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The longer older men live with diabetes, the greater their risk of experiencing erectile dysfunction (ED), according to results from the Health Professionals Follow-up Study (HPFS). To examine the association [...]

Background/Objectives:: Evidence regarding the consumption of soy foods and isoflavones in relation to risk of type 2 diabetes (T2D) is scarce. Our study was to evaluate the association between soy food and isoflavone consumption and risk of T2D in US men and women. Subjects/Methods:: We followed 63?115 women in the Nurses’ Health Study (1998–2012), 79?061 women in the Nurses’ Health Study II (1999–2013) and 21?281 men in the Health Professionals Follow-Up Study (2002–2010). Diet was assessed by a validated food-frequency questionnaire and was updated every 4 years. Self-reports of incident T2D were confirmed by a validated supplementary questionnaire. Results:: During 1?966?321 person-years of follow-up, 9185 incident T2D cases were documented. After multivariate adjustment for covariates, consumption of soy foods (tofu and soy milk) was not associated with a lower T2D risk. Compared with non-consumers of soy foods, the hazard ratio (HR) was 1.00 (95% confidence interval (CI): 0.93, 1.07) for <1 serving/week and 0.93 (95% CI: 0.83, 1.03) for ?1 serving/week of soy foods (Pfor trend=0.14). In contrast, intake of total isoflavones was inversely associated with T2D risk. Comparing extreme quintiles of isoflavones, the HR was 0.89 (95% CI: 0.83, 0.96; Pfor trend=0.009). Inverse associations were also found for consumption of major individual isoflavones, including daidzein and genistein, with risk of T2D. Conclusions:: Intake of isoflavones was associated with a modestly lower T2D risk in US men and women who typically consumed low-to-moderate amounts of soy foods. These findings warrant replications in other populations with similar soy intake levels.

BACKGROUND:: To evaluate whether single-nucleotide polymorphisms (SNPs) reflecting common variation in the tumor suppressor BRCA1affect prostate cancer outcomes. Because radiation therapy (RT) induces DNA damage, we hypothesized that common variation in BRCA1has a role in progression to lethal prostate cancer, particularly in patients receiving RT. Methods:: We followed 802 men diagnosed with localized prostate cancer (cT1-T3/N0/M0) who were treated with RT in the US Health Professionals Follow-up Study (HPFS) and Physicians’ Health Study (PHS), for progression to lethal prostate cancer. Six SNPs (rs3737559, rs1799950, rs799923, rs915945, rs4474733 and rs8176305) were genotyped in HPFS to capture common variation across BRCA1. rs4474733 and rs8176305 were also evaluated in the PHS cohort. Cox proportional hazards models were used to estimate per-allele hazard ratios (HR) and 95% confidence intervals (CI) stratified by primary treatment. Results:: In the RT group (n=802), 71 men progressed to lethal disease during a mean follow-up of 12 years. We found that two SNPs, rs4473733 (HR: 0.65; 95% CI 0.42–0.99) and rs8176305 (HR: 2.03; 95% CI 1.33–3.10), were associated with lethal prostate cancer in men receiving RT. Conclusions:: Common variation in BRCA1may influence clinical outcomes in patients receiving RT for localized prostate cancer by modifying the response to RT. Our findings merit further follow-up studies to validate these SNPs and better understand their functional and biological significance.

Background/Objectives:: Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. Subjects/Methods:: We prospectively followed 75 680 women who were free of cancer at baseline in the Nurses’ Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2–4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results:: During 2 103 037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, ⩾56 g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72–1.05; P-trend: 0.06). No association was observed for peanut butter. Conclusions:: In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors.

In 1981, R. Edgar Hope-Simpson proposed that a ‘seasonal stimulus’ intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the ‘oxidative burst’ potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's ‘seasonal stimulus’.

