Metabolic Syndrome Among Asian Indians in the United States.

INTRODUCTION: Metabolic syndrome (MetS), a clustering of cardiometabolic risk factors of type 2 diabetes and cardiovascular disease, disproportionately affects Asian Indians (AIs). We examined prevalence of MetS using 3 ethnicity-specific MetS criteria among immigrant AIs in the United States. We also examined associations between MetS and health promotion behaviors. OBJECTIVE: To present MetS prevalence estimates by the 3 ethnicity-specific criteria and investigate differences in health promotion behaviors among AIs with and without MetS to highlight the critical need for lifestyle modification strategies for this population. DESIGN: We analyzed data from a national cross-sectional study of 1037 AIs in the United States (2004-2006). We used the consensus criteria, International Diabetes Federation criteria, and modified criteria to estimate MetS prevalence. The Health Promotion Lifestyle Profile II scale measured health promotion behaviors. Bioclinical data (fasting blood glucose, triglyceride levels) were collected. Directed acyclic graphs and Likelihood Ratio Test assisted with model selection. Multiple imputation inference incorporated uncertainty due to missing data and made use of all available data. Adjusted multivariable logistic regression analysis tested for associations. RESULTS: Out of all participants, 40.3% met the consensus criteria, 34.8% met the International Diabetes Federation criteria, and 52.5% met the modified criteria. We found no statistically significant associations between engagement in health promotion measures and the prevalence of MetS and its criteria. CONCLUSION: Our study confirmed the high prevalence of MetS in the immigrant AI population in the United States. Our results showed that AIs with MetS did not exhibit an increased level of engagement in health promotion behaviors. We recommend continued refining of criteria for diