Showing papers by "Edward Giovannucci published in 2004"

Comparison of risk factors for colon and rectal cancer

Abstract: Predictors of colorectal cancer have been extensively studied with some evidence suggesting that risk factors vary by subsite. Using data from 2 prospective cohort studies, we examined established risk factors to determine whether they were differentially associated with colon and rectal cancer. Our study population included 87,733 women from the Nurses' Health Study (NHS) and 46,632 men from the Health Professionals Follow Up Study (HPFS). Exposure information was collected via biennial questionnaires (dietary variables were collected every 4 years). During the follow-up period (NHS: 1980 to May 31, 2000; HPFS: 1986 to January 31, 2000), we identified 1,139 cases of colon cancer and 339 cases of rectal cancer. We used pooled logistic regression to estimate multivariate relative risks for the 2 outcomes separately and then used polytomous logistic regression to compare these estimates. In the combined cohort, age, gender, family history of colon or rectal cancer, height, body mass index, physical activity, folate, intake of beef, pork or lamb as a main dish, intake of processed meat and alcohol were significantly associated with colon cancer risk. However, only age and sex were associated with rectal cancer. In a stepwise polytomous logistic regression procedure, family history and physical activity were associated with statistically significant different relative risks of colon and rectal cancer. Our findings support previous suggestions that family history and physical activity are not strong contributors to the etiology of rectal cancer. Future investigations of colon or rectal cancer should take into consideration risk factor differences by subsite.

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.

Abstract: Background: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. Methods: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. Results: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and ≥250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (Ptrend <.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; Ptrend = .02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; Ptrend <.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (Ptrend <.001) and rectum (Ptrend = .02). Conclusion: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer. © Oxford University Press 2004, all rights reserved.

Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies.

Abstract: BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.

Plasma vitamin D metabolites and risk of colorectal cancer in women.

Abstract: Objective: Experimental evidence suggests that 1,25-dihydroxyvitamin D and its precursor, 25-hydroxyvitamin D [25(OH)D], may aid in the prevention of colorectal cancer. We therefore examined risk in relation to plasma concentrations of these vitamin D metabolites. Methods: In a nested case-control study among women in the Nurses' Health Study, we identified 193 colorectal cancer cases, ages 46 to 78 years, diagnosed up to 11 years after blood collection. Two controls were matched per case on year of birth and month of blood draw. Odds ratios (OR) for risk of colorectal cancer were calculated using conditional logistic regression adjusted for body mass index, physical activity, smoking, family history, use of hormone replacement therapy, aspirin use, and dietary intakes. Results: We found a significant inverse linear association between plasma 25(OH)D and risk of colorectal cancer ( P = 0.02). Among women in the highest quintile, the OR (95% confidence interval) was 0.53 (0.27–1.04). This inverse association remained strong when limited to women ≥60 years at blood collection ( P = 0.006) but was not apparent among the younger women ( P = 0.70). Benefit from higher 25(OH)D concentrations was observed for cancers at the distal colon and rectum ( P = 0.02) but was not evident for those at the proximal colon ( P = 0.81). In contrast to 25(OH)D, we did not observe an association between 1,25-dihydroxyvitamin D and colorectal cancer, although risk was elevated among the women in the highest quintile if they were also in the lower half of the 25(OH)D distribution (OR, 2.52; 95% confidence interval, 1.04–6.11). Conclusion: From these results and supporting evidence from previous studies, we conclude that higher plasma levels of 25(OH)D are associated with a lower risk of colorectal cancer in older women, particularly for cancers at the distal colon and rectum.

A prospective study of plasma C-peptide and colorectal cancer risk in men.

Abstract: Background Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer. Methods We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided. Results Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; P(trend) =.047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; P(trend) =.02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; P(trend) =.03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was no apparent modification of risk by BMI, insulin resistance-related factors, or vigorous exercise. Conclusion Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3.

Diet and cancer prevention.

