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Objective: A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism., Methods: We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial., Results: During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively)., Conclusion: In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.

Diets high in red and processed meats are associated with carcinogenesis of the large intestine, but no prospective study has examined meat and fat intake in relation to cancer of the small intestine. We prospectively investigated meat and fat intakes, estimated from a food frequency questionnaire, in relation to small intestinal cancer among half a million men and women enrolled in the NIH-AARP Diet and Health Study. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During up to 8 years of follow-up, 60 adenocarcinomas and 80 carcinoid tumors of the small intestine were diagnosed. Despite slightly elevated HRs for red meat, there were no clear associations for red or processed meat intake and either adenocarcinoma or carcinoid tumors of the small intestine. In contrast, we noted a markedly elevated risk for carcinoid tumors of the small intestine with saturated fat intake in both the categorical (highest versus lowest tertile: HR, 3.18; 95% CI, 1.62-6.25) and continuous data (HR, 3.72; 95% CI, 1.79-7.74 for each 10-g increase in intake per 1,000 kcal). Our findings suggest that the positive associations for meat intake reported in previous case-control studies may partly be explained by saturated fat intake.

Background: Results from the Women's Health Initiative trial raise new questions regarding the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk., Methods: We analyzed data from 126,638 females, ages 50 to 71 years at baseline, who completed two questionnaires (1995--1996 and 1996--1997) as part of the NIH-AARP Diet and Health Cohort Study and in whom 3,657 incident breast cancers were identified through June 30, 2002. Hormone-associated relative risks (RR) and 95% confidence intervals (CI) of breast cancer were estimated via multivariable regression models., Results: Among thin women (body mass index < 25 kg/m2), ET use was associated with a significant 60% excess risk after 10 years of use. EPT was associated with a significantly increased risk among women with intact uteri, with the highest risk among current, long-term (> or = 10 years) users (RR, 2.44; 95% CI, 2.13-2.79). These risks were slightly higher when progestins were prescribed continuously than sequentially (< 15 days/mo; respective RRs of 2.76 versus 2.01). EPT associations were strongest in thin women, but elevated risks persisted among heavy women. EPT use was strongly related to estrogen receptor (ER)-positive tumors, requiring consideration of this variable when assessing relationships according to other clinical features. For instance, ER- ductal tumors were unaffected by EPT use, but all histologic subgroups of ER+ tumors were increased, especially low-grade and mixed ductal-lobular tumors., Conclusions: Both ET and EPT were associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors.

Objective: In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer., Methods: We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50-71 years at baseline in 1995-1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression., Results: Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68-0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70-1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61-0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65-1.00 for > or =7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67-0.99 for > or =7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14-2.27 for > or =9 h/day) among men. Similar, but less pronounced relations were observed in women., Conclusion: Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk.

Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies.

Increased fruit and vegetable consumption may protect against lung cancer, although epidemiologic findings are inconclusive. The authors prospectively examined associations between lung cancer risk and intakes of fruit, vegetables, and botanical subgroups in 472,081 participants aged 50-71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline (1995-1996) with a 124-item dietary questionnaire. A total of 6,035 incident lung cancer cases were identified between 1995 and 2003. Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women. Higher consumption of several botanical subgroups, however, was significantly inversely associated with risk, but only in men. For example, the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae, convolvulaceae, and umbelliferae were 0.82 (95% confidence interval (CI): 0.73, 0.91), 0.86 (95% CI: 0.75, 0.96), and 0.86 (95% CI: 0.78, 0.96), respectively; corresponding relative risks in women were 0.97 (95% CI: 0.85, 1.12), 0.95 (95% CI: 0.83, 1.09), and 0.92 (95% CI: 0.80, 1.06). These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men, although the findings could also be due to residual confounding by smoking or chance.

Background & Aims: Although a number of epidemiologic studies have found dietary fiber and whole grains to be inversely associated with colorectal cancer incidence, studies of dietary and other risk factors for small intestinal cancer have been sparse and all of a case-control design. We conducted a prospective cohort study to determine the relationship between intake of dietary fiber/whole grains and the incidence of small intestinal cancer., Methods: We analyzed dietary data collected in 1995 and 1996 from 293,703 men and 198,618 women in the National Institutes of Health-AARP Diet and Health Study. We used multivariate Cox proportional hazards models to estimate relative risk (RR) and 2-sided 95% confidence intervals (CIs) for quintiles of dietary fiber and whole grain intake., Results: Through 2003, 165 individuals developed small intestinal cancers. Dietary fiber/whole grain intake was generally associated with a lower risk of small intestinal cancer. The multivariate RRs (95% CIs; 5th vs 1st intake quintile) were 0.79 (0.43-1.44; P trend, .41) for total dietary fiber, 0.51 (0.29-0.89; P trend, .01) for fiber from grains, and 0.59 (0.33-1.05; P trend, .06) for whole grain foods., Conclusions: Intake of fiber from grains and whole-grain foods was inversely associated with small intestinal cancer incidence; the RR values were consistent with those from the same dietary factors for large bowel cancer in this cohort. In conjunction with the anatomic and physiologic commonalities of the large and small bowel, as well as the mutually increased risks for second cancer for both organs, grain fiber and whole grain foods seem to protect against lower gastrointestinal cancers.

Physical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995-1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15-18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; P(trend) = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; P(trend) = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67-1.20; P(trend) = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91-1.03; P(trend) = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; P(trend) = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; P(trend) = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort.

Renal cell cancer (RCC) incidence has increased in the United States over the past three decades. The authors analyzed the association between body mass index (BMI) and invasive RCC in the National Institutes of Health (NIH)-AARP Diet and Health Study, a large, prospective cohort aged 50-71 years at baseline initiated in 1995-1996, with follow-up through December 2003. Detailed analyses were conducted in a subcohort responding to a second questionnaire, including BMI at younger ages (18, 35, and 50 years); weight change across three consecutive age intervals; waist, hip, and waist-to-hip ratio; and height at age 18 years. Incident RCC was diagnosed in 1,022 men and 344 women. RCC was positively and strongly related to BMI at study baseline. Among subjects analyzed in the subcohort, RCC associations were strongest for baseline BMI and BMI recalled at age 50 years and were successively attenuated for BMI recalled at ages 35 and 18 years. Weight gain in early (18-35 years of age) and mid- (35-50 years of age) adulthood was strongly associated with RCC, whereas weight gain after midlife (age 50 years to baseline) was unrelated. Waist-to hip ratio was positively associated with RCC in women and with height at age 18 years in both men and women.

Background: Although it has been hypothesized that hyperglycemia, hyperinsulinemia, and insulin resistance are involved in the development of pancreatic cancer, results from epidemiologic studies of added sugar intake are inconclusive., Objective: Our objective was to investigate whether the consumption of total added sugar and sugar-sweetened foods and beverages is associated with pancreatic cancer risk., Design: In 1995 and 1996, we prospectively examined 487 922 men and women aged 50-71 y and free of cancer and diabetes. Total added dietary sugar intake (in tsp/d; based on the US Department of Agriculture's Pyramid Servings Database) was assessed with a food-frequency questionnaire. Relative risks (RRs) and 95% CIs were calculated with adjustment for total energy and potential confounding factors., Results: During an average 7.2 y of follow-up, 1258 incident pancreatic cancer cases were ascertained. The median intakes for the lowest and highest quintiles of total added sugar intake were 12.6 (3 tsp/d) and 96.2 (22.9 tsp/d) g/d, respectively. No overall greater risk of pancreatic cancer was observed in men or women with high intake of total added sugar or sugar-sweetened foods and beverages. For men and women combined, the multivariate RRs of the highest versus lowest intake categories were 0.85 (95% CI: 0.68, 1.06; P for trend = 0.07) for total added sugar, 1.01 (0.82,1.23; P for trend = 0.58) for sweets, 0.98 (0.82,1.18; P for trend = 0.49) for dairy desserts, 1.12 (0.91,1.39; P for trend = 0.35) for sugar added to coffee and tea, and 1.01 (0.77,1.31; P for trend = 0.76) for regular soft drinks., Conclusion: Our results do not support the hypothesis that consumption of added sugar or of sugar-sweetened foods and beverages is associated with overall risk of pancreatic cancer.

Evidence for a relation between physical activity and renal cell cancer has been inconsistent. The authors examined physical activity in relation to renal cell cancer in a large, prospective US cohort study of 482,386 participants (289,503 men and 192,883 women) aged 50-71 years at baseline (1995-1996). At baseline, participants reported their frequency of exercise of at least 20 minutes' duration, intensity of daily routine activity, and frequency of physical activity during adolescence. During 8.2 years of follow-up (through December 2003), 1,238 cases of renal cell cancer were ascertained. In multivariate Cox regression models adjusted for renal cell cancer risk factors, the authors observed that current exercise, routine physical activity, and activity during adolescence were associated with a reduced risk of renal cell cancer. The multivariate relative risks for the highest activity level as compared with the lowest were 0.77 (95% confidence interval (CI): 0.64, 0.92; p(trend) = 0.10) for current exercise, 0.84 (95% CI: 0.57, 1.22; p(trend) = 0.03) for routine physical activity, and 0.82 (95% CI: 0.68, 1.00; p(trend) = 0.05) for activity during adolescence. The authors conclude that increased physical activity, including activity during adolescence, is associated with reduced risk of renal cell cancer.

Background: Whether women are more susceptible than men to lung cancer caused by cigarette smoking has been controversial. To address this question, we aimed to compare incidence rates of lung cancer by stratum of smoking use in men and women of the National Institutes of Health (NIH)-AARP cohort., Methods: Participants in the NIH-AARP Diet and Health study responded to a postal questionnaire between Oct 13, 1995, and May 6, 1996, and were followed up until Dec 31, 2003. The questionnaire asked participants about their past and current smoking status, demographics, alcohol intake, tobacco smoking, physical activity, and included a food-frequency questionnaire of 124 items. Incident lung cancers were identified by linkage to individual state cancer registries. We present age-standardised incidence rates for cancer and multivariate hazard ratios (HRs) adjusted for potential confounders, with 95% CIs. This study conforms to the STROBE guidelines., Findings: 279 214 men and 184 623 women from eight states in the USA aged 50-71 years at study baseline were included in this analysis. During follow-up, lung cancers occurred in 4097 men and 2237 women. Incidence rates were 20.3 (95% CI 16.3-24.3) per 100 000 person-years in men who had never smoked (99 cancers) and 25.3 (21.3-29.3) in women who had never smoked (152 cancers); for this group, the adjusted HR for lung cancer was 1.3 (1.0-1.8) for women compared with men. Smoking was associated with increased risk of lung cancer in men and women. The incidence rate of current smokers who smoked more than two packs per day was 1259.2 (1035.0-1483.3) in men and 1308.9 (924.2-1693.6) in women. In current smokers, in a model adjusted for typical smoking dose, the HR was 0.9 (0.8-0.9) for women compared with men. For former smokers, in a model adjusted for years of cessation and typical smoking dose, the HR was 0.9 (0.9-1.0) for women compared with men. Incidence rates of adenocarcinoma, small-cell carcinoma, and undifferentiated tumours were similar in men and women; incidence rates of squamous tumours in men were about twice that in women., Interpretation: Our findings suggest that women are not more susceptible than men to the carcinogenic effects of cigarette smoking in the lung. In smokers, incidence rates tended to be higher in men than women with comparable smoking histories, but differences were modest; smoking was strongly associated with lung cancer risk in both men and women. Future studies should confirm whether incidence rates are indeed higher in women who have never smoked than in men who have never smoked.

Objective: Fruit and vegetable intake may protect against gastric cancer incidence. Results from case-control studies have indicated an inverse association, but results from cohort studies are inconsistent., Methods: We prospectively investigated the association in 490,802 participants of the NIH-AARP Diet and Health Study using Cox proportional hazards models adjusted for gastric cancer risk factors. We present hazard ratios (HR) and 95% confidence intervals (CI) per increase of one daily serving per 1,000 calories., Results: During 2,193,751 person years, 394 participants were diagnosed with incident gastric cancer. We observed no significant associations between total fruit and vegetable intake (1.01, 0.95-1.08), fruit intake (1.04, 0.95-1.14), or vegetable intake (0.98, 0.88-1.08) and gastric cancer risk. Results did not vary by sex or anatomic subsite (cardia versus non-cardia). All 13 botanical subgroups examined had no significant associations with either anatomic sub-site., Conclusion: We did not observe significant associations between overall fruit and vegetable intake and gastric cancer risk in this large prospective cohort study.

Squamous head and neck cancers include cancers of the oral cavity, pharynx and larynx are the sixth leading cause of cancer mortality worldwide, resulting in more than 350,000 deaths annually. Intake of fruit and vegetables may protect against head and neck cancer incidence, although few prospective studies have examined this association. We investigated this relation in 490,802 United States participants of the NIH-AARP Diet and Health cohort using Cox proportional hazard models adjusted for potential confounders. During 2,193,751 person years of follow-up from 1995/1996-2000, 787 participants were diagnosed with head and neck cancer. We found an inverse association between total fruit and vegetable intake and head and neck cancer risk (per serving/day/1,000 calories, Hazard Ratio, 95% Confidence interval: 0.94, 0.89-0.99). In models mutually adjusted for fruit and vegetable intake, the association was stronger for vegetables (fifth vs. first quintile: 0.65, 0.50-0.85) than for fruits (fifth vs. first quintile: 0.87, 0.68-1.11). When further subclassified into botanical groups, those in the highest tertile of leguminosae (dried beans, string beans and peas, 0.80, 0.67-0.96), rosaceae (apples, peach, nectarines, plums, pears and strawberries, 0.60, 0.49-0.73), solanaceae (peppers and tomatoes, 0.82, 0.69-0.98) and umbelliferae (carrots, 0.73, 0.60-0.89) had decreased risk of head and neck cancer, but no significant associations were seen for 9 other botanical groups. Results from this large prospective observational study are consistent with previous case-control studies and support the hypothesis that total fruit and vegetable intake is associated with reduced risk of head and neck cancer., ((c) 2008 Wiley-Liss, Inc.)

