidence for interaction between genotype and micronutrient intake or for variation between different histological subtypes of ovarian cancer. CONCLUSIONS: Our data provide little evidence to support a protective role for folate in ovarian carcinogenesis but suggest further evaluation of the joint effects of folic acid and alcohol is warranted.

Carbohydrate intake, glycemic load, glycemic index, and risk of ovarian cancer.

BACKGROUND: Our objective was to determine the relationship between dietary glycemic load (GL), glycemic index (GI), carbohydrate intake, and ovarian cancer risk in a population-based case-control study. PATIENTS AND METHODS: A self-administered questionnaire was used to collect data on demographic and lifestyle factors, and a food frequency questionnaire was used to collect dietary information from 1366 women with ovarian cancer and 1414 population controls. RESULTS: GL was positively associated with ovarian cancer. The adjusted odds ratio (OR) for the highest versus the lowest quartile of intake was 1.24 [95% confidence interval (CI) 1.00-1.55, P for trend = 0.03]. Fiber intake was inversely associated with risk. The OR comparing women in the highest fiber-intake group with those in the lowest was 0.78 (95% CI 0.62-0.98, P for trend = 0.11). We found no association between GI, carbohydrate intake, and ovarian cancer. In analyses stratified by body mass index, the risk estimates for GL, carbohydrate, and sugar were higher among overweight/obese women; however, the interaction term was only significant for sugar (P for interaction = 0.004). CONCLUSIONS: Our results suggest that diets with a high GL may increase the risk of ovarian cancer, particularly among overweight/obese women, and a high intake of fiber may provide modest protection.

Food intake and risk of basal cell carcinoma in an 11-year prospective study of Australian adults.

BACKGROUND/OBJECTIVE: Experimental studies suggest that dietary factors may influence skin cancer risk, but there have been few human studies of diet and basal cell carcinoma (BCC), the most common type of skin cancer. The objective was to prospectively investigate the association between food intake and incidence of BCC skin cancers. SUBJECTS/METHODS: At baseline in 1992, 1056 adults in a subtropical Australian community completed a validated food-frequency questionnaire from which we estimated the intake of 15 food groups, selected based on hypothesized associations in the literature. Between 1992 and 2002, incident, histologically confirmed BCCs were recorded in terms of number of persons newly affected by BCC, as well as BCC tumor counts. RESULTS: Intakes of the food groups were not associated with the incidence of persons affected by BCC. However, there was a borderline positive association between intake of eggs and incidence of BCC tumors (highest vs lowest tertile adjusted relative risk (RR) 1.5; 95% confidence interval (CI): 1.0-2.2; P for trend = 0.06). A borderline inverse association with potato intake (highest vs lowest tertile RR 0.7; 95% CI: 0.4-1.0, P for trend = 0.06) disappeared after exclusion of three subjects with more than 10 BCCs. CONCLUSION: Despite some suggestive evidence that egg and potato consumption may be associated with BCC tumor incidence, there are no plausible grounds for considering these as truly causal rather than chance associations. This study provides little evidence for a role of food intake in BCC prevention.

Dairy consumption and patterns of mortality of Australian adults.

BACKGROUND/OBJECTIVES: Dairy foods contain various nutrients that may affect health. We investigated whether intake of dairy products or related nutrients is associated with mortality due to cardiovascular disease (CVD), cancer and all causes. SUBJECTS/METHODS: We carried out a 16-year prospective study among a community-based sample of 1529 adult Australians aged 25-78 years at baseline. Habitual intakes of dairy products (total, high/low-fat dairy, milk, yoghurt and full-fat cheese), calcium and vitamin D were estimated as mean reported intake using validated food frequency questionnaires (FFQs) self-administered in 1992, 1994 and 1996. National Death Index data were used to ascertain mortality and cause of death between 1992 and 2007. Hazard ratios (HRs) were calculated using Cox regression analysis. RESULTS: During an average follow-up time of 14.4 years, 177 participants died, including 61 deaths due to CVD and 58 deaths due to cancer. There was no consistent and significant association between total dairy intake and total or cause-specific mortality. However, compared with those with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339 g/day) had reduced death due to CVD (HR: 0.31; 95% confidence interval (CI): 0.12-0.79; P for trend=0.04) after adjustment for calcium intake and other confounders. Intakes of low-fat dairy, specific dairy foods, calcium and vitamin D showed no consistent associations. CONCLUSIONS: Overall intake of dairy products was not associated with mortality. A possible beneficial association between intake of full-fat dairy and cardiovascular mortality needs further assessment and confirmation.

Cross-cultural comparison of Lp(a) profiles.

Lipoprotein(a) (Lp(a)) and apolipoprotein(a) (apo(a)) phenotypes as genetic markers for coronary heart disease (CHD) have been the focus of great interest in recent times. Included in this study were four Australian populations comprising 348 Anglo-Celtic Melburnians (157 men and 191 women), 339 Chinese Melburnians (169 men and 170 women), 402 South Asian Melburnians (216 men and 186 women) and 394 Aboriginal Australians from Western Australia (175 men and 219 women). Plasma Lp(a) concentrations were more highly skewed towards the lower range in the Chinese and Aboriginal groups than in the Anglo-Celtics and South Asians. Approximately 33% of Anglo-Celtics, 20% Aboriginals, 13% Chinese and 44% South Asians had plasma Lp(a) levels above the generally accepted risk threshold values of 300 mg/L. In Aboriginals and Chinese, the S4 apo(a) phenotype predominated while in Anglo-Celtics and South Asians, the highest frequency occurred in the S3 phenotype. In the S4 phenotype, Lp(a) values varied between the four populations but there was no significant difference in concentration between gender.