Abstract: Dietary effects are presumed to underlie many of the large international differences in incidence seen for most cancers. Apart from alcohol and a few micronutrients, however, the role of specific nutritional factors remains ill-defined. The evidence for a role of energy balance, physical inactivity, and obesity has strengthened, while for dietary fat it has weakened. Phytochemicals such as folate, lycopene and flavonoids are still the subject of active research. As the mechanisms underlying human carcinogenesis are better understood, dietary research will focus increasingly on intermediate markers such as the insulin-like growth factors and potentially carcinogenic metabolites.

Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer.

Abstract: Objective: The hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) promotes prostate epithelial cell differentiation in vitro and thus, several groups have hypothesized that men who systemically have lower levels of 1,25(OH)2D may be at increased risk for prostate cancer. To address this hypothesis, we evaluated the association of circulating concentrations of 1,25(OH)2D and its precursor 25-hydroxyvitamin D (25(OH)D) with subsequent risk of prostate cancer. Methods: Prostate cancer cases were 460 men in the Health Professionals Follow-up Study who were diagnosed through 1998 after providing a blood specimen in 1993/95. 90.2% of the cases were organ confined or had minimal extraprostatic extension. An equal number of controls who had had a screening PSA test after blood draw were individually matched to cases on age, history of a PSA test before blood draw, and time of day, season, and year of blood draw. Plasma 1,25(OH)2D and 25(OH)D concentrations were determined by radio-immunosorbant assay blindly to case–control status. Odds ratios (OR) of prostate cancer and 95% confidence intervals (CI) were estimated from conditional logistic regression models mutually adjusting for quartiles of 1,25(OH)2D and 25(OH)D concentrations and for suspected prostate cancer risk factors. Quartile cutpoints were determined separately by season of blood draw using the distributions among controls. Results: Mean concentrations of 1,25(OH)2D and 25(OH)D were slightly, but not statistically significantly (p= 0.06 and 0.20, respectively), higher in cases (34.3 ± 7.1 pg/ml and 24.6 ± 7.7 ng/ml, respectively) than in controls (33.5 ± 7.1 pg/ml and 23.9 ± 8.2 ng/ml, respectively). The OR of prostate cancer comparing men in the top to bottom quartile of 1,25(OH)2D was 1.25 (95% CI: 0.82–1.90, p-trend = 0.16). For 25(OH)D the OR of prostate cancer comparing the top and bottom quartiles was 1.19 (95% CI: 0.79–1.79, p-trend = 0.59). These findings did not vary by level of the other metabolite, age at diagnosis, family history of prostate cancer, or factors that are thought to influence 25(OH)D levels. Conclusion: In this prospective study, we did not observe an inverse association between plasma concentrations of 1,25(OH)2D or 25(OH)D and incident prostate cancer, although we cannot rule out potential effects at later stages of the disease.

A Prospective Study of Plasma Selenium Levels and Prostate Cancer Risk

Abstract: Background: Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the Physicians’ Health Study. Methods: Using plasma samples obtained in 1982 from healthy men enrolled in the study, we conducted a nested case‐ control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of prostate cancer in pre(before October 1990) and post- (after October 1990) prostate-specific antigen (PSA) screening eras were calculated using multivariable logistic regression. Results: Prediagnostic plasma selenium levels were inversely associated with risk of advanced prostate cancer (5 th versus 1 st quintile OR 0.52, 95% CI 0.28 to 0.98; Ptrend .05), even among men diagnosed after 1990 (5 th versus 1 st quintile OR 0.39, 95% CI 0.16 to 0.97). The inverse association with prostate cancer risk was observed only for case subjects with elevated baseline PSA levels (PSA >4 ng/mL, 5 th versus 1 st quintile OR 0.49, 95% CI 0.28 to 0.86; P trend .002). These inverse associations were observed in both pre- and post-PSA eras. Conclusions: The inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggests that higher levels of selenium may slow prostate cancer tumor progression. Ongoing randomized trials of selenium supplements may help to further evaluate this issue. [J Natl Cancer Inst 2004;96:696 ‐703]

Plasma and Dietary Carotenoids, and the Risk of Prostate Cancer: A Nested Case-Control Study

