The age-dependent association of risk factors with pancreatic cancer.

BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.

Height as a mediator of sex differences in cancer risk.

BACKGROUND: Globally, age-standardized incidence rates for most cancers at shared sites are substantially and consistently higher in men than in women. Differences in established risk factors are unable to account for much of the sex disparity. We hypothesized that variability in height may be important in explaining sex differences in cancer risk. PATIENTS AND METHODS: We included 49 372 men from the Health Professionals Follow-up Study (1986-2014) and 115 612 women from the Nurses' Health Study (1980-2014). Height was reported at baseline and biennial questionnaires were used to collect information on cancer risk factors. We examined the association between sex and cancer incidence at shared anatomic sites using Cox proportional hazards models and performed mediation analysis to determine the percent of the association that was accounted for by height. RESULTS: Over up to 34 years of follow-up, 21 307 incident cases of cancers at shared sites (7705 men, 13 602 women) were documented. After adjusting for major cancer risk factors, men had a 39% increased risk of shared cancers overall (hazard ratio = 1.39; 95% confidence interval = 1.33-1.45) of which 35% (95% confidence interval = 24-46) was mediated by height. The excess risk of cancer for men was also partially explained by height for several specific cancers (gastrointestinal, melanoma, kidney, brain, hematologic). Mediation by height tended to be stronger among never smokers or those who adhered to a healthy lifestyle, and for cancers with fewer known environmental risk factors. CONCLUSIONS: Differences in height among men and women partially mediated the association between sex and cancer incidence at several shared sites. Hence, mechanisms underlying the relationship between height and cancer may be important determinants of sex disparities in cancer incidence.

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance).

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.

Male pattern baldness and risk of colorectal neoplasia.

BACKGROUND: Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. METHODS: From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. RESULTS: Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). CONCLUSIONS: Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.

Television watching and risk of colorectal adenoma.

BACKGROUND: Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis. METHODS: We conducted a cross-sectional analysis among 31 065 men with ⩾1 endoscopy in the Health Professionals Follow-up Study (1988-2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n=4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0-6, 7-13, 14-20, and 21+ h per week) were 1.00 (referent), 1.09 (1.01-1.17), 1.16 (1.06-1.27), and 1.10 (0.97-1.25) (OR per 14-h per week increment=1.11; 95% CI: 1.04-1.18; Ptrend=0.001). Compared with the least sedentary (0-6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14+ h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05-1.49), particularly for high-risk adenoma. CONCLUSIONS: Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity.

Visceral adiposity and colorectal adenomas: dose-response meta-analysis of observational studies.

BACKGROUND: Obesity-related hormonal and metabolic perturbations implicated in colorectal carcinogenesis are mainly driven by visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT). Yet, most epidemiologic studies have examined the relationship between excess adiposity and colorectal neoplasia using body mass index (BMI) and waist circumference (WC). Due to the inability of BMI and WC to distinguish VAT from SAT, they are likely to have underestimated the true association. PATIENTS AND METHODS: We conducted a dose-response meta-analysis to summarize the relationships between VAT and colorectal adenomas and to examine the value of VAT as an independent risk factor beyond BMI, WC, and SAT. PubMed and Embase were searched through September 2014 to identify relevant observational studies. The summary odds ratio (OR) 95% confidence interval (CI) were estimated using a random-effects model. RESULTS: In linear dose-response meta-analysis, the summary OR for each 25 cm(2) increase in VAT area was 1.13 (95% CI 1.05-1.21; I(2) = 62%; 6 studies; 2776 cases; range of VAT area = 30-228 cm(2)). The dose-response curve suggested no evidence of nonlinearity (Pnon-linearity = 0.37). In meta-analysis comparing the highest versus lowest category of VAT based on 12 studies, a positive association between VAT and adenomas remained statistically significant even after adjustment for BMI, WC, and SAT. In contrast, adjustment for VAT substantially attenuated associations of BMI, WC, and SAT with adenomas. Across the studies, VAT was more strongly associated with advanced adenomas than nonadvanced adenomas. CONCLUSIONS: VAT may be the underlying mediator of the observed associations of BMI and WC with adenomas, increasing adenoma risk continuously over a wide range of VAT area. Considering that the joint use of BMI and WC better captures VAT than the use of either one, clinicians are recommended to use both BMI and WC to identify those at high risk for colorectal neoplasia.

Personal history of gallstones and risk of incident psoriasis and psoriatic arthritis in U.S. women.

