A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

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.      

Race, ethnicity and benign prostatic hyperplasia in the health professionals follow-up study

PURPOSE: We examined whether the prevalence of benign prostatic hyperplasia (BPH) varies by racial or ethnic origin in a large cohort of American male health professionals. MATERIALS AND METHODS: Included in our study were 1,508 men who underwent surgery for BPH between 1986 and 1994, and 1,837 with high moderate to severe lower urinary tract symptoms assessed by the American Urological Association symptom index in 1992 or 1994. "Noncases" comprised 23,246 asymptomatic participants. Self-reported major ancestry was black in 201 men, Asian in 413, other origin in 604 and white in 25,373. White heritage was further classified as southern European in 6,408 men, Scandinavian in 2,951 and other white in 16,014. The relative risk of BPH and 95% confidence intervals (CI) adjusted for age, body mass index, alcohol consumption, smoking and physical activity were calculated by logistic regression. RESULTS: Black men were not at increased risk for BPH (relative risk 0.85, 95% CI 0.55 to 1.31) compared with white men. Asian men were less likely to have undergone BPH surgery (relative risk 0.41, 95% CI 0.21 to 0.82), although the relative risk for symptoms was similar to that of white men. White men whose major ancestry was southern European were at modestly higher risk for BPH surgery (relative risk 1.28, 95% CI 1.12 to 1.46) and symptoms (relative risk 1.34, 95% CI 1.20 to 1.50), whereas men of Scandinavian heritage were at slightly decreased risk for symptoms than those of other white heritages. CONCLUSIONS: Racial and ethnic variation is evident in the incidence of BPH surgery and symptom severity. Whether this observed variation reflects underlying biological phenomena rather than differences in symptom tolerance requires further exploration.     

Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women.

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.     

Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph).

BACKGROUND: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. METHODS: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. RESULTS: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. CONCLUSIONS: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.     

Associations between polymorphisms in the vitamin D receptor and breast cancer risk.

Biological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts.     

FTO Genotype,Vitamin D Status,and Weight Gain During Childhood

Previous evidence suggests that variants in the fat mass and obesity-associated gene (FTO) affect adiposity in an age-dependent fashion in children, and nutritional factors may modify genotype effects. We assessed the effect of FTO rs9939609 on BMI and BMI-for-age Z score changes during childhood in a population-based longitudinal study in the Brazilian Amazon and investigated whether these effects were modified by vitamin D status, an important nutritional factor related to adiposity. At baseline, 1,088 children aged <10 years had complete genotypic and anthropometric data; 796 were followed up over a median 4.6 years. Baseline vitamin D insufficiency was defined as <75 nmol/L. We observed a 0.07 kg/m²/year increase in BMI and a 0.03 Z/year increase in BMI-for-age Z score per rs9939609 risk allele over follow-up (P = 0.01). Vitamin D status significantly modified FTO effects (P for interaction = 0.02). The rs9939609 risk allele was associated with a 0.05 Z/year increase in BMI-for-age Z score among vitamin D–insufficient children (P = 0.003), while no significant genetic effects were observed among vitamin D–sufficient children. Our data suggest that FTO rs9939609 affects child weight gain, and genotype effects are more pronounced among children with insufficient vitamin D levels.