Variation in ribosomal DNA copy number is associated with lung cancer risk in a prospective cohort study.

Disruption of ribosomal DNA (rDNA) has been linked to a variety of diseases in humans, including carcinogenesis. To evaluate the associations between rDNA copy number (CN) and risk of lung cancer, we measured 5.8S and 18S rDNA CN in the peripheral blood of 229 incident lung cancer cases and 1:1 matched controls from a nested case-control study within a prospective cohort of male smokers. There was a dose-response relationship between quartiles of both 18S and 5.8S rDNA CN and risk of lung cancer (odds ratio [OR], 95% confidence interval [CI]: 18S: 1.0 [ref]; 1.2 [0.6-2.1]; 1.8 [1.0-3.4]; 2.3 [1.3-4.1; Ptrend = 0.0002; 5.8S: 1.0 [ref]; 1.6 [0.8-2.9]; 2.2 [1.1-4.2]; 2.6 [1.3-5.1]; Ptrend = 0.0001). The associations between rDNA CN and lung cancer risk were similar when excluding cases diagnosed within 5 years of follow-up, and when stratifying by heavy (>20 cigarettes per day) and light smokers (≤20 cigarettes per day). We are the first to report that rDNA CN may be associated with future risk of lung cancer. To further elucidate the relationship between rDNA and lung cancer, replication studies are needed in additional populations, particularly those that include non-smokers.

Association between the intake of α-linolenic acid and the risk of CHD.

The intake of the mainly plant-derived n-3 PUFA α-linolenic acid (ALA) has been reported to be associated with a lower risk of CHD. However, the results have been inconsistent. Therefore, the objective of the present study was to examine the association between the intake of ALA and the risk of CHD. Potential effect modification by the intake of long-chain n-3 PUFA (n-3 LCPUFA) was also investigated. Data from eight American and European prospective cohort studies including 148 675 women and 80 368 men were used. The outcome measure was incident CHD (CHD event and death). During 4-10 years of follow-up, 4493 CHD events and 1751 CHD deaths occurred. Among men, an inverse association (not significant) between the intake of ALA and the risk of CHD events and deaths was observed. For each additional gram of ALA consumed, a 15 % lower risk of CHD events (hazard ratios (HR) 0·85, 95 % CI 0·72, 1·01) and a 23 % lower risk of CHD deaths (HR 0·77, 95 % CI 0·58, 1·01) were observed. No consistent association was observed among women. No effect modification by the intake of n-3 LCPUFA was observed.

Effects of α-tocopherol and ß-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the Alpha-tocopherol, Beta-carotene Cancer Prevention Study.

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas ß-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α-tocopherol and ß-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96-1.11) among ß-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing ∼8 years postintervention. Body mass index significantly modified the effect of α-tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88-1.14) in normal-weight men, 0.87 (95% CI, 0.77-0.98) in overweight men, and 1.25 (95% CI, 1.01-1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98-1.05) for α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for ß-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas ß-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with α-tocopherol and ß-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality.

Metabolomic profile of response to supplementation with ß-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

BACKGROUND: Two chemoprevention trials found that supplementation with ß-carotene increased the risk of lung cancer and overall mortality. The biologic basis of these findings remains poorly understood. OBJECTIVE: The objective was to compare the on-study change in metabolomic profiles of men randomly assigned to receive or not receive ß-carotene supplements in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. DESIGN: The ATBC Study was a randomized, double-blind, placebo-controlled, primary cancer prevention trial; participants were Finnish male smokers assigned to 1 of 4 intervention groups: 1) α-tocopherol, 2) ß-carotene, 3) both, or 4) placebo. Fifty participants with both baseline and follow-up fasting serum samples were randomly selected from each of these groups. Metabolomic profiling was conducted by mass spectrometry. The association between change in each metabolite over time and trial assignment (ß-carotene or no ß-carotene) was estimated by linear regression. RESULTS: We measured 489 metabolites, and 17 changed significantly (P < 0.05) in response to ß-carotene supplementation. More of these 17 metabolites were of xenobiotic origin than would be expected by chance (9 of 60, or 15%; P = 0.00004). We also found a suggestive association with 1,5-anhydroglucitol-a marker of glycemic control (ß = -0.379, P = 0.0071). CONCLUSIONS: Male smokers supplemented with ß-carotene developed metabolomic profiles consistent with the induction of cytochrome P450 enzymes, the primary metabolizers of xenobiotics in humans. These findings may shed light on the increased mortality associated with ß-carotene supplementation in the ATBC Study and suggest the need to explore potential interactions between medication use and dietary supplements, particularly among smokers. This trial was registered at clinicaltrials.gov as NCT00342992.

Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis.

There are no observational studies or controlled trials of amyotrophic lateral sclerosis (ALS) and circulating α-tocopherol (vitamin E) for prevention of ALS. This study addresses that gap. The study population comprised 29,127 Finnish male smokers, aged 50-69 years, who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which is both a prospective cohort and a randomized, double-blind, placebo-controlled trial of α-tocopherol (50 mg/day) and ß-carotene (20 mg/day). Serum α-tocopherol and ß-carotene was assayed at baseline (1985 - 1988). Follow-up (median 16.7 years) continued through 2004. ALS cases were identified through the national Hospital Discharge Register with diagnostic verification by hospital records and death certificates. During 407,260 person-years of follow-up, 50 men were identified with ALS. For males with serum α-tocopherol concentration above the median (≥ 11.6 mg/l), the age-adjusted relative risk (RR) compared to α-tocopherol below the median, was 0.56 (95% confidence interval 0.32 - 0.99), p = 0.046. The RR among α-tocopherol supplement recipients was 0.75 (95% CI 0.32 - 1.79), p = 0.52. Neither serum ß-carotene level nor ß-carotene supplementation was associated with ALS. In conclusion, the results are consistent with a hypothesized protective effect of α-tocopherol on ALS risk. However, pooled analyses of cohorts with serum and controlled trials are needed to clarify the role of α-tocopherol in ALS risk.

Black tea consumption and risk of stroke in women and men.

PURPOSE: Our aim was examine the association between black tea consumption and risk of total stroke and stroke types in a prospective study. METHODS: A total of 74,961 Swedish women and men who were free of cardiovascular disease and cancer at baseline in 1997 were followed up through December 2008. Tea consumption was assessed with a questionnaire at baseline. Stroke cases were ascertained from the Swedish Hospital Discharge Registry. RESULTS: During a mean follow-up of 10.2 years, we ascertained 4089 cases of first stroke, including 3159 cerebral infarctions, 435 intracerebral hemorrhages, 148 subarachnoid hemorrhages, and 347 unspecified strokes. After adjustment for other risk factors, high tea consumption was associated with a significantly lower risk of total stroke; however, there was no dose-response relation (P for trend = .36). Compared with no tea consumption, the multivariable relative risk for four or more cups per day (median, 5) was 0.79 (95% confidence interval [CI], 0.62-0.998). The corresponding relative risks were 0.80 (95% CI, 0.61-1.04) for cerebral infarction and 0.68 (95% CI, 0.35-1.30) for hemorrhagic stroke. CONCLUSIONS: These findings suggest that daily consumption of four or more cups of black tea is inversely associated with risk of stroke.

Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer.

BACKGROUND: Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. METHODS: Within the ATBC Study, a randomized controlled trial of α-tocopherol and ß-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status. RESULTS: Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9). CONCLUSIONS: In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.

Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.

Dietary fats and dietary cholesterol and risk of stroke in women.

BACKGROUND: Whether intakes of dietary fat and cholesterol are associated with risk of stroke remain unclear. We examined the associations between intakes of total fat, specific types of fat, and cholesterol and risk of stroke in a prospective cohort of women. METHODS: The study population consisted of 34,670 women, aged 49-83 years, in the Swedish Mammography Cohort who were free of cardiovascular disease and completed a food-frequency questionnaire in 1997. Cox proportional hazard regression models were used to estimate relative risks (RR) with 95% confidence intervals (CI). RESULTS: During a mean follow-up of 10.4 years, we ascertained 1680 stroke events, including 1310 cerebral infarctions, 233 hemorrhagic strokes, and 137 unspecified strokes. After adjustment for other stroke risk factors, intake of long-chain omega-3 polyunsaturated fatty acids (PUFA) was inversely associated with risk of total stroke. The multivariable RR of total stroke for the highest compared with the lowest quintile of long-chain omega-3 PUFA intake was 0.84 (95% CI, 0.72-0.99; P for trend=0.04). Dietary cholesterol was positively associated with risk of total stroke (highest versus lowest quintile: RR=1.20; 95% CI, 1.00-1.44; P for trend=0.01) and cerebral infarction (corresponding RR=1.29; 95% CI, 1.05-1.58; P for trend=0.004). Total fat, saturated fat, monounsaturated fat, polyunsaturated fat, α-linolenic acid, and omega-6 PUFA intakes were not associated with stroke. CONCLUSIONS: These findings suggest that intake of long-chain omega-3 PUFAs is inversely associated with risk of stroke, whereas dietary cholesterol is positively associated with risk.