BACKGROUND: Metabolic syndrome has been associated with both gallstones and psoriasis, suggesting a potential biological linkage between gallstones and psoriasis. However, the association between gallstones and psoriasis has not yet been studied. OBJECTIVES: To investigate the association between gallstones and psoriasis. METHODS: This was a prospective cohort study [Nurses' Health Study II (1991-2005)]. Women aged 25-42 years who were free from psoriasis at baseline and who responded to a 2005 follow-up questionnaire regarding their diagnosis of psoriasis were included (n = 89,230). The relative risk (RR) of developing psoriasis or psoriatic arthritis (PsA), which were self-reported and validated by supplemental questionnaires, was measured. RESULTS: In this population, 2206 participants had gallstones confirmed by a history of cholecystectomy at baseline. A total of 642 individuals had a diagnosis of incident psoriasis, of whom 157 had concomitant PsA. After adjusting for known risk factors of psoriasis besides body mass index (BMI), a baseline history of cholecystectomy-confirmed gallstones was associated with increased risk of psoriasis [multivariate-adjusted RR 2·20, 95% confidence interval (CI) 1·56-3·10] and concomitant PsA (multivariate-adjusted RR 4·41, 95% CI 2·70-7·18). After additionally adjusting for BMI, the fully adjusted RRs associated with a history of cholecystectomy-confirmed gallstones were 1·70 (95% CI 1·20-2·41) for psoriasis and 2·96 (95% CI 1·80-4·89) for PsA. CONCLUSIONS: Personal history of gallstones was associated with an increased risk of psoriasis and PsA, independent of obesity, in a cohort of U.S. women.

Egg intake and cancers of the breast, ovary and prostate: a dose-response meta-analysis of prospective observational studies.

Evidence suggests that egg intake may be implicated in the aetiology of sex hormone-related cancers. However, dose-response relationships between egg intake and such cancers are unclear. Thus, we conducted a dose-response meta-analysis to summarise the dose-response relationships between egg consumption and the risk of breast, prostate and gynaecological cancers. A literature search was performed using PubMed and Embase up to April 2015 to identify relevant prospective observational studies. Summary relative risk (RR) and 95% CI were estimated using a random-effects model. For breast cancer, the linear dose-response meta-analysis found a non-significantly increased risk (RR for an increase of 5 eggs consumed/week: 1·05, 95% CI 0·99, 1·11, n 16,023 cases). Evidence for non-linearity was not statistically significant (P non-linearity= 0·50, n 15,415 cases) but consuming ≥ 5 eggs/week was significantly associated with an increased risk of breast cancer compared with no egg consumption, with the summary RR being 1·04 (95% CI 1·01, 1·07) for consuming 5 eggs/week and 1·09 (95% CI 1·03, 1·15) for consuming about 9 eggs/week. For other cancers investigated, the summary RR for an increase of 5 eggs consumed/week was 1·09 (95% CI 0·96, 1·24, n 2636 cases) for ovarian cancer; 1·47 (95% CI 1·01, 2·14, n 609 cases) for fatal prostate cancer, with evidence of small-study effects (P Egger= 0·04). No evidence was found for an association with the risk of total prostate cancer. While our conclusion was tempered by the potential for publication bias and confounding, high egg intake may be associated with a modestly elevated risk of breast cancer, and a positive association between egg intake and ovarian and fatal prostate cancers cannot be ruled out.

Long-term use of multivitamins and risk of colorectal adenoma in women.

BACKGROUND: Use of multivitamins may reduce the risk of colorectal adenoma, but the duration of use needed is unclear. METHODS: We prospectively examined years of multivitamin use and risk of colorectal adenoma among 43,641 women who had a first endoscopy between 1991 and 2007 in the Nurses' Health Study II. Use of multivitamins was assessed through biennial questionnaires since 1989. RESULTS: We documented 2277 colorectal adenoma cases. Reporting multivitamin use at any time during the study period compared with never reporting its use was associated with a reduced risk of adenoma (multivariable relative risk (RR)=0.86, 95% confidence interval (CI): 0.76-0.97). There was no clear trend with duration of multivitamin use: years of use compared with never use, ≤ 4 years (RR=0.84, 95% CI: 0.74-0.96), 5-9 years (RR=0.89, 95% CI: 0.77, 1.02), 10-14 years (RR=0.86, 95% CI: 0.74, 1.01), 15-19 years (RR=0.85, 95% CI: 0.70, 1.02), and 20-26 years (RR=0.80, 95% CI: 0.64, 1.01); (P trend=0.87). The strongest associations (years of use vs never user) were for size of adenoma: large (≥ 1 cm) <4 years (RR=0.75, 95% CI: 0.58-0.96) and in alcohol users (≥ 1.4 g per day) 20-26 years (RR=0.67, 95% CI: 0.49-0.91). CONCLUSION: Our findings suggest that use of multivitamins is associated with lower risk of colorectal adenoma, even with relatively short duration of use.

A prospective study of plasma inflammatory markers and risk of colorectal cancer in men.

BACKGROUND: Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent. METHODS: We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumour necrosis factor receptor 2 (sTNFR-2) with incident CRC among 274 cases and 532 matched controls nested in the Health Professionals Follow-up Study. RESULTS: Multivariate relative risk (RR) of CRC comparing the extreme quartiles of plasma IL-6 was 1.54 (95% confidence interval (CI), 0.99-2.40; P(trend)=0.02). However, after excluding cases diagnosed within 2 years of blood draw, this association was not statistically significant (RR=1.26, 95% CI, 0.78-2.05; P(trend)=0.21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (P(interaction)=0.03). We did not observe any significant association between CRP or sTNFR-2 and CRC. CONCLUSION: Plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation.

Nut consumption and risk of pancreatic cancer in women.

BACKGROUND: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. METHODS: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ≥2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47-0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48-0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. CONCLUSION: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.

Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study.

BACKGROUND: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD: We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). RESULTS: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (P(trend)<0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (P(trend)=0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (P(trend)=0.002) but not in multivariate-adjusted model (P(trend)=0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. CONCLUSION: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women.

Body mass index and Barrett's oesophagus in women.

OBJECTIVE: Excess body mass is associated with symptoms of gastro-oesophageal reflux disease, and cross-sectional studies suggest an association between body mass index (BMI) and Barrett's oesophagus. The present study sought prospectively to examine the influence of BMI and other anthropomorphic measures on the risk for Barrett's oesophagus among women. METHODS: This was a prospective study of 15 861 women who participated in the Nurses' Health Study, without a history of cancer, who underwent upper gastrointestinal endoscopy for any reason between 1986 and 2004. The main outcome measures were 261 cases of pathologically confirmed specialised intestinal metaplasia within the oesophagus (Barrett's oesophagus). Self-reported data on weight were collected from biennial questionnaires. Self-reported height was collected in 1976, and self-reported waist and hip circumferences were collected in 1986. RESULTS: Compared with women with a BMI of 20-24.9 kg/m(2), women with a BMI of 25-29.9 had a multivariate OR for Barrett's oesophagus of 0.92 (95% CI 0.66 to 1.27), women with a BMI > or =30 had a multivariate OR of 1.52 (95% CI 1.02 to 2.28) and women with a BMI <20 had a multivariate OR of 0.92 (95% CI 0.65 to 1.31). Results were similar when controlling for symptoms of gastro-oesophageal reflux, and among the entire Nurses' Health Study cohort (n = 93 609) regardless of a history of endoscopy. In contrast, waist-to-hip ratio, waist circumference and height did not appear to be associated with Barrett's oesophagus. CONCLUSIONS: Obese, but not overweight, women appear to be at increased risk for Barrett's oesophagus.

Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer.

BACKGROUND: In an earlier study, a 25-hydroxyvitamin D(3) (25(OH)D) score calculated from known predictors of vitamin D status significantly predicted plasma levels of 25(OH)D and the risk of colorectal cancer, but the influence of the 25(OH)D score on survival after diagnosis is unknown. MATERIALS AND METHODS: We prospectively examined the influence of post-diagnosis predicted 25(OH)D levels on mortality among 1017 participants in the Nurses' Health Study and Health Professionals Follow-Up Study who were diagnosed with colorectal cancer from 1986 to 2004. Colorectal cancer-specific and overall mortality according to quintiles of predicted 25(OH)D levels were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors of survival. RESULTS: Higher predicted 25(OH)D levels were associated with a significant reduction in colorectal cancer-specific (P trend=0.02) and overall mortality (P trend=0.002). Compared with levels in the lowest quintile, participants with predicted 25(OH)D levels in the highest quintile had an adjusted HR of 0.50 (95% CI, 0.26-0.95) for cancer-specific mortality and 0.62 (95% CI, 0.42-0.93) for overall mortality. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of colorectal cancer may be associated with improved survival. Further study of the vitamin D pathway in colorectal cancer is warranted.

Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth.

BACKGROUND: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. METHODS: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. FINDINGS: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). INTERPRETATION: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men.