In the past several decades, research has defined a cluster of metabolic abnormalities with insulin resistance as a major component. Key metabolic disturbances for this syndrome include dyslipidemia (low concentrations of HDL cholesterol, and elevated concentrations of triglycerides, VLDL, and small dense LDL), hypertension, chronic inflammation, procoagulation and impaired fibrinolysis. More recently, an impressive body of epidemiologic data indicates that colon cancer, and possibly some other malignancies, are associated with the insulin resistance syndrome. This evidence includes studies of determinants of the insulin resistance syndrome (obesity, abdominal distribution of adiposity, physical inactivity), metabolic consequences (type 2 diabetes, hypertriglyceridemia, hyperglycemia), and plasma or serum markers (insulin, C-peptide) in relation to colon cancer risk. The mechanism underlying these associations is unknown, but may involve the influence of hyperinsulinemia in enhancing free or bioavailable IGF-1 levels. For other cancers related to obesity, the evidence is suggestive but less firm as that for colon cancer. The role of diet on insulin resistance and hyperinsulinemia is multifactorial; future studies should focus on the comprehensive dietary pattern on insulin resistance and hyperinsulinemia as well as on cancer risk, instead of individual factors. Future studies should also be based on better measurements of insulin resistance, β-cell depletion, and insulin response to assess better which aspects of the insulin resistance are most closely related to cancer risk.

We examined the relationship between a functional polymorphism (⁶⁶⁷C→T, ala→val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma→carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.

We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.

OBJECTIVE--To examine the association between fat intake and the incidence of coronary heart disease in men of middle age and older. DESIGN--Cohort questionnaire study of men followed up for six years from 1986. SETTING--The health professionals follow up study in the United States. SUBJECTS--43 757 health professionals aged 40 to 75 years free of diagnosed cardiovascular disease or diabetes in 1986. MAIN OUTCOME MEASURE--Incidence of acute myocardial infarction or coronary death. RESULTS--During follow up 734 coronary events were documented, including 505 non-fatal myocardial infarctions and 229 deaths. After age and several coronary risk factors were controlled for significant positive associations were observed between intake of saturated fat and risk of coronary disease. For men in the top versus the lowest fifth of saturated fat intake (median = 14.8% v 5.7% of energy) the multivariate relative risk for myocardial infarction was 1.22 (95% confidence interval 0.96 to 1.56) and for fatal coronary heart disease was 2.21 (1.38 to 3.54). After adjustment for intake of fibre the risks were 0.96 (0.73 to 1.27) and 1.72 (1.01 to 2.90), respectively. Positive associations between intake of cholesterol and risk of coronary heart disease were similarly attenuated after adjustment for fibre intake. Intake of linolenic acid was inversely associated with risk of myocardial infarction; this association became significant only after adjustment for non-dietary risk factors and was strengthened after adjustment for total fat intake (relative risk 0.41 for a 1% increase in energy, P for trend < 0.01). CONCLUSIONS--These data do not support the strong association between intake of saturated fat and risk of coronary heart disease suggested by international comparisons. They are compatible, however, with the hypotheses that saturated fat and cholesterol intakes affect the risk of coronary heart disease as predicted by their effects on blood cholesterol concentration. They also support a specific preventive effect of linolenic acid intake.

Previous studies have established a relationship between low levels of social networks and total mortality, but few have examined cause specific mortality or disease incidence. This study aimed to examine prospectively the relationships between social networks and total and cause specific mortality, as well as cardiovascular disease incidence.

Abdominal obesity increases the estrogen-to-androgen ratio and may increase sympathetic nervous activity, both hypothesized to influence the development of benign prostatic hyperplasia and the severity of urinary obstructive symptoms. In 1986 and 1987, men aged 40-75 years who were participants in the Health Professionals Follow-up Study and who were without prior diagnosis of cancer or prostatectomy provided data on weight, height, and waist and hip circumferences. The men were followed for incidence of prostatectomy for benign prostatic hyperplasia up to January 1992. In addition, the frequency and severity of symptoms of urinary obstruction were assessed among respondents to a questionnaire in 1992. Among 25,892 men who provided complete information for both surgery and symptoms, 837 men had surgery for benign prostatic hyperplasia, and 2,581 of those without surgery reported frequent urinary symptoms. After adjustment for age, smoking, and body mass index, abdominal obesity was related to prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval (CI) 1.42-3.99, for those with a waist circumference > or = 43 inches (109 cm) relative to those with a waist circumference < 35 inches (89 cm); p trend < 0.0001) and with frequent urinary symptoms among those without prostatectomy (OR = 2.00, 95% CI 1.47-2.72; p < 0.0001). Body mass index, hip circumference, and waist-to-hip ratio were not associated with benign prostatic hyperplasia independently of waist circumference. These results suggest that abdominal obesity in men may increase the frequency and severity of urinary obstructive symptoms and may increase the likelihood that such obese men will undergo a prostatectomy.

A high intake of calcium, vitamin D, or specific dairy products is thought to reduce the incidence of colorectal cancer. The association of these nutrients and foods with the occurrence of colorectal adenomas, precursors of cancer, was studied in two large US cohort studies. Cases were patients with a diagnosis of adenomatous polyps of the left colon or rectum (331 men, 1986-1990; 350 women, 1980-1988), and controls were persons with endoscopic findings negative for adenoma (9,159 men and 8,585 women). After adjustment for age, total energy, family history of colorectal cancer, body mass index, alcohol consumption, folate, intake of saturated fat and fiber, indications for endoscopy, and previous endoscopy, total calcium intake was not associated with the risk for adenoma (relative risk (RR), highest vs. lowest quintile of intake: men, 1.13, 95% confidence interval (CI) 0.76-1.66; women, 1.17, 95% CI 0.81-1.69). Total vitamin D intake was unrelated to the risk for adenoma in men (RR = 1.29, 95% CI 0.87-1.93). An inverse nonsignificant association was observed in women in the 1980-1988 analyses (RR = 0.68, 95% CI 0.41-1.13, trend p = 0.09), mainly attributable to the intake of multivitamin supplements, but an analysis of 4-year data (1984-1988) using a more detailed dietary assessment showed no association with vitamin D (RR = 1.04, 95% CI 0.65-1.67). Milk consumption and intake of total fermented dairy products were not related to adenoma risk. In conclusion, the occurrence of colorectal adenoma was neither related to calcium intake nor to milk consumption, whereas vitamin D from supplements but not diet was slightly, but not significantly, inversely associated with risk among women only.

The authors evaluated the reproducibility and validity of alcohol consumption measured by a mailed, self-administered questionnaire in two large prospective studies. Subsamples of 173 women and 136 men from these cohorts completed two food-frequency questionnaires and multiple 1-week diet records (four for women and two for men) and provided a fasting blood sample. Intakes of alcohol reported over the previous year by food frequency questionnaire 2 correlated highly with intake assessed by multiple week diet records completed over this period (Spearman r = 0.90 in women and 0.86 in men). Mean daily alcohol intake as assessed by the diet records and the questionnaires was very similar. Serum high density lipoprotein cholesterol levels were significantly correlated with alcohol intakes estimated from the questionnaire (r = 0.40 in women and 0.35 in men) and for the diet records (r = 0.33 in women and 0.38 in men). Four years after completing the diet records, women were asked to report their alcohol intake of 4 years earlier; this estimate was highly correlated with the diet records (r = 0.84) and with the earlier high density lipoprotein cholesterol (r = 0.40). These data suggest that a simple self-administered questionnaire can provide useful estimates of alcohol intake over an extended period of time in subjects participating in prospective epidemiologic studies.

Obesity, android fat distribution, and other anthropometric measures have been associated with coronary heart disease in long-term prospective studies. However, fluctuations in weight due to age-related hormonal changes and changes in lifestyle practices may bias relative risk estimates over a long follow-up period. The authors prospectively studied the association between body mass index (BMI) (kg/m2), waist-to-hip ratio, and height as independent predictors of incident coronary heart disease in a 3-year prospective study among 29,122 US men aged 40-75 years in 1986. The authors documented 420 incident coronary events during the follow-up period. Body mass index, waist-to-hip ratio, short stature, and weight gain since age 21 were associated with an increased risk of coronary heart disease. Among men younger than 65, after adjusting for other coronary risk factors, the relative risk was 1.72 (95% confidence interval (CI) 1.10-2.69) for men with BMI of 25-28.9, 2.61 (95% CI 1.54-4.42) for BMI of 29.0-32.9, and 3.44 (95% CI 1.67-7.09) for obese men with BMI > or = 33 compared with lean men with BMI < 23.0. Among men > or = 65 years of age, the association between BMI and risk of coronary heart disease was much weaker. However, in this age group, the waist-to-hip ratio was a much stronger predictor of risk (relative risk = 2.76, 95% CI 1.22-6.23 between extreme quintiles). These results suggest that for younger men, obesity, independent of fat distribution, is a strong risk factor for coronary heart disease. For older men, measures of fat distribution may be better than body mass index at predicting risk of coronary disease.

Fat intake was examined in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer. Among the Nurses' Health Study cohort members who completed a food frequency questionnaire and were free of cancer in 1986, 398 were diagnosed with breast cancer during 2 years of follow-up. These cases and 798 age-matched controls (cohort members who also completed a dietary questionnaire in 1986 but did not develop breast cancer) were sent another food frequency questionnaire in 1989 inquiring about their diet in 1985. Three hundred cases and 602 controls responded to the second questionnaire. The age-adjusted analysis using the prospective (1986) questionnaire demonstrated no appreciable associations between breast cancer incidence and intakes of total fat (odds ratio (OR) between highest and lowest quintiles = 0.87; 95% confidence interval (CI) 0.54-1.40) and saturated fat (OR = 0.97; CI 0.64-1.46). The age-adjusted analysis using the retrospective (1989) questionnaire suggested positive associations between breast cancer incidence and intakes of total fat (OR = 1.43; 95% CI 0.90-2.27) and saturated fat (OR = 1.38; 95% CI 0.89-2.13). When nutrients were adjusted for total energy intake, the direction and magnitude of the differences between the prospective and retrospective analyses were similar to the analyses unadjusted for energy intake. These results suggest that case-control studies of diet and breast cancer may yield biased associations between fat intake and the risk of breast cancer.

The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one-week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period.

The role of vasectomy in the development of prostate cancer remains controversial. In particular, there has been concern about detection bias and confounding in the previously published epidemiological studies examining this hypothesis. With the goal of minimizing detection bias, we have evaluated the relation between vasectomy and prostate cancer in a population without routine prostate cancer screening.

Measures of association in prospective studies can be distorted by incomplete follow-up. Various mailing strategies were used to contact 12,233 cohort members of the Health Professionals Follow-up Study who had not responded to three successive bulk-rate mailings. Response rates were highest, 79.5% overall, from participants who were sent a certified mailing in phase 1 (63.2%), followed by a repeat certified mailing to nonrespondents (44.3%). Although altering the physical appearance of the envelope and using other postal rates were tested, certified mail was the most effective approach for reaching study members who were nonrespondents to a mailed questionnaire.

There is substantial evidence including from meta-analyses that higher dairy intake during adulthood is associated with lower risk of colorectal cancer. In contrast, little is known about the association between adolescent dairy intake and risk of colorectal neoplasia. Only two studies have previously investigated the association between dairy intake in early life and later risk of colorectal neoplasia, with conflicting results, but none used a validated dietary assessment tool to define exposure. Therefore, with our study we aimed to investigate the association between dairy intake during adolescence and the risk of colorectal adenomas later in life using data from the large, prospective female cohort Nurses’ Health Study II (NHSII) in which adolescent diet was inquired retrospectively by a validated food frequency questionnaire, and participants were followed prospectively for incidence of colorectal adenomas.

Non sono noti dati certi sulla prevalenza della disfunzione erettile (DE) nelle diverse fasce di età né sulla correlazione della DE con altre condizioni morbose. E’stata valutata l’incidenza della DE in un’ampia popolazione di professionisti (dentisti, optometristi, farmacisti ed altre categorie) mediante questionari inviati e compilati nel corso dell’anno 2000.I partecipanti erano 31.742 ed avevano un’età compresa tra 53 e 90 anni. I soggetti con carcinoma prostatico venivano esclusi poichè nel carcinoma prostatico la DE si verifica in conseguenza del trattamento (medico, radiante o chirurgico). La prevalenza della DE nei tre mesi precedenti l’invio dei questionari era del 33%. L’attività fisica era associata ad una riduzione del rischio di DE (rischio relativo 0, 7), mentre l’obesità ad un aumento dello stesso (rischio relativo 1, 3), così come alcune malattie associate. L’età influenzava la prevalenza di DE, che era 12% al di sotto dei 59 anni, 22% tra 60 e 69 anni, 30% oltre i 69 anni. Solo il 10% degli uomini oltre gli 80 anni riferivano un’attività sessuale soddisfacente o molto soddisfacente. La DE è molto frequente nella popolazione oltre i 50 anni e la sua frequenza aumenta con l’età. La frequenza della DE è influenzata dall’attività fisica e dal peso corporeo e dalla presenza di malattie associate.

Presents an abstract entitled `Epidemiology of Prostate Cancer,' from the Harvard Medical School, Brigham and Women's Hospital in Massachusetts. Importance of genetic and exogenous factors in the etiology of prostate cancer; Clarification on the relation between diet and prostate cancer; Relevance of familial factors.

Examines the roles of diet in the development of chronic diseases in the U.S. Food choices and macronutrient sources associated with reduced chronic disease risk; Information on chronic diseases like cardiovascular disease and cancer; Importance of dietary guidelines in the prevention of disease development.