Coffee does not modify postprandial glycaemic and insulinaemic responses induced by carbohydrates.

BACKGROUND: Strong epidemiological evidence suggests that coffee consumption is associated with lower risk of type 2 diabetes. In postprandial studies, however, caffeine consumption has been associated with impaired glucose regulation. AIM OF THE STUDY: To study the acute effects of coffee and caffeine-containing soft drinks on glycaemic and insulinaemic responses. DESIGN: Twelve healthy volunteers were served each test food once and the reference glucose solution twice, containing 50 g of available carbohydrates, after an overnight fast at 1-week intervals in a random order. Capillary blood samples were drawn at 15-30 min intervals for 2 h after each study meal. The incremental areas under the curve (IAUC), glycaemic index (GI) and insulinaemic index (II), were calculated to estimate the glycaemic and insulinaemic responses. RESULTS: Glucose and insulin responses of coffees with glucose containing 150 or 300 mg of caffeine did not differ from responses of pure glucose solution; the GIs were 104 and 103, and the IIs were 89 and 92, respectively. When a bun or sucrose and milk were consumed together with coffee, lower GI values and insulin responses were observed, reflecting the carbohydrate quality and protein content of the accompaniments. Sucrose-sweetened cola produced a high GI value of 90 and an II of 61. CONCLUSIONS: Coffee does not modify glycaemic and insulinaemic responses when ingested with a carbohydrate source. Therefore, there is no need to avoid coffee as a choice of beverage in GI testing.

Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies.

BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.

Supplementation with alpha-tocopherol or beta-carotene reduces serum concentrations of vascular endothelial growth factor-D, but Not -A or -C, in male smokers.

Evidence from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study suggests that vitamin E and ß-carotene supplement use may influence the risk of several cancers. Vascular endothelial growth factors (VEGF) are proteins involved in angiogenesis, an important requirement for tumor growth and metastasis. Thus, vitamin E and ß-carotene may influence cancer risk through one or more VEGF. The ATBC Study was a randomized, double-blind, placebo-controlled, primary cancer prevention trial in which participants were assigned to 1 of 4 supplementation groups based on a 2 × 2 factorial design: 1) α-tocopherol (vitamin E); 2) ß-carotene; 3) both; or 4) placebo. For the present study, 100 cancer-free participants with follow-up serum available were randomly selected from each intervention group. VEGF-A, -C, and -D concentrations were measured by ELISA in serum obtained at baseline and after at least 2 y of supplementation. Differences in change in VEGF levels from baseline to follow-up between intervention groups were assessed using the ANOVA test. Change in VEGF-A and VEGF-C concentrations between baseline and follow-up did not differ by intervention group (P = 0.45 and 0.29, respectively). The decrease in the serum VEGF-D concentration was greater in the men supplemented with α-tocopherol (-9.7 ± 2.5%) or ß-carotene (-8.5 ± 2.7%) and tended to be greater in those supplemented with both (-6.8 ± 2.4%) compared to the placebo group, in which there was no change (-0.4 ± 3.0%) (P = 0.03). In this population of male smokers, supplementation with α-tocopherol or ß-carotene was associated with a decrease in VEGF-D levels over time. Although the mechanism through which these supplements affect cancer etiolog remains unclear, our results support the hypothesis that vitamin E and ß-carotene may influence cancer progression through VEGF-mediated lymphangiogenesis.

Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case-control study.

BACKGROUND: Vitamin D compounds inhibit prostate tumorigenesis experimentally, but epidemiologic data are inconsistent with respect to prostate cancer risk, with some studies suggesting nonsignificant positive associations. METHODS: The 25-hydroxy vitamin D [25(OH)D]-prostate cancer relation was examined in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of 50- to 69-year-old Finnish men. We matched 1,000 controls to 1,000 cases diagnosed during up to 20 years of follow-up on the basis of age (±1 year) and fasting blood collection date (±30 days). Conditional multivariate logistic regression models estimated ORs and 95% CIs. All statistical significance testing was 2-sided. RESULTS: Cases had nonsignificantly 3% higher serum 25(OH)D levels (P = 0.19). ORs (95% CIs) for increasing season-specific quintiles of 25(OH)D concentrations were 1.00 (reference), 1.29 (0.95-1.74), 1.34 (1.00-1.80), 1.26 (0.93-1.72), and 1.56 (1.15-2.12), with P(trend) = 0.01. Analyses based on prespecified clinical categories and season-adjusted values yielded similar results. These findings seemed stronger for aggressive disease [OR (95% CI) for fifth quintile of serum 25(OH)D [1.70 (1.05-2.76), P(trend) = 0.02], among men with greater physical activity [1.85 (1.26-2.72), P(trend) = 0.002], higher concentrations of serum total cholesterol [2.09 (1.36-3.21), P(trend) = 0.003] or α-tocopherol [2.00 (1.30-3.07), P(trend) = 0.01] and higher intakes of total calcium [1.82 (1.20-2.76), P(trend) = 0.01] or vitamin D [1.69 (1.04-2.75), P(trend) = 0.08], or among those who had received the trial α-tocopherol supplements [1.74 (1.15-2.64), P(trend) = 0.006]. CONCLUSION: Our findings indicate that men with higher vitamin D blood levels are at increased risk of developing prostate cancer. IMPACT: Greater caution is warranted with respect to recommendations for high-dose vitamin D supplementation and higher population target blood levels.