OBJECTIVE: To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group. DESIGN: Blood aliquots were pooled for each decile of intake of two carotenoids and alpha tocopherol as measured by FFQ. These pooled samples were analyzed for nutrient content, and the resultant blood levels were plotted against the median for each decile of intake. In addition, adipose tissue samples taken from each man were analyzed for content of specific fatty acids. We calculated the Spearman correlations comparing intakes of specific fatty acids as percent of total fat intake, adjusted for energy intake, as measured by FFQ, with the percentage of the corresponding fatty acid in adipose tissue. SUBJECTS AND SETTINGS: African-American men (N=104) with prostate cancer were recruited from a Detroit physician's practice and completed a detailed FFQ. RESULTS: Comparing decile 10 with decile 1 intake of nutrients as measured by FFQ, there was a 32% higher blood level of lycopene, a 288% higher blood level of beta carotene and a 100% higher blood level of alpha tocopherol. The Spearman correlation coefficients between intakes of linoleic acid, alpha linolenic acid, long-chain n-3 fatty acids and trans fatty acid measured by FFQ and the corresponding adipose tissue levels were between 0.10 and 0.47. CONCLUSION: The FFQ was able to distinguish meaningful differences in biochemical measurements of selected nutrients and presumably corresponding differences in the extremes of intake in African-American men with prostate cancer who were likely to be motivated to report accurately. However, the results found are similar to those found in other populations.

Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort.

BACKGROUND: Previous epidemiologic studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with regard to the types of fruits and vegetables consumed. We examined total fruit and vegetable intake, as well as intakes of subtypes of fruits and vegetables, in relation to bladder cancer risk in a large male prospective cohort study. METHODS: Two hundred fifty-two cases of incident bladder cancer were diagnosed from 1986 through January 31, 1996, among 47,909 men enrolled in the Health Professionals Follow-up Study. Each participant in this cohort completed a 131-item food-frequency questionnaire in 1986 and subsequently in 1990 and 1994. We used logistic regression analyses to examine fruit and vegetable intake in relation to bladder cancer risk, after adjusting for age, history of cigarette smoking, current smoking status, geographic region, total fluid intake, and caloric intake. RESULTS: We observed a weak, inverse association that was not statistically significant between total fruit and vegetable intake and bladder cancer risk. Intake of cruciferous vegetables was inversely associated with risk (relative risk = 0.49; 95% confidence interval = 0.32-0.75, for the highest category of cruciferous vegetable intake compared with the lowest), but intakes of yellow or green leafy vegetables or carotenoid-rich vegetables were not associated with risk. Individual cruciferous vegetables, except for coleslaw, were all inversely related to bladder cancer risk, but only the associations for broccoli and cabbage were statistically significant. CONCLUSIONS: Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.

Prospective study of plasma fatty acids and risk of prostate cancer.

BACKGROUND: Although some evidence suggests that dietary fat intake is related to prostate cancer, epidemiologic studies have been inconsistent. PURPOSE: Our purpose was to assess the association between plasma lipid levels, particularly linoleic and alpha-linolenic acids, and the development of prostate cancer. METHODS: In 1982, at the start of the Physicians' Health Study, 14916 U.S. male physicians provided plasma samples, which were frozen at -82 degrees C. Data accumulated from a series of questionnaires were used to assess the intake of various foods. We used a nested case-control design to compare the fatty acid compositions in plasma from 120 men who later developed prostate cancer with 120 matched controls who did not. Individual fatty acids were measured in plasma as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic regression models were used to obtain odds ratio estimates while adjusting simultaneously for the effects of one or more potential confounders. RESULTS: The relative risks (RRs) of prostate cancer for men in successively higher quartiles of plasma alpha-linolenic acid level were 3.0 (95% confidence interval [CI] = 1.2-7.3), 3.4 (95% CI = 1.6-7.5), and 2.1 (95% CI = 0.9-4.9), compared with those with levels below the detection threshold (P trend = .03). For linoleic acid, RRs in successively higher quartiles were 0.7 (95% CI = 0.4-1.5), 0.8 (95% CI = 0.4-1.6), and 0.6 (95% CI = 0.3-1.3), with the lowest quartile as referent (P trend = .24). The effect estimates were not notably altered by adjustment for exercise, body mass, meat and dairy consumption, or other fatty acid levels in the plasma. The RR for eating red meat at least five times per week compared with less than once a week was 2.5 (95% CI = 0.9-6.7) and was little changed by adjustment for alpha-linolenic acid, although alpha-linolenic acid levels were correlated with intake of red meat and butter. The association of alpha-linolenic acid levels with prostate cancer was greater among men with low linoleic acid and reduced meat intake. CONCLUSIONS: These results suggest that low plasma levels of alpha-linolenic acid might be associated with reduced risk of prostate cancer, independently of high meat intake. High linoleic acid and low marine fatty oils were not associated with increased risk, as previously hypothesized. IMPLICATIONS: The effects of dietary alpha-linolenic acid, particularly from vegetable sources, warrant further study. The effects of dietary linoleic acid and marine fatty acids seen in animal bioassays might not apply to human prostate cancer.

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.