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Background Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (OR.sub.SD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (OR.sub.SD : 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (OR.sub.SD : 1.63, 95% CI 1.40-1.90) and body fat percentage (OR.sub.SD : 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (OR.sub.SD : 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; OR.sub.SD : 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (OR.sub.SD : 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk., Author(s): Mattias Johansson 1,*, Robert Carreras-Torres 1, Ghislaine Scelo 1, Mark P. Purdue 2, Daniela Mariosa 1, David C. Muller 3, Nicolas J. Timpson 4, Philip C. Haycock 4, Kevin [...]

The study aims to investigate whether levels of sex hormone-binding globulin are an appropriate determinant of an increased risk of type 2 diabetes in men and women. The results indicate that low circulating levels of globulin were found to be a strong predictor of risk of diabetes among both men and women.

The study aims to evaluate the association between modifiable lifestyle factors and the increased risk of heart failure among men. The results indicate that in the case of healthy men, maintenance of healthy lifestyle factors leads to a reduce lifetime risk of heart disease.

Two recent genome-wide association studies have independently identified a prostate cancer susceptibility locus on chromosome 10q11.2. The most significant single-nucleotide polymorphism (SNP) marker reported, rs10993994, is 57 bp centromeric of the first exon of the MSMB gene, which encodes [beta]-microseminoprotein (prostatic secretory protein 94). In this study, a fine-mapping analysis using HapMap SNPs was conducted across a [approximately equal to] 65-kb region (chr10: 51168330-51234020) flanking rs10993994 with 13 tag SNPs in 6,118 prostate cancer cases and 6,105 controls of European origin from the Cancer Genetic Markers of Susceptibility (CGEMS) project, rs10993994 remained the most strongly associated marker with prostate cancer risk [P = 8.8 x [10.sup.-18]; heterozygous odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.11-1.30; homozygous OR = 1.64, 95% CI: 1.47-1.86 for the adjusted genotype test with 2 df]. In follow-up functional analyses, the T variant of rs10993994 significantly affected expression of in vitro luciferase reporter constructs. In electrophoretic mobility shift assays, the C allele of rs10993994 preferentially binds to the CREB transcription factor. Analysis of tumor cell lines with a CC or CT genotype revealed a high level of MSMB gene expression compared with cell lines with a TT genotype. These findings were specific to the alleles of rs10993994 and were not observed for other SNPs determined by sequence analysis of the proximal promoter. Together, our mapping study and functional analyses implicate regulation of expression of MSMB as a plausible mechanism accounting for the association identified at this locus. Further investigation is warranted to determine whether rs10993994 alone or in combination with additional variants contributes to prostate cancer susceptibility. genome-wide association studies | prostate cancer genetics | CREB transcription factor

A Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was conducted to assess whether selenium and vitamin E or both are effective in preventing prostate cancer and other secondary outcomes among healthy men. Results indicated that neither of them, alone or combined, is effective in reducing the risk of prostrate cancer.

The study aims to evaluate the efficacy of long-term administration of vitamins E and C in helping to prevent prostate and total cancer in men. The results indicate that neither of the two is effective in reducing the risk of prostate or total cancer.

A study was conducted to investigate whether the long term consumption of vitamins E and C helped in reducing the risk of cardiovascular disease among men. Results indicated that neither vitamins E nor C helped reducing the risk.

A study was conducted to investigate whether the long term consumption of vitamins E and C helped in reducing the risk of cardiovascular disease among men. Results indicated that neither vitamins E nor C helped reducing the risk of cardiovascular disease among men.

The study aims to examine the effect of a combination of folic acid, Vitamin B6, and Vitamin B12 on cancer risk in women found to be at high risk of cardiovascular disease. The results indicate that combination of folic acid, Vitamin B6, and Vitamin B12 had no significant effect on the risk of cancer in women.