Coffee consumption and risk of stroke in women.

BACKGROUND AND PURPOSE: Coffee consumption has been inconsistently associated with stroke incidence and mortality in previous studies. We investigated the association between coffee consumption and stroke incidence in the Swedish Mammography Cohort. METHODS: We prospectively followed of 34,670 women without a history of cardiovascular disease or cancer at baseline in 1997. Coffee consumption was assessed in 1997 using a self-administered questionnaire. Incident stroke cases were ascertained from the Swedish Hospital Discharge Registry. RESULTS: During a mean follow-up of 10.4 years, we ascertained 1680 stroke events, including 1310 cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages, and 137 unspecified strokes. After adjustment for other risk factors, coffee consumption was associated with a statistically significant lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage but not intracerebral hemorrhage. The multivariable relative risks of total stroke across categories of coffee consumption (<1 cup/day, 1 to 2 cups/day, 3 to 4 cups/day, and ≥5 cups/day) were 1.00, 0.78 (95% CI, 0.66 to 0.91), 0.75 (95% CI, 0.64 to 0.88), and 0.77 (95% CI, 0.63 to 0.92, respectively; P for trend=0.02). The association between coffee consumption and cerebral infarction was not modified by smoking status, body mass index, history of diabetes or hypertension, or alcohol consumption. CONCLUSIONS: These findings suggest that low or no coffee consumption is associated with an increased risk of stroke in women.

Protein and fat modify the glycaemic and insulinaemic responses to a mashed potato-based meal.

Potatoes, especially mashed potatoes, are known to result in high glycaemic and insulinaemic responses. However, in most meals, potatoes are accompanied by other foods. The objective of the present study was to investigate how glycaemic and insulinaemic responses to a mashed potato meal changed when a high-fat food (rapeseed oil), a high-protein food (chicken breast) and/or salad were added to the meal. Healthy subjects (n 11) ingested the test meals once and the reference food (glucose solution) twice in a random order at 1-week intervals. Capillary blood samples were then drawn for 2 h, and glucose and insulin were analysed. The 2 h glycaemic responses to six mashed potato-containing meals varied more than twofold. The glycaemic index (GI) of pure mashed potato was 108, whereas combined with chicken breast, rapeseed oil and salad, it was only 54. The latter GI also differed considerably from its predicted value of 103, which was based on the individual GI of the components of the meal. The insulinaemic indices of the mashed potato-based meals varied between 94 and 148. Chicken breast in the meal increased the insulinaemic response, and rapeseed oil diminished it. However, the insulinaemic response to mashed potato with chicken breast and rapeseed oil was lower than that to mashed potato alone. In conclusion, the protein, fat and salad contents of a meal exert considerable influence on the glycaemic and insulinaemic responses to mashed potatoes. Furthermore, the estimation of the GI of a mixed meal by calculation is imprecise.

Serum vitamin D and risk of bladder cancer.

Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and ß-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e., <25, 25 to <37.5, 37.5 to <50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L; <25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to <37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to <50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend=0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend=0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women.

Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies.

OBJECTIVE: To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer. METHODS: Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model. RESULTS: Among 676,141 men and women, 5,454 colon cancer cases were identified (7-20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76-1.02, >4,000 vs. ≤ 1,000 µg/day) for vitamin A, 0.81 (0.71-0.92, >600 vs. ≤ 100 mg/day) for vitamin C, and 0.78 (0.66-0.92, > 200 vs. ≤ 6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81-0.96). CONCLUSIONS: Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Risk of colon cancer and coffee, tea, and sugar-sweetened soft drink intake: pooled analysis of prospective cohort studies.

BACKGROUND: The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. METHODS: We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. RESULTS: Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P(trend) = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P(trend) = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P(trend) = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). CONCLUSIONS: Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.