Abstract: The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospective Health Professionals Follow-up Study. We matched 450 incident prostate cancer cases diagnosed from 1993-1998 to 450 controls by age, time, month, and year of blood donation. Modest inverse, but not statistically significant, associations were observed among plasma alpha-carotene, beta-carotene, and lycopene concentrations, and overall risk of prostate cancer diagnosis [odds ratio (highest versus lowest quintile; OR), alpha-carotene: OR, 0.67 [95% confidence interval (CI), -0.40-1.09]; beta-carotene: OR, 0.78 (95% CI, 0.48-1.25); lycopene: OR, 0.66 (95% CI, 0.38-1.13)]. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older (OR, 0.47; 95% CI, 0.23-0.98) and without a family history of prostate cancer (OR, 0.48; 95% CI, 0.26-0.89). Combining, older age and a negative family history provided similar results (OR, 0.43; 95% CI, 0.18-1.02). Inverse associations between beta-carotene and prostate cancer risk were also found among younger participants (<65 years of age; OR, 0.36; 95% CI, 0.14-0.91; P(trend) = 0.03). Combining dietary intake and plasma data confirmed our results. We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer, which was restricted to older participants and those without a family history of prostate cancer. This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component. In addition, our findings also suggest that among younger men, diets rich in beta-carotene may also play a protective role in prostate carcinogenesis.

Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies

Abstract: Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma

Abstract: Taking aspirin regularly is associated with a reduced risk for colorectal adenoma. The greatest effect occurred at substantially higher doses than those recommended for prevention of cardiovascular...

Dietary glycemic load and risk of colorectal cancer in the Women's Health Study.

Abstract: Although diet is believed to influence colorectal cancer risk, the long-term effects of a diet with a high glycemic load are unclear. The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth. We prospectively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer. We used baseline dietary intake measurements, assessed with a semiquantitative food-frequency questionnaire, to examine the associations of dietary glycemic load, overall dietary glycemic index, carbohydrate, fiber, nonfiber carbohydrate, sucrose, and fructose with the subsequent development of colorectal cancer. Cox proportional hazards models were used to estimate relative risks (RRs). Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer (adjusted RR = 2.85, 95% confidence interval [CI] = 1.40 to 5.80, comparing extreme quintiles of dietary glycemic load; P(trend) =.004) and was associated, although not statistically significantly, with overall glycemic index (corresponding RR = 1.71, 95% CI = 0.98 to 2.98; P(trend) =.04). Total carbohydrate (adjusted RR = 2.41, 95% CI = 1.10 to 5.27, comparing extreme quintiles of carbohydrate; P(trend) =.02), nonfiber carbohydrate (corresponding RR = 2.60, 95% CI = 1.22 to 5.54; P(trend) =.02), and fructose (corresponding RR = 2.09, 95% CI = 1.13 to 3.87; P(trend) =.08) were also statistically significantly associated with increased risk. Thus, our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women.

Dietary intake of Cruciferous vegetables, Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population.

Abstract: Objective: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk.

Alcohol, One-Carbon Metabolism, and Colorectal Cancer: Recent Insights from Molecular Studies

Abstract: A growing body of evidence implicates alcohol intake as a risk factor for colorectal cancer. Until recently, most of the data were based on epidemiologic data that examined alcohol intake in relation to risk of colorectal neoplasia, but the evidence has now been broadened by recent molecular studies on mechanisms. In particular, a number of observations strongly support a role for alcohol acting through disruptions in one-carbon metabolism. Excessive alcohol intake is a fairly consistent risk factor for colorectal neoplasia in most studies, and studies show much higher risks of colorectal neoplasia in those with high alcohol and low folate than with high alcohol or low folate individually. Interactions between high alcohol-low folate and the MTHFR677TT genotype with risk of colorectal neoplasia suggest that alcohol is acting through its effects on one-carbon metabolism because the combination of high alcohol-low folate and the MTHFR677TT genotype are related to markedly elevated serum levels of homocysteine and to DNA hypomethylation. In addition, in Japanese studies, consumers of alcohol possessing the ALDH2*2 allele, who have very elevated levels of acetaldehyde, are at high risk for colorectal cancer. The relatively high prevalence of the ALDH2*2 allele may thus account for the stronger association between alcohol and colorectal neoplasia that is frequently observed in studies in Japanese populations. Further research integrating studies with more detailed data on alcohol intake levels and patterns, folate and other related nutrient status, and relevant genotypes may help clarify unresolved questions regarding the health consequences of moderate to high alcohol drinking.