A study to examine the effects of vitamin B and folic acid supplements on cardiovascular diseases, especially amongst women is conducted. Findings indicate that a combined use of folic acid and B vitamin supplements is not effective in reducing the risks of cardiovascular disease among women.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.12.023 Byline: Ravi Dhingra (a)(b)(c), Howard D. Sesso (b)(d)(e), Satish Kenchaiah (a)(b)(f), J. Michael Gaziano (a)(b)(e)(g) Abstract: It is understood that coronary heart disease (CHD) is one cause of heart failure, and many risk factors are common to both entities. Hypercholesterolemia, however, being a well-recognized risk factor for CHD, has an unclear association with incident heart failure. Author Affiliation: (a) Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (b) Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (c) Department of Medicine, Alice Peck Day Memorial Hospital, Lebanon, NH (d) Department of Epidemiology, Harvard School of Public Health, Boston, MA (e) Department of Preventive Medicine, Brigham and Women's Hospital, Boston, MA (f) Division of Cardiology, University of California Irvine Medical Center, Orange, CA (g) Division of Cardiology, Brigham and Women's Hospital, Boston, MA Article History: Received 14 September 2007; Accepted 26 December 2007 Article Note: (footnote) Part of the results were presented as an abstract at the AHA annual conference on cardiovascular disease epidemiology and prevention on March 1, 2007, in Orlando, FL., The Physicians' Health Study is supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute, Bethesda, MD.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.12.023 Byline: Ravi Dhingra (a)(b)(c), Howard D. Sesso (b)(d)(e), Satish Kenchaiah (a)(b)(f), J. Michael Gaziano (a)(b)(e)(g) Abstract: It is understood that coronary heart disease (CHD) is one cause of heart failure, and many risk factors are common to both entities. Hypercholesterolemia, however, being a well-recognized risk factor for CHD, has an unclear association with incident heart failure. Author Affiliation: (a) Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (b) Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (c) Department of Medicine, Alice Peck Day Memorial Hospital, Lebanon, NH (d) Department of Epidemiology, Harvard School of Public Health, Boston, MA (e) Department of Preventive Medicine, Brigham and Women's Hospital, Boston, MA (f) Division of Cardiology, University of California Irvine Medical Center, Orange, CA (g) Division of Cardiology, Brigham and Women's Hospital, Boston, MA Article History: Received 14 September 2007; Accepted 26 December 2007 Article Note: (footnote) Part of the results were presented as an abstract at the AHA annual conference on cardiovascular disease epidemiology and prevention on March 1, 2007, in Orlando, FL.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.08.023 Byline: Luc Djousse (a), Tobias Kurth (a)(b), J. Michael Gaziano (a)(b) Abstract: Chronic kidney disease is a risk factor for heart failure (HF). Although cystatin C can detect early kidney dysfunction, limited data are available on the association between cystatin C and HF. Author Affiliation: (a) Department of Medicine, Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (b) Department of Medicine, Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Article History: Received 12 June 2007; Accepted 24 August 2007 Article Note: (footnote) The PHS is supported by grants CA-34944 and CA-40360 from the National Cancer Institute, Bethesda, MD, and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute, Bethesda, MD. Dr Djousse is principal investigator on a K01 HL-70444 from the National Heart, Lung, and Blood Institute.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.07.004 Byline: Luc Djousse (a), Jinesh Kochar (a), J. Michael Gaziano (a)(b) Abstract: Heart failure (HF) remains a major public health issue. Data on long-term trends in the incidence of HF and survival after its onset are limited. Author Affiliation: (a) Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (b) Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Article History: Received 15 February 2007; Accepted 4 July 2007

ABSTRACT Background Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin [D.sub.3] (25[OH]D), the most commonly used index of vitamin D status, is converted to the active [...]

Migrane is associated with an adverse cardiovascular risk profile and prothrombotic factors that, could increase the risk of vascular events. An objective of evaluating the association between migrane with and without aura and subsequent risk of overall and specific cardiovascular disease is presented.

Lycopene is a major carotenoid with potent antioxidant properties that may provide protection against the development of type 2 diabetes mellitus (DM). In this study we examined the association between baseline dietary intakes of lycopene, lycopene-containing foods, and the subsequent development of type 2 DM in a large prospective cohort study. We analyzed a total of 35,783 women from the United States, aged [greater than or equal to] 45 y and free from self-reported cardiovascular disease, cancer, and DM at baseline. Intakes of lycopene and total and individual tomato-based food products were assessed by a 131-item-validated semiquantitative food-frequency questionnaire. During a median follow-up of 10.2 y, 1544 cases of incident type 2 DM were documented. After adjusting for age, total energy intake, randomized treatment assignment, body mass index, and other known DM risk factors, the multivariate-adjusted relative risks and 95% CI of type 2 DM across increasing quintiles of dietary lycopene, were 1.00 (baseline), 1.10 (0.94-1.29), 1.10 (0.94-1.29), and 1.07 (0.91-1.26) (P linear trend = 0.56). Compared with women who consumed KEY WORDS: * lycopene * tomato products * intake * diabetes mellitus * epidemiology

Genetic variation in folate-regulating enzymes contributes to the risk of cardiovascular disease (CVD). The cytoplasmic serine hydroxymethyltransferase (cSHMT) enzyme is proposed to regulate a key metabolic intersection in folate metabolism. We hypothesized that a variant in cSHMT (cSHMT 1420C [right arrow] T) affects CVD risk, and that the effect depends on a linked step in the metabolic pathway catalyzed by methylenetetrahydrofolate reductase (MTHFR). A nested case-control study of incident CVD was conducted within the all-male Normative Aging Study cohort. Of the incident CVD cases, 507 had DNA samples; 2 controls/case were selected by risk set sampling (matched on age and birth year). A significant gene-gene interaction (P-values 0.0013, 0.0064) was found between MTHFR and cSHMT, and there was little or no change in the coefficients in covariate-adjusted models. The effect of MTHFR 677C [right arrow] T genotype on CVD risk varied by cSHMT 1420C [right arrow] T genotype. Among men with cSHMT 1420C [right arrow] T TT genotype, the odds ratios (OR) for CVD risk for MTHFR 677C [right arrow] T CT and TT genotypes compared with the MTHFR 677C [right arrow] T CC genotype were 3.6 (95% CI, 1.7-7.8) and 10.6 (95% CI, 2.5-46.0), respectively. Among men with the cSHMT 1420C [right arrow] T CC/CT genotype, the corresponding ORs were 1.0 (95% CI, 0.8-1.2) and 1.3 (95% CI, 0.9-1.8). Plasma total homocysteine concentrations were highest in the subgroup of men with both polymorphisms, MTHFR 677C [right arrow] T TT and cSHMT 1420C [right arrow] T TT, consistent with a higher risk of CVD in this subgroup. A more complete understanding of the molecular mechanism awaits identification of the functional effect of the polymorphism. J. Nutr. 135: 1989-1994, 2005. KEY WORDS: * homocysteine * folate * men * cardiovascular disease

A study is conducted to examine the effect of aspirin on the risk of cancer among healthy women. Results suggest that alternate day use of low-dose aspirin for an average 10 years of treatment does not lower risk of total, breast, colorectal or other site-specific cancers.

A study is conducted to test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. The data indicates that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular mortality in healthy women.

A trial was designed to evaluate the lowest dose of aspirin that would have a cardio protective effect, while minimizing gastrointestinal side effects through the use of a low dose and alternate-day administration. It was observed that aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point.

The relative contributions and joint association of physical activity and body mass index (BMI) with diabetes are examined. Combined analyses reveal that though BMI and physical inactivity are independent predictors of incident diabetes, the magnitude of the association with BMI was found greater than with physical activity.

High blood pressure may develop as a result of inflammation, according to a study of 20,525 healthy women who were followed for an average of eight years. During that time, 5,365 women developed high blood pressure and these women were more likely to have high blood levels of C-reactive protein, a marker of inflammation. Women with the highest levels of C-reactive protein had a 50% greater risk of developing high blood pressure than women with the lowest levels after adjusting for other risk factors.

Only people who have an intermediate risk for coronary artery disease should have a non-invasive test to determine whether they have the initial stages of coronary artery disease even if they have no symptoms. People with a low risk would not benefit from screening and people with a high risk would not need to be screened. The Framingham Scoring System can be used to estimate a person's risk for developing coronary artery disease.

In addition to the inverse association of dietary lycopene with various cancers, studies suggest a role for lycopene in cardiovascular disease (CVD) prevention. We determined whether the intake of lycopene or tomato-based foods is associated with the risk of CVD in a prospective cohort of 39,876 middle-aged and older women initially free of CVD and cancer. Participants completed a food-frequency questionnaire and provided self-reports of coronary risk factors. Dietary lycopene levels were divided into quintiles, and primary lycopene food sources (total tomato-based products, including tomatoes, tomato juice, tomato sauce and pizza) were categorized. During 7.2 y of follow-up, 719 CVD cases (including myocardial infarction, stroke, revascularization and CVD death) occurred. Compared with women in the 1st quintile of lycopene, those in increasing quintiles had multivariate relative risks (RR) of CVD of 1.11, 1.14, 1.15 and 0.90 (P for trend = 0.34). For the consumption of tomato-based products, women consuming 1.5 to KEY WORDS: * lycopene * cardiovascular disease * prevention * prospective studies * women

Risk factors for stroke cause ischemic changes in the cerebral white matter that may affect frontal lobe functions more than other brain functions. Therefore, stroke risk could specifically affect performance on behavioral indexes traditionally associated with frontal lobe function such as verbal fluency. The authors examined this hypothesis in 235 healthy older men (mean age = 66.41 years) who received concurrent medical and neuropsychological examinations twice at a 3-year interval. Relations between stroke risk and decline in verbal fluency, memory, and visuospatial performance were analyzed through regression, controlling for age and education. Age was associated with decline in all cognitive functions; stroke risk was associated with decline only on verbal fluency. The relation between stroke risk and fluency decline was 80% as large as that between age and fluency decline. These results suggest that stroke risk rivals the effects of aging on verbal fluency performance.

Men who have a gene that makes them metabolize alcohol slowly have a lower risk of a heart attack than men with a gene that makes them metabolize alcohol quickly. Even so, men in either group who drank moderate amounts of alcohol had a lower risk of heart attack than men who did not drink.

One or more alcoholic drinks per week appears to lower the risk of stroke. Researchers followed 22,071 doctors participating in the Physicians' Health Study. Over an average of 12 years, 679 men had a stroke. Compared to men who never drank or drank fewer than one drink per week, those who drank more had a 20% lower risk of stroke on average. The health benefit of one drink per day was still significant but more than one drink per day had no greater effect.