Biliary tract cancer, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, is a rare but highly fatal malignancy. Obesity and gallstones, both related to insulin resistance, are linked to an elevated risk of biliary cancer. The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs), expressed in adipose tissue, play a key role in the regulation of obesity-related insulin sensitivity, thus genetic variants of these two receptor genes may be related to biliary cancer and stones. We examined the associations of seven single-nucleotide polymorphisms in the PPAR-gamma, PPAR-delta, RXR-alpha, RXR-beta and INS genes with biliary cancer and stones in a population-based case-control study in Shanghai, China. We included 237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater cancer cases, 895 stone cases and 786 population controls. Relative to individuals with the RXR-beta C51T (rs2076310) CC genotype, those having the TT genotype had a 1.6-fold risk for bile duct cancer [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 0.99-2.84], with a more pronounced association among men (OR = 2.30; 95% CI = 1.14-4.65; P interaction = 0.07). This marker was also associated with a higher risk of gallstones among subjects with a higher body mass index (BMI) (>or=23 kg/m(2)) (OR = 1.80; 95% CI = 1.09-2.94), although the interaction with BMI was not statistically significant (P interaction = 0.28). No association was found between other variants and biliary cancers and stones. Results from this population-based study suggest that certain genetic variants involved in the regulation of obesity-related insulin sensitivity may increase susceptibility to bile duct cancer and gallstones.

Background: Epidemiologic studies of body mass index (BMI) in relation to mortality commonly exclude persons with health conditions and/or a history of smoking to prevent bias resulting from illness-related weight loss ('reverse causation'). Analysis of BMI from an earlier time period may minimize reverse causation without requiring exclusion of participants based on disease or smoking history., Methods: We prospectively examined BMI based on technician measurements of weight and height from 10 years prior to start of follow-up in relation to subsequent mortality in a cohort of 50 186 women who were 40-93 years old at baseline in 1987-1989. Deaths were ascertained through the US National Death Index. Proportional hazards regression was used to estimate hazard ratios (HRs) of mortality, adjusted for age, education, race/ethnicity, income, menopausal hormone use, smoking and physical activity., Results: During 10 years of follow-up through 1997, 5201 women died. Overall, we observed a J-shaped association between BMI and mortality, with increased risk for women who were underweight, overweight or obese. The HRs and 95% confidence intervals of mortality for BMI categories of <18.5, 18.5-20.9, 21.0-23.4 (reference), 23.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9 and 35.0+ kg m(-2) were 1.43 (1.19, 1.72), 1.07 (0.98, 1.17), 1.00 (reference), 1.10 (1.00, 1.20), 1.20 (1.11, 1.31), 1.23 (1.11, 1.37), 1.60 (1.44, 1.77) and 1.92 (1.64, 2.24). There was little evidence that pre-existing conditions (heart disease, diabetes and/or cancer) or smoking history modified the past BMI and mortality relation (P=0.54 and 0.76)., Conclusions: In this large cohort of women, BMI based on technician measurements of weight and height from 10 years prior to baseline showed increased risk for mortality across the range of overweight and obesity, regardless of disease and smoking history. Observed associations between overweight, obesity and mortality in healthy individuals may also apply to persons with a history of disease or smoking.

Increased body size and lack of physical activity are associated with increased risk of several cancers, but the relations of body mass index (BMI) and physical activity to bladder cancer are poorly understood. We investigated the associations between BMI, physical activity, and bladder cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 471,760 U.S. men and women, followed from 1995 to 2003. During 3,404,642 person-years of follow-up, we documented 1,719 incident cases of bladder cancer. Compared with normal weight, obesity was associated with an up to 28% increased risk for bladder cancer. The multivariate relative risks of bladder cancer for BMI values of 18.5 to 24.9 (reference), 25.0 to 29.9, 30.0 to 34.9, and >or=35 kg/m2 were 1.0, 1.15, 1.22, and 1.28 (95% confidence interval, 1.02-1.61; P trend = 0.028). The association between BMI and bladder cancer was consistent among subgroups defined by gender, education, smoking status, and other potential effect modifiers. In contrast, physical activity showed no statistically significant relation with bladder cancer. After multivariate adjustment, including BMI, the relative risks of bladder cancer for increasing frequency of physical activity [0 (reference), <1, 1-2, 3-4, and >or=5 times a week] were 1.0, 0.85, 0.89, 0.91, and 0.87 (95% confidence interval, 0.74-1.02; P trend = 0.358), respectively. In conclusion, these findings provide support for a modest adverse effect of adiposity on risk for bladder cancer. In contrast, our results do not suggest a relation between physical activity and bladder cancer.

Background: Magnesium deficiency can cause dyslipidemia and insulin hypersecretion, which may facilitate gallstone formation. However, the effect of long-term consumption of magnesium on the risk of gallstone disease is unknown., Methods: We prospectively studied magnesium consumption and risk of gallstone disease in a cohort of 42,705 U.S. men from 1986 to 2002. Magnesium consumption was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially., Results: We documented 2,195 incident cases of symptomatic gallstones during 560,810 person-years of follow-up. The age-adjusted relative risks (RRs) for men with total magnesium intake and dietary magnesium, when the highest and lowest quintiles were compared, were 0.67 (95% confidence interval [CI] 0.59-0.77, P for trend <0.0001) and 0.67 (CI 0.59-0.76, P for trend <0.0001), respectively. After adjusting for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of total magnesium intake (RR 0.72, CI 0.61-0.86, P for trend = 0.006) and dietary magnesium (RR 0.68, CI 0.57-0.82, P for trend = 0.0006) remained significant with a dose-response relationship., Conclusions: Our findings suggest a protective role of magnesium consumption in the prevention of symptomatic gallstone disease among men.

Introduction: By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal., Methods: We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health-AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers., Results: Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily aspirin use (relative risk = 0.84, 95% confidence interval = 0.71 to 0.98)--a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer., Conclusion: Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype.

Background: Various saturated fatty acids have different effects on blood lipids and insulin secretion in experiments. The effect of long-term consumption of specific and different classes of saturated fatty acids on the risk of gallstone disease in humans is unknown., Methods: We prospectively studied consumption of saturated fatty acids and risk of gallstone disease in a cohort of 44,524 US men from 1986 to 2002. Intake of saturated fatty acids was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially., Results: During 584,679 person-years of follow-up, we documented 2350 incident cases of gallstone disease, of which 1387 cases required cholecystectomy. Compared with men in the lowest quintile of dietary intake of long-chain saturated fats, after adjustment for age and other potential risk factors, the relative risk of gallstone disease for men in the highest quintile was 1.24 [95% confidence interval (CI), 1.02, 1.50, P for trend = 0.03], and the relative risk of cholecystectomy for men in the highest quintile was 1.41 (CI, 1.09, 1.82, P for trend = 0.008). Consumption of medium-chain saturated fatty acids or short-chain saturated fatty acids was unrelated to the risk., Conclusions: Our results suggest that a higher consumption of long-chain saturated fatty acids may enhance the risk of gallstone disease in men.

Introduction: To prospectively examine the relation of total, vigorous and non-vigorous physical activity to postmenopausal breast cancer risk., Methods: We studied 32,269 women enrolled in the Breast Cancer Detection Demonstration Project Follow-up Study. Usual physical activity (including household, occupational and leisure activities) throughout the previous year was assessed at baseline using a self-administered questionnaire. Postmenopausal breast cancer cases were identified through self-reports, death certificates and linkage to state cancer registries. A Cox proportional hazards regression was used to estimate the relative risk and 95% confidence intervals of postmenopausal breast cancer associated with physical activity., Results: During 269,792 person-years of follow-up from 1987 to 1998, 1506 new incident cases of postmenopausal breast cancer were ascertained. After adjusting for potential risk factors of breast cancer, a weak inverse association between total physical activity and postmenopausal breast cancer was suggested (relative risk comparing extreme quintiles = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.21). That relation was almost entirely contributed by vigorous activity (relative risk comparing extreme categories = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.08). The inverse association with vigorous activity was limited to women who were lean (ie, body mass index <25.0 kg/m2: relative risk = 0.68; 95% confidence interval = 0.54 to 0.85). In contrast, no association with vigorous activity was noted among women who were overweight or obese (ie, body mass index > or = 25.0 kg/m2: relative risk = 1.18; 95% confidence interval = 0.93 to 1.49; p for interaction = 0.008). Non-vigorous activity showed no relation to breast cancer (relative risk comparing extreme quintiles = 1.02; 95% confidence interval = 0.87 to 1.19; p for trend = 0.86). The physical activity and breast cancer relation was not specific to a certain hormone receptor subtype., Conclusions: In this cohort of postmenopausal women, breast cancer risk reduction appeared to be limited to vigorous forms of activity; it was apparent among normal weight women but not overweight women, and the relation did not vary by hormone receptor status. Our findings suggest that physical activity acts through underlying biological mechanisms that are independent of body weight control.

Changing patterns of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) incidence worldwide suggest distinct etiologies. Although associations between fruit and vegetable intake and both ESCC and EAC have been found in multiple ecological and case-control studies, few prospective studies have investigated these associations. We prospectively examined these associations in 490,802 participants of the National Institutes of Health (NIH)-AARP Diet and Health Study using Cox models adjusted for age, alcohol intake, body mass index, cigarette smoking, education, physical activity and total energy intake. We present hazard ratios and 95% confidence intervals per serving per 1,000 calories. During 2,193,751 person years of follow-up, 103 participants were diagnosed with ESCC and 213 participants with EAC. We found a significant inverse association between total fruit and vegetable intake and ESCC risk (HR: 0.78, 95% CI: 0.67-0.91), but not EAC risk (0.98, 0.90-1.08). In models mutually adjusted for fruit and vegetable intake, the protective association with ESCC was stronger for fruits (0.73, 0.57-0.93) than for vegetables (0.84, 0.66-1.07). When we examined botanical subgroups, we observed significant protective associations for ESCC and intake of Rosacea (apples, peaches, nectarines, plums, pears and strawberries) and Rutaceae (citrus fruits). A significant inverse association between EAC and Chenopodiaceae (spinach) intake was observed. Results from our study suggest that the relation of fruit and vegetable intake and esophageal cancer risk may vary by histologic type., ((c) 2007 Wiley-Liss, Inc.)

Background: Whether national physical activity recommendations are related to mortality benefit is incompletely understood., Methods: We prospectively examined physical activity guidelines in relation to mortality among 252,925 women and men aged 50 to 71 years in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed using 2 self-administered baseline questionnaires., Results: During 1,265,347 person-years of follow-up, 7,900 participants died. Compared with being inactive, achievement of activity levels that approximate the recommendations for moderate activity (at least 30 minutes on most days of the week) or vigorous exercise (at least 20 minutes 3 times per week) was associated with a 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.68-0.78) and 32% (RR, 0.68; 95% CI, 0.64-0.73) decreased mortality risk, respectively. Physical activity reflective of meeting both recommendations was related to substantially decreased mortality risk overall (RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers (RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers (RR, 0.54; 95% CI, 0.45-0.64), normal weight (RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals (RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d (RR, 0.53; 95% CI, 0.44-0.63) and more than 2 h/d of television or video watching (RR, 0.50; 95% CI, 0.45-0.55). Engaging in physical activity at less than recommended levels was also related to reduced mortality risk (RR, 0.81; 95% CI, 0.76-0.86)., Conclusions: Following physical activity guidelines is associated with lower risk of death. Mortality benefit may also be achieved by engaging in less than recommended activity levels.

Background: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality., Methods: Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27,799 deaths were documented. In the first 5 years of follow-up, 5,985 cancer deaths and 3,451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern (components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat-saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models., Results: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 (95% CI, 0.76-0.83), 0.78 (95% CI, 0.69-0.87), and 0.83 (95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P = .04 and P < .001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged., Conclusion: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population.

Calcium and dairy foods in relation to prostate cancer were examined in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study (1995/1996-2001). Diet was assessed with a food frequency questionnaire at baseline. Multivariate relative risks and 95% confidence intervals were estimated by Cox regression. During up to 6 years of follow-up (n = 293,888), the authors identified 10,180 total prostate cancer cases (8,754 nonadvanced, 1,426 advanced, and 178 fatal cases). Total and supplemental calcium were unrelated to total and nonadvanced prostate cancer. However, a statistically nonsignificant positive association with total calcium was observed for advanced (> or = 2,000 vs. 500-<750 mg/day: relative risk (RR) = 1.25, 95% confidence interval (CI): 0.91, 1.71; p(trend) = 0.06) and fatal (> or = 1,000 vs. 500-<750 mg/day: RR = 1.39, 95% CI: 0.92, 2.09; p(trend) = 0.10) prostate cancer. Skim milk, but not other dairy foods, was associated with increased risk of advanced prostate cancer (> or = 2 vs. zero servings/day: RR = 1.23, 95% CI: 0.99, 1.54; p(trend) = 0.01). In contrast, calcium from nondairy foods was associated with lower risk of nonadvanced prostate cancer (> or = 600 vs. < 250 mg/day: RR = 0.82, 95% CI: 0.68, 0.99; p(trend) = 0.04). Although the authors cannot definitively rule out a weak association for aggressive prostate cancer, their findings do not provide strong support for the hypothesis that calcium and dairy foods increase prostate cancer risk.

Higher intakes of calcium and dairy products, a major source of dietary calcium, are reported to increase the risk of prostate cancer, potentially due to reductions in circulating vitamin D with increasing calcium intake. We prospectively examined the association of dairy product and calcium intake with prostate cancer risk in 29,509 men, including 1,910 cases, in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We also evaluated the relation of calcium intake with serum 25-hydroxy-vitamin D [25(OH)D] and 1,25-dihydroxy-vitamin D [1,25(OH)(2)D], in a Prostate, Lung, Colorectal, and Ovarian Trial substudy (n = 275). Dietary intake was assessed using a food frequency questionnaire. Baseline serum 1,25(OH)(2)D was determined by RIA. Greater intake of dairy products, particularly low-fat dairy products, was weakly associated with increased risk of prostate cancer [relative risk (RR), 1.12; 95% confidence intervals (CI), 0.97-1.30; P trend = 0.06 for >2.75 versus < or = 0.98 servings of total dairy/day; 1.23 (1.07-1.41) for low-fat dairy]. Greater dietary calcium intake was associated with increased risk of prostate cancer (RR, 1.34; 95% CI, 0.93-1.94; P trend = 0.02 for >2,000 versus <1,000 mg/day), but greater supplementary calcium intake was not associated with the risk. Associations of dairy product and dietary calcium intake were evident for nonaggressive disease (RR, 1.20; 95% CI, 0.99-1.46; P trend = 0.01 for dairy products; 1.64, 1.04-2.57; P trend = 0.002 for dietary calcium), but not aggressive disease (RR, 1.02; 95% CI, 0.81-1.28 for dairy products; 0.94, 0.49-1.80 for dietary calcium). Calcium intake was not associated with serum 25-hydroxy-vitamin D and 1,25(OH)(2)D concentration. In this large prospective study in a prostate cancer screening trial, greater dietary intake of calcium and dairy products, particularly low-fat types, may be modestly associated with increased risks for nonaggressive prostate cancer, but was unrelated to aggressive disease. Furthermore, we found no relationship between calcium intake and circulating vitamin D.

Background: Red meat and processed meat have been associated with carcinogenesis at several anatomic sites, but no prospective study has examined meat intake in relation to a range of malignancies. We investigated whether red or processed meat intake increases cancer risk at a variety of sites., Methods and Findings: The National Institutes of Health (NIH)-AARP (formerly the American Association for Retired Persons) Diet and Health Study is a cohort of approximately 500,000 people aged 50-71 y at baseline (1995-1996). Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals within quintiles of red and processed meat intake. During up to 8.2 y of follow-up, 53,396 incident cancers were ascertained. Statistically significant elevated risks (ranging from 20% to 60%) were evident for esophageal, colorectal, liver, and lung cancer, comparing individuals in the highest with those in the lowest quintile of red meat intake. Furthermore, individuals in the highest quintile of processed meat intake had a 20% elevated risk for colorectal and a 16% elevated risk for lung cancer., Conclusions: Both red and processed meat intakes were positively associated with cancers of the colorectum and lung; furthermore, red meat intake was associated with an elevated risk for cancers of the esophagus and liver.

Background: Obesity is a risk factor for postmenopausal breast cancer, but the role of the timing and amount of adult weight change in breast cancer risk is unclear., Methods: We prospectively examined the relations of adiposity and adult weight change to breast cancer risk among 99 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. Anthropometry was assessed by self-report in 1996. Through 2000, 2111 incident breast cancer cases were ascertained., Results: Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at ages 50 and 35 years, and waist-hip ratio were associated with increased breast cancer risk, particularly in women not using menopausal hormone therapy (MHT). Weight gained between age 18 years and the current age, between ages 18 and 35 years, between ages 35 and 50 years, and between age 50 years and the current age was consistently associated with increased breast cancer risk in MHT nonusers (relative risk [RR], 2.15; 95% confidence interval [CI], 1.35-3.42 for a >/=50-kg weight gain between age 18 years and the current age vs stable weight) but not in current MHT users. Risk associated with adult weight change was stronger in women with later vs earlier age at menarche (RR, 4.20; 95% CI, 2.05-8.64 for >/=15 years vs RR, 1.51; 95% CI, 1.11-2.06 for 11-12 years; P = .007 for interaction). In MHT nonusers, the associations with current BMI and adult weight change were stronger for advanced disease than for nonadvanced disease (P = .009 [current BMI] and .21 [weight gain] for heterogeneity) and were stronger for hormone receptor-positive than hormone receptor-negative tumors (P < .001 for heterogeneity)., Conclusion: Weight gain throughout adulthood is associated with increased postmenopausal breast cancer risk in MHT nonusers.

Background: Fruit and vegetable intakes have been associated with a reduced risk of colon cancer; however, in more recent studies associations have been less consistent. Statistical power to examine associations by colon site has been limited in previous studies., Methods: Fruit and vegetable intakes in relation to colon cancer risk were examined in the Pooling Project of Prospective Studies of Diet and Cancer. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated separately in 14 studies using Cox proportional hazards model and then pooled using a random-effects model. Intakes of total fruits and vegetables, total fruits, and total vegetables were categorized according to quintiles and absolute cutpoints. Analyses were conducted for colon cancer overall and for proximal and distal colon cancer separately. All statistical tests were two-sided., Results: Among 756,217 men and women followed for up to 6 to 20 years, depending on the study, 5838 were diagnosed with colon cancer. The pooled multivariable RRs (95% CIs) of colon cancer for the highest versus lowest quintiles of intake were 0.91 (0.82 to 1.01, P(trend) = .19) for total fruits and vegetables, 0.93 (0.85 to 1.02, P(trend) = .28) for total fruits, and 0.94 (0.86 to 1.02, P(trend) = .17) for total vegetables. Similar results were observed when intakes were categorized by identical absolute cut points across studies (pooled multivariable RR = 0.90, 95% CI = 0.77 to 1.05 for 800 or more versus <200 g/day of total fruits and vegetables, P(trend) = .06). The age-standardized incidence rates of colon cancer for these two intake categories were 54 and 61 per 100,000 person-years, respectively. When analyzed by colon site, the pooled multivariable RRs (95% CIs) comparing total fruit and vegetable intakes of 800 or more versus less than 200 g/day were 0.74 (0.57 to 0.95, P(trend) = .02) for distal colon cancers and 1.02 (0.82 to 1.27, P(trend) = .57) for proximal colon cancers. Similar site-specific associations were observed for total fruits and total vegetables., Conclusion: Fruit and vegetable intakes were not strongly associated with colon cancer risk overall but may be associated with a lower risk of distal colon cancer.

Background: Men are approximately 3 times more likely to develop squamous cancers of the head and neck (oral cavity, pharynx, and larynx) than women. Very few prospective studies have examined the association between cigarette smoking and cancers of the head and neck in women, even though the rates of smoking in women are increasing rapidly worldwide., Methods: The association between cigarette smoking and head and neck cancer was investigated in 476,211 participants, aged 50-71 years, of the National Institutes of Health/American Association of Retired Persons (NIH-AARP) diet and health study by using age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for these cancers., Results: Over the course of follow-up (1995 through 2000), 584 men and 175 women were diagnosed with head and neck cancer. Nonsmoking (24.4), former smoking (36.9), and current smoking (147.3) men had higher rates of incident head and neck cancer per 100,000 person-years of follow-up than women did in each equivalent category of cigarette use (non: 4.8; former: 17.2; current: 75.7). The hazard ratios associated with smoking were significantly larger in women (12.96; 95% confidence interval [CI], 7.81-21.52) than in men (5.45, 95% CI, 4.22-7.05; P for interaction: <.001) for head and neck cancer overall and also for the 3 subsites (oral cavity, oro-hypopharynx, and larynx) examined in stratified analyses. Ever-smoking accounted for 45% of head and neck cancers in men and 75% in women, assuming causality., Conclusions: Cigarette smoking is a strong risk factor for head and neck cancer in both men and women. Incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.

The authors examined the associations between fruit and vegetable intakes and risk of colorectal cancer in the NIH-AARP Diet and Health Study. Diet was assessed with a food frequency questionnaire at baseline. Relative risks and 95% confidence intervals were estimated by using the Cox proportional hazards model. During 5-year follow-up of 488,043 men and women aged 50-71 years, 2,972 incident colorectal cancer cases were identified. The respective 10th and 90th percentiles of total fruit and vegetable intake (servings/1,000 kcal per day) were 1.4 and 5.2 for men and 1.8 and 6.5 for women. Compared with that for the lowest quintile of vegetable intake, the multivariate relative risk for the highest quintile was 0.82 (95% confidence interval: 0.71, 0.94) for men and 1.12 (95% confidence interval: 0.90, 1.38) for women. Increased risk of colorectal cancer was observed for very low intake of total fruits and vegetables by men (multivariate relative risk for <1 vs. > or =2.0 servings/1,000 kcal per day = 1.26, 95% confidence interval: 1.03, 1.54). Among subgroups of vegetables, green leafy vegetables were associated with a lower risk of colorectal cancer for men (multivariate relative risk for the highest quintile vs. the lowest = 0.86, 95% confidence interval: 0.74, 0.99). Intake of fruits was not related to risk of colorectal cancer in men or women.

In most studies, body mass index (BMI) has been associated with increased risk of colorectal or colon cancer in men, but the relation is weaker and less consistent for women, possibly because of interactions with age or hormone replacement therapy. The authors examined the relation between BMI and colorectal cancer incidence in a large, prospective US cohort of 307,708 men and 209,436 women from the NIH-AARP Diet and Health Study. During follow-up of the cohort from 1995 to 2000, 2,314 cases of colorectal cancer were observed in men and 1,029 in women. BMI was related to increased risk of incident colon cancer, but not rectal cancer, for both men and women. For men, relative risks of colon cancer for a BMI of 18.5-<23, 23-<25, 25-<27.5, 27.5-<30, 30-<32.5, 32.5-<35, 35-<40, and > or = 40 kg/m(2) were 1.0 (referent), 1.11, 1.22, 1.44, 1.53, 1.57, 1.71, and 2.39, respectively (95% confidence interval: 1.59, 3.58; p-trend < 0.0005). Corresponding relative risks for women were 1.0, 1.20, 1.29, 1.31, 1.28, 1.13, 1.46, and 1.49 (95% confidence interval: 0.98, 2.25; p-trend = 0.02). BMI was related to colon cancer risk for younger (aged 50-66 years) but not older (aged 67-71 years) women. The association was not modified by hormone replacement therapy in women or physical activity in men or women.

Rates of esophageal adenocarcinoma and gastric cardia adenocarcinoma have increased, while rates of esophageal squamous cell carcinoma (ESCC) and gastric noncardia adenocarcinoma have decreased, suggesting distinct etiologies. The authors prospectively investigated the associations of alcohol and tobacco with these cancers in 474,606 US participants using Cox models adjusted for potential confounders. Between 1995/1996 and 2000, 97 incident cases of ESCC, 205 of esophageal adenocarcinoma, 188 of gastric cardia, and 187 of gastric noncardia cancer occurred. Compared with nonsmokers, current smokers were at increased risk for ESCC (hazard ratio (HR) = 9.27, 95% confidence interval (CI): 4.04, 21.29), esophageal adenocarcinoma (HR = 3.70, 95% CI: 2.20, 6.22), gastric cardia (HR = 2.86, 95% CI: 1.73, 4.70), and gastric noncardia (HR = 2.04, 95% CI: 1.32, 3.16). Assuming causality, ever smoking had population attributable risks of 77% (95% CI: 0.55, 0.89) for ESCC, 58% (95% CI: 0.38, 0.72) for esophageal adenocarcinoma, 47% (95% CI: 0.27, 0.63) for gastric cardia, and 19% (95% CI: 0.00, 0.37) for gastric noncardia. For drinkers of more than three alcoholic beverages per day, compared with those whose intake was up to one drink per day, the authors found significant associations between alcohol intake and ESCC risk (HR = 4.93, 95% CI: 2.69, 9.03) but not risk for esophageal, gastric cardia, or gastric noncardia adenocarcinoma.

Supplemental vitamin E (alpha-tocopherol) has been linked to lower prostate cancer incidence in one randomized trial and several, although not all, observational studies. The evidence regarding dietary intake of individual vitamin E isoforms and prostate cancer is limited and inconclusive, however. We prospectively examined the relations of supplemental vitamin E and dietary intakes of alpha-, beta-, gamma-, and delta- tocopherols to prostate cancer risk among 295,344 men, ages 50 to 71 years and cancer-free at enrollment in 1995 to 1996, in the NIH-AARP Diet and Health Study. At baseline, participants completed a questionnaire that captured information on diet, supplement use, and other factors. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) of prostate cancer. During 5 years of follow-up, 10,241 incident prostate cancers were identified. Supplemental vitamin E intake was not related to prostate cancer risk (for >0-99, 100-199, 200-399, 400-799, and > or = 800 IU/d versus never use: RR, 0.97, 0.89, 1.03, 0.99, and 0.97 (95% CI, 0.87-1.07) respectively; Ptrend = 0.90). However, dietary gamma-tocopherol, the most commonly consumed form of vitamin E in the United States, was significantly inversely related to the risk of advanced prostate cancer (for highest versus lowest quintile: RR, 0.68; 95% CI, 0.56-0.84; Ptrend = 0.001). These results suggest that supplemental vitamin E does not protect against prostate cancer, but that increased consumption of gamma-tocopherol from foods is associated with a reduced risk of clinically relevant disease. The potential benefit of gamma-tocopherol for prostate cancer prevention deserves further attention.

Objective: A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors., Methods: We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50-71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression., Results: During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI=0.64, 0.74) and 0.71 (95% CI=0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR=0.41; 95% CI=0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer., Conclusion: Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk.

High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.

Background: Multivitamin supplements are used by millions of Americans because of their potential health benefits, but the relationship between multivitamin use and prostate cancer is unclear., Methods: We prospectively investigated the association between multivitamin use and risk of prostate cancer (localized, advanced, and fatal) in 295,344 men enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996. During 5 years of follow-up, 10,241 participants were diagnosed with incident prostate cancer, including 8765 localized and 1476 advanced cancers. In a separate mortality analysis with 6 years of follow-up, 179 cases of fatal prostate cancer were ascertained. Multivitamin use was assessed at baseline as part of a self-administered, mailed food-frequency questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by use of Cox proportional hazards regression, adjusted for established or suspected prostate cancer risk factors., Results: No association was observed between multivitamin use and risk of localized prostate cancer. However, we found an increased risk of advanced and fatal prostate cancers (RR = 1.32, 95% CI = 1.04 to 1.67 and RR = 1.98, 95% CI = 1.07 to 3.66, respectively) among men reporting excessive use of multivitamins (more than seven times per week) when compared with never users. The incidence rates per 100,000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9, respectively, compared with 113.4 and 11.4 in never users. The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements, including selenium, beta-carotene, or zinc., Conclusion: These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer. The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation.

Background: The association between alcohol intake and risk of renal cell cancer has been inconsistent in case-control studies. An inverse association between alcohol intake and risk of renal cell cancer has been suggested in a few prospective studies, but each of these studies included a small number of cases., Methods: We performed a pooled analysis of 12 prospective studies that included 530,469 women and 229,575 men with maximum follow-up times of 7-20 years. All participants had completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RRs) for renal cell cancer were calculated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided., Results: A total of 1430 (711 women and 719 men) cases of incident renal cell cancer were identified. The study-standardized incidence rates of renal cell cancer were 23 per 100,000 person-years among nondrinkers and 15 per 100,000 person-years among those who drank 15 g/day or more of alcohol. Compared with nondrinking, alcohol consumption (> or = 15 g/day, equivalent to slightly more than one alcoholic drink per day) was associated with a decreased risk of renal cell cancer (pooled multivariable RR = 0.72, 95% confidence interval = 0.60 to 0.86; P(trend)<.001); statistically significant inverse trends with increasing intake were seen in both women and men. No difference by sex was observed (P(heterogeneity) = .89). Associations between alcohol intake and renal cell cancer were not statistically different across alcoholic beverage type (beer versus wine versus liquor) (P = .40)., Conclusion: Moderate alcohol consumption was associated with a lower risk of renal cell cancer among both women and men in this pooled analysis.

We investigated the relation between head and neck cancer risk and alcohol consumption in the NIH-AARP Diet and Health Study. During 2,203,500 person-years of follow-up, 611 men and 183 women developed head and neck cancer. With moderate drinking (up to one alcoholic drink per day) as the referent group, non-drinkers showed an increased risk of head and neck cancer (men: hazard ratio (HR) 1.68, 95% confidence interval (95% CI) 1.37-2.06; women: 1.46, 1.02-2.08). Among male and female alcohol drinkers, we observed a significant dose-response relationship between alcohol consumption and risk. The HR for consuming >3 drinks per day was significantly higher in women (2.52, 1.46-4.35) than in men (1.48, 1.15-1.90; P for interaction=0.0036). The incidence rates per 100 000 person-years for those who consumed >3 drinks per day were similar in men (77.6) and women (75.3). The higher HRs observed in women resulted from lower incidence rates in the referent group: women (14.7), men (34.4). In summary, drinking >3 alcoholic beverages per day was associated with increased risk in men and women, but consumption of up to one drink per day may be associated with reduced risk relative to non-drinking.

Background: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive., Materials and Methods: We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions., Results: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk., Conclusion: In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.

Background: Whether the intake of dietary fiber can protect against colorectal cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been inconsistent., Objective: The objective was to investigate the relation between dietary fiber and whole-grain food intakes and invasive colorectal cancer in the prospective National Institutes of Health-AARP Diet and Health Study., Design: The analytic cohort consisted of 291 988 men and 197 623 women aged 50-71 y. Diet was assessed with a self-administered food-frequency questionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up. The Cox proportional hazards model was used to estimate the relative risks (RRs) and 95% CIs., Results: Total dietary fiber intake was not associated with colorectal cancer. The multivariate RR for the highest compared with the lowest intake quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In analyses of fiber from different food sources, only fiber from grains was associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86; 95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79 (95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association with whole grain was stronger for rectal than for colon cancer., Conclusions: In this large prospective cohort study, total dietary fiber intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.

In light of recent, strong inverse findings between lifetime red wine consumption and prostate cancer among younger men, we revisited our previous cohort analysis to more thoroughly investigate red wine consumption and prostate cancer in the Health Professionals Follow-up Study (HPFS). In 1986, HPFS participants reported their average consumption of red wine, white wine, beer and liquor during the past year, and their change in alcohol consumption over the prior 10 years. Prostate cancer diagnoses were ascertained on each biennial questionnaire and confirmed by medical record review. Between 1986 and 2002, 3,348 cases of prostate cancer were diagnosed among 45,433 eligible participants. Using men who did not consume red wine as the reference, no linear trend was observed between red wine consumption and prostate cancer in the full analytic cohort (p-trend = 0.57). Among men with unchanged alcohol consumption in the prior 10 years, and those additionally <65 years of age, slightly lower risks were observed for men who consumed 4 glasses/week, resulting in a lack of linear trend. These findings suggest that red wine does not contribute appreciably to the etiology of prostate cancer., ((c) 2006 Wiley-Liss, Inc.)

Background: Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen-plus-progestin regimens remain unclear., Methods: The National Institutes of Health-AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995-1996 and 1996-1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never-use of hormone therapy., Results: In 51,312 women who never used hormones or only used estrogen-plus-progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10-14 days per cycle: RR, 0.74; 95% CI, 0.39-1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for >/=20 days per cycle: RR, 0.80; 95% CI, 0.55-1.15) had any statistically significant association with endometrial cancer. Long durations (>/=5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38-1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53-1.36) were not associated with endometrial cancer., Conclusions: Confirmation that these estrogen-plus-progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen-plus-progestin therapy., ((c) 2007 American Cancer Society.)

Obesity and menopausal estrogen therapy are established risk factors for endometrial cancer. However, the joint effects of obesity and menopausal hormone therapy on endometrial cancer risk are incompletely understood. We addressed this issue in a cohort of 103,882 women ages 50 to 71 years at baseline in 1995 to 1996. During a median of 4.6 years, which contributed to a total of 455,304 person-years of follow-up through 2000, 677 cases of endometrial cancer were ascertained. Both baseline body mass index (BMI) and adult weight gain were associated with increased endometrial cancer risk. The multivariate relative risk (RR) comparing obese with normal weight women (BMI >30 versus <25 kg/m(2)) was 3.03 [95% confidence interval (95% CI), 2.50-3.68]. Compared with women with stable weight (gained or lost <5 kg) between age 18 and baseline, women who gained >or=20 kg had a RR of 2.75 (95% CI, 1.96-3.86). Menopausal hormone therapy significantly modified the relations of BMI (P(interaction) < 0.001) and adult weight gain (P(interaction) = 0.004) to endometrial cancer risk. Compared with normal weight, the RRs for obesity were 5.41 (95% CI, 4.01-7.29) among women who never used menopausal hormone therapy, 2.53 (95% CI, 1.21-5.30) among former menopausal hormone therapy users, and 1.44 (95% CI, 1.00-2.05) among current users. Compared with a stable weight between age 18 and baseline, the RRs for weight gain of >or=20 kg among never users and ever users of menopausal hormone therapy were 5.35 (95% CI, 3.01-9.52) and 1.43 (95% CI, 0.96-2.15), respectively. We conclude that both current adiposity and adult weight gain are associated with substantial increases in the risk of endometrial cancer, with relations particularly evident among never users of menopausal hormone therapy.

Background: Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness., Methods: The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995-1996) in the National Institutes of Health-AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate-specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs)., Results: In total, 9986 incident prostate cancers were identified during 5 years of follow-up, and 173 prostate cancer deaths were ascertained during 6 years of follow-up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [>or=40 kg/m(2)] vs men in the lowest BMI category [<25 kg/m(2)]: RR, 0.67; 95% CI, 0.50-0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m(2): RR, 1.0 [referent group]; BMI 25-29.9 kg/m(2): RR, 1.25; 95% CI, 0.87-1.80; BMI 30-34.9 kg/m(2): RR, 1.46; 95% CI, 0.92-2.33; and BMI >or=35 kg/m(2): RR, 2.12; 95% CI, 1.08-4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease., Conclusions: Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer.

Background: Excessive iron intake can promote biliary cholesterol crystal formation in experimental studies. The absorption of heme iron is more complete than that of non-heme iron in humans; however, the effect of long-term consumption of heme and non-heme iron on the risk of gallstones is unknown., Objective: The objective of the study was to examine long-term iron intake in relation to the occurrence of gallstone disease., Design: We prospectively studied intakes of heme and non-heme iron and the risk of gallstone disease in a cohort of 44 758 US men from 1986 to 2002. Iron consumption was assessed by using a validated semiquantitative food-frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially., Results: We documented 2468 incident cases of symptomatic gallstones during 597 699 person-years of follow-up. The age-adjusted relative risks (RRs) for men with intakes of heme iron and non-heme iron, when the highest and lowest quintiles were compared, were 1.21 (95% CI: 1.06, 1.37; P for trend = 0.0008) and 1.02 (95% CI: 0.90, 1.16; P for trend = 0.45), respectively. After adjustment for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of heme iron intake was not significantly changed and remained significant with a dose-response relation (RR = 1.21; 95% CI: 1.03, 1.42; P for trend = 0.01), and that of non-heme iron intake was not significant (RR = 1.14; 95% CI: 0.99, 1.31; P for trend = 0.18)., Conclusion: Our findings suggest that a higher consumption of heme iron is associated with a greater risk of gallstone disease among men.

Background: Statins are commonly used cholesterol-lowering drugs that have proapoptotic and antimetastatic activities that could affect cancer risk or progression. Results from previous epidemiologic studies of the association between statin use and cancer have been inconsistent. We investigated the association of statin use with total and advanced prostate cancer, the latter being the most important endpoint to prevent., Methods: We analyzed data from an ongoing prospective cohort study of 34,989 US male health professionals who were cancer free in 1990 and were followed to 2002. Participants reported their use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis was confirmed by medical record review. Multivariable-adjusted relative risks (RRs) were estimated from Cox proportional hazards regression models. Statistical tests were two-sided., Results: During 376,939 person-years of follow-up, we ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally invasive, metastatic, or fatal). The age-standardized incidence rates of advanced prostate cancer were 38 and 89 per 100,000 person-years in current statin users and in past or never users, respectively. The multivariable-adjusted relative risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use. The associations remained after adjusting for prostate-specific antigen screening history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower with longer statin use (P(trend) = .003); compared with never use, the relative risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09)., Conclusions: In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.

Background: The long-term effect of repeated intentional weight loss and weight regain on the risk of gallstone disease in men is not clear., Methods: Participants in the Health Professionals Follow-up Study provided information on intentional weight loss during the previous 4 years in 1992. Weight cyclers were men who had intentional weight loss and weight regain. Men free of gallstone disease at baseline were followed from 1992 to 2002. On biennial questionnaires the participants reported newly diagnosed gallstone disease., Results: During 264,760 person-years of follow-up we ascertained 1222 cases of symptomatic gallstones. We examined the effect of weight cycling on the risk of gallstone disease. The multivariate relative risk of weight cyclers, compared with weight maintainers, after adjusting for potential confounding variables, including body mass index, was 1.11 (95% confidence interval [CI], 0.94-1.31) in light cyclers, 1.18 (95% CI, 0.97-1.43) in moderate cyclers, and 1.42 (95% CI, 1.11-1.81) in severe cyclers. We further examined the effect of number of cycling episodes. Among weight cyclers, the relative risk associated with having more than 1 weight cycle, compared with weight maintainers, was 1.10 (95% CI, 0.88-1.37) in light cyclers, 1.28 (95% CI, 1.03-1.59) in moderate cyclers, and 1.51 (95% CI, 1.13-2.02) in severe cyclers., Conclusions: Our findings suggest that weight cycling, independent of body mass index, may increase the risk of gallstone disease in men. Larger weight fluctuation and more weight cycles are associated with greater risk.

Background: Although previous case-control studies have observed positive associations among gonorrhea, syphilis, clinical prostatitis, and prostate cancer, many may have been susceptible to recall and interviewer biases due to their retrospective designs. Therefore, to investigate these associations without concerns of recall and interviewer biases, we conducted a large, prospective investigation in the Health Professionals Follow-up Study., Methods: In 1992, participants were asked to report their histories of gonorrhea, syphilis, and clinical prostatitis by mailed questionnaire. Prostate cancer diagnoses were ascertained by self-report on the 1994 and each subsequent biennial follow-up questionnaire and confirmed by medical record review., Results: Of the 36,033 participants in this analysis, 2,263 were diagnosed with prostate cancer between the date of return of the 1992 questionnaire and 2002. No association was observed between gonorrhea [adjusted relative risk (RR), 1.04; 95% confidence interval (95% CI), 0.79-1.36] or syphilis (RR, 1.06; 95% CI, 0.44-2.59) and prostate cancer. Overall null results were also observed between clinical prostatitis and prostate cancer (RR, 1.08; 95% CI, 0.96-1.20), although a significant positive association was observed among younger men (<59 years) screened for prostate cancer (RR, 1.49; 95% CI, 1.08-2.06; P(interaction) = 0.006)., Conclusions: Gonorrhea and syphilis do not seem to be risk factors for prostate cancer in this cohort of men with a lower burden of sexually transmitted infections. Clinical prostatitis is also unlikely to be a risk factor, although possible roles for prostatitis in younger men and asymptomatic prostatic infection and inflammation cannot be ruled out.