Associations of Obesity with Lower Urinary Tract Symptoms and Noncancer Prostate Surgery in the Third National Health and Nutrition Examination Survey

Abstract: The authors examined the association between obesity and lower urinary tract symptoms (LUTS) in the Third National Health and Nutrition Examination Survey. This 1988-1994 US cross-sectional study included 2,797 men aged > or = 60 years whose current weight, weight at age 25 years, highest weight ever, height, waist circumference, and body mass index (BMI) were assessed. LUTS cases had at least three of these symptoms: nocturia, incomplete emptying, weak stream, and hesitancy. Controls were men without symptoms or noncancer prostate surgery. Odds ratios adjusted for age and race and weighted for selection probability were estimated by logistic regression. The odds of LUTS were lower for men who were obese at age 25 years compared with men whose BMI was normal (odds ratio = 0.49, 95% confidence interval: 0.27, 0.91). An increase in BMI between age 25 years and the highest BMI ever was positively associated with LUTS (odds ratio = 1.90, 95% confidence interval: 0.89, 4.05). Men with a larger waist circumference (> or = 102 cm) were more likely to have LUTS compared with men with a smaller waist circumference (odds ratio = 1.48, 95% confidence interval: 0.87, 2.54). Results suggest that being overweight in young adulthood may be associated with a lower prevalence of LUTS later in life, whereas weight gain and central adiposity in adulthood are possibly associated with a higher prevalence of LUTS.

A Prospective Study of Aspirin Use and the Risk of Pancreatic Cancer in Women

Abstract: Background: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses’ Health Study. Methods: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. Results: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] 1.20, 95% confidence interval [CI] 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR 1.58, 95% CI 1.03 to 2.43; P trend .01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR 1.11, 95% CI 0.70 to 1.76; four to six tablets per week: RR 1.29, 95% CI 0.70 to 2.40; seven to 13 tablets per week: RR 1.41, 95% CI 0.76 to 2.61; and >14 tablets per week: RR 1.86, 95% CI 1.03 to 3.35) (Ptrend .02). Conclusion: Extended periods of regular aspirin use appear to be associated with a statistically signi ficantly increased risk of pancreatic cancer among women. [J Natl Cancer Inst 2004;96:22‐8] Pancreatic cancer, the fourth leading cause of cancer-related mortality in the United States (1), is a rapidly fatal malignancy with limited effective treatment. Nonetheless, other than cigarette smoking, few risk factors have been consistently linked to the risk of pancreatic cancer. Clearly, further studies are needed to identify potential causes and chemopreventive agents for the disease. There is considerable evidence that nonsteroidal antiinflammatory drugs (NSAIDs), particularly aspirin, reduce the risk of several cancers and premalignant lesions. Observational and intervention studies (2) consistently demonstrate the value of these drugs as chemopreventive agents for colorectal neoplasia. Although the mechanism by which aspirin reduces the risk

Ejaculation frequency and subsequent risk of prostate cancer.

Abstract: ContextSexual activity has been hypothesized to play a role in the development of prostate cancer, but epidemiological data are virtually limited to case-control studies, which may be prone to bias because recall among individuals with prostate cancer could be distorted as a consequence of prostate malignancy or ongoing therapy.ObjectiveTo examine the association between ejaculation frequency, which includes sexual intercourse, nocturnal emission, and masturbation and risk of prostate cancer.Design, Setting, and ParticipantsProspective study using follow-up data from the Health Professionals Follow-up Study (February 1, 1992, through January 31, 2000) of 29 342 US men aged 46 to 81 years, who provided information on history of ejaculation frequency on a self-administered questionnaire in 1992 and responded to follow-up questionnaires every 2 years to 2000. Ejaculation frequency was assessed by asking participants to report the average number of ejaculations they had per month during the ages of 20 to 29 years, 40 to 49 years, and during the past year (1991).Main Outcome MeasureIncidence of total prostate cancer.ResultsDuring 222 426 person-years of follow-up, there were 1449 new cases of total prostate cancer, 953 organ-confined cases, and 147 advanced cases of prostate cancer. Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer. The multivariate relative risks for men reporting 21 or more ejaculations per month compared with men reporting 4 to 7 ejaculations per month at ages 20 to 29 years were 0.89 (95% confidence interval [CI], 0.73-1.10); ages 40 to 49 years, 0.68 (95% CI, 0.53-0.86); previous year, 0.49 (95% CI, 0.27-0.88); and averaged across a lifetime, 0.67 (95% CI, 0.51-0.89). Similar associations were observed for organ-confined prostate cancer. Ejaculation frequency was not statistically significantly associated with risk of advanced prostate cancer.ConclusionsOur results suggest that ejaculation frequency is not related to increased risk of prostate cancer.

Dietary patterns and risk of colon cancer and adenoma in a cohort of men (United States).

Abstract: BackgroundExamining the effects of dietary patterns on cancer risk may provide insights beyond the assessment of individual foods or nutrients. Design: In the health professionals follow-up cohort, associations between the ‘prudent’ and the ‘western’ dietary pattern and risk of colon cancer and adenomas were examined in 561 colon cancer cases and 1207 distal colon adenoma cases. Results: Higher prudent pattern scores were only weakly and non-significantly associated with decreased risk of colon cancer or distal colon adenoma (highest versus lowest quintile: colon cancer: multivariate adjusted relative risk (RR)=0.84 (95 confidence interval (CI)=0.64–1.10); p t rend=0.37; distal adenoma: multivariate odds ratio (OR)=0.88 (95 CI=0.73–1.08); p t rend=0.12). Our findings suggest a moderately increased risk of colon cancer and distal adenoma with higher western pattern scores (colon cancer: RR=1.27 (95 CI=0.96–1.69), p t rend=0.05; distal adenoma: OR=1.28 (95 CI=1.05–1.56), p t rend=0.01). Adding body mass index, which is positively related to western pattern and thus may be considered an intermediate endpoint between western pattern and colon cancer, attenuated associations somewhat but not substantially. Conclusion: Our data do not provide evidence for an appreciable inverse association between higher prudent pattern scores and risk of colon cancer or distal colon adenomas, but do support a moderate positive association between higher western pattern scores and risk of colon cancer or distal colon adenomas.

Dietary Folate Intake and Incidence of Ovarian Cancer: The Swedish Mammography Cohort

Abstract: Background: Mounting evidence suggests that a low intake of the water-soluble B vitamin folate is associated with breast and colorectal carcinogenesis, especially among alcohol drinkers. However, epidemiologic data specifically linking folate intake to ovarian cancer risk are limited. Methods: We examined the association between dietary folate intake (i.e., folate from food sources) and the incidence of total epithelial ovarian cancer and its subtypes by analyzing data from the Swedish Mammography Cohort, a populationbased prospective cohort of 61 084 women, aged 38 ‐76 years, who, at baseline (i.e., from 1987 to 1990), were cancerfree and had completed a food-frequency questionnaire. Through June 30, 2003, 266 incident cases of invasive epithelial ovarian cancer were diagnosed. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of ovarian cancer with 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Overall, dietary folate intake was weakly inversely associated with total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake 0.67, 95% CI 0.43 to 1.04; Ptrend .08). Among women who consumed more than 20 g of alcohol (approximately two drinks) per week, there was a strong inverse association between dietary folate intake and total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake 0.26, 95% CI 0.11 to 0.60; Ptrend .001), but among women who consumed 20 g or less of alcohol per week, there was no such association (RR for highest versus lowest quartile of intake 1.00, 95% CI 0.59 to 1.70; Ptrend .80). The absolute risk of epithelial ovarian cancer for the lowest three quartiles versus the highest quartile of folate intake was 8 per 100 000 personyears (95% CI 0 to 16 per 100 000 person-years) overall and 26 per 100 000 person-years (95% CI 10 to 42 per 100 000 person-years) among those who consumed more than 20 g of alcohol per week. The association between dietary folate intake and cancer risk did not vary substantially among subtypes of epithelial ovarian cancer. Conclusion: A high dietary folate intake may play a role in reducing the risk of ovarian cancer, especially among women who

Alcohol Intake, Drinking Patterns, and Risk of Prostate Cancer in a Large Prospective Cohort Study

Abstract: Alcohol drinking has been extensively studied in relation to prostate cancer, yet findings on the direction of the association are equivocal. Previous studies have not examined drinking patterns. Thus, the authors prospectively evaluated the associations between these factors and risk of incident prostate cancer (n = 2,479) in a cohort study of 47,843 US men (1986-1998). The men completed a questionnaire at baseline that included information on consumption of specific types of alcohol and frequency of use. The authors estimated hazard ratios using Cox proportional hazards regression for average alcohol intake and number of days per week on which alcohol was consumed stratified by average weekly intake ( or = 105 g/week). Compared with nondrinking, the hazard ratio for consumption increased slightly from an average of 5.0-14.9 g/day (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 0.94, 1.18) to 30.0-49.9 g/day (HR = 1.13, 95% CI: 0.96, 1.33), but it was not increased at > or = 50 g/day (HR = 1.00, 95% CI: 0.77, 1.31) after adjustment for recent smoking and other factors. Compared with abstainers, risk was greatest among men who consumed an average of > or = 105 g/week but who drank on only 1-2 days per week (HR = 1.64, 95% CI: 1.13, 2.38). These results suggest that moderate or greater alcohol consumption is not a strong contributor to prostate cancer risk, except possibly in men who consume large amounts infrequently.

A Prospective Study of Folate Intake and the Risk of Pancreatic Cancer in Men and Women

Abstract: Laboratory and human studies suggest that folate intake may influence the risk of some cancers. However, prospective information about the relation between folate intake and the risk of exocrine pancreatic cancer is limited. The authors examined the relation of dietary folate intake to the risk of pancreatic cancer in two large prospective US cohorts. Folate intake was assessed by food frequency questionnaire in 1984 in women and in 1986 in men. Multivariate relative risks were adjusted for age, energy intake, cigarette smoking, body mass index, diabetes, and height. During 14 years' follow-up in each cohort, 326 incident cases of pancreatic cancer were identified. Compared with participants in the lowest category of folate intake, participants in increasing 100- micro g categories of total energy-adjusted folate intake had pooled multivariate relative risks for pancreatic cancer of 1.08, 1.10, and 1.03 (95% confidence interval: 0.74, 1.43; p(trend) = 0.99). For energy-adjusted folate from food, the pooled relative risks for increasing 100- micro g categories of intake were 0.81, 0.89, and 0.66 (95% confidence interval: 0.42, 1.03; p(trend) = 0.12). There was no statistical interaction between folate intake and methionine, alcohol, fat, or caffeine. The results from these two large prospective cohorts do not support a strong association between energy-adjusted folate intake and the risk of pancreatic cancer.

The effect of long-term intake of cis unsaturated fats on the risk for gallstone disease in men: a prospective cohort study.

Abstract: Background Monounsaturated and polyunsaturated fats act as inhibitors of cholesterol cholelithiasis in animal experiments. Objective To examine the association between long-term intake of cis unsaturated fats and the incidence of gallstone disease in humans. Design Prospective population-based cohort study. Setting The Health Professional Follow-up Study. Participants 45,756 men, age 40 to 75 years in 1986, who were free of gallstone disease. Measurements Consumption of cis unsaturated fats was assessed starting in 1986 as part of the 131-item semi-quantitative food-frequency questionnaires. Questionnaires were mailed to participants every 2 years. The main outcome measure was self-reported newly diagnosed symptomatic gallstone disease. Results During 14 years of follow-up, 2323 new cases of gallstone disease were documented. After adjustment for age and other potential risk factors, the relative risk for gallstone disease among men in the highest quintile of dietary intake of cis unsaturated fats compared with men in the lowest quintile was 0.82 (95% CI, 0.69 to 0.96; P for trend = 0.006). The relative risk among men in the highest quintile of polyunsaturated fat consumption compared with men in the lowest quintile was 0.84 (CI, 0.73 to 0.96; P for trend = 0.01), and the relative risk among men in the highest quintile of monounsaturated fat consumption compared with men in the lowest quintile was 0.83 (CI, 0.70 to 1.00; P for trend = 0.01). Limitations Outcomes were restricted to men with cholecystectomy or diagnostically confirmed but unremoved symptomatic gallstones. Conclusions A high intake of polyunsaturated and monounsaturated fats in the context of an energy-balanced diet is associated with a reduced risk for gallstone disease in men. For definitions of terms used in the text, see Glossary.

Height, predictors of C-peptide and cancer risk in men

Abstract: BACKGROUND Excessive energy intake tends to increase circulating levels of insulin and free insulin-like growth factor-1 (IGF-I), which may increase risk of some cancers that are common in Western countries. However, the relative importance of these hormonal factors during pre-adulthood and adulthood is unknown. METHODS We prospectively examined height, as a marker of pre-adult IGF-I bioactivity, and modifiable adult determinants of insulin secretion, in relation to risk of cancer, particularly Western-related cancers (colon, pancreas, kidney, and aggressive prostate cancers) in 47,690 male health professionals. Information about dietary and lifestyle factors for these men was collected at baseline (1986) and was updated periodically. A C-peptide score, representing insulin secretion, was created by using body mass, physical activity, and diet in a stepwise linear regression to predict C-peptide level, in a sample of 263 cohort members. RESULTS From 1986 to 1998, we documented 3270 incident cancers (excluding the less aggressive prostate cancers). Greater body mass index, lower physical activity, and a Western dietary pattern were independent predictors of higher plasma C-peptide levels in the sample. A C-peptide score, based on these variables, was positively related to risk of Western-related cancers, but not to other cancer types in the entire cohort. Height was also only related to Western-related cancers. For Western-related cancers, 29% (95% CI: 16%, 48%) were attributed to C-peptide scores above the first decile, 30% (95% CI: 11%, 58%) to heights >or=66 inches, and 49% (95% CI: 30%, 69%) to both factors combined. For total cancers, 29% (95% CI: 16%, 46%) were attributable to both factors. CONCLUSIONS Maximal growth in the pre-adult period and hyperinsulinaemia during adulthood may largely underlie the excess risk of some cancers that are common in Western populations. A substantial proportion of these cancers may be modifiable in adulthood, through alterations in body weight, sedentary behaviour, and dietary patterns that stimulate hyperinsulinaemia.

Epoxide hydrolase polymorphisms, cigarette smoking and risk of colorectal adenoma in the Nurses' Health Study and the Health Professionals Follow-up Study.

Abstract: Microsomal epoxide hydrolase (mEH) is involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons derived from tobacco smoke and charred meat intake. Two coding region mEH variants located in exon 3 (Tyr113His) and exon 4 (His139Arg) have been described and may affect the enzyme's specific activity. We investigated these polymorphisms and tested interactions with smoking and charred meat intake in relation to risk of colorectal adenoma in two case-control studies nested in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. mEH exon 3 and exon 4 polymorphisms were not associated with overall risk of adenoma among 556 incident cases and 557 controls from the NHS or 376 prevalent cases and 725 controls from the HPFS. A statistically significant interaction was found between the exon 4 polymorphism and smoking for men (P = 0.03) and a borderline significant interaction was found between the exon 3 polymorphism and smoking for women (P = 0.06). Women having the exon 3 'rapid' Tyr/Tyr genotype were at increased risk when exposed to either > or =25 pack-years smoking [relative risk (RR) = 2.43, 95% confidence interval (CI) 1.47-4.01] or or =25 pack-years smoking (RR = 2.21, 95% CI 1.43, 3.41) or or =25 pack-years smoking were at increased risk for colorectal adenoma and that risk is related to dose of tobacco carcinogens and mEH activity level, but the results were not consistent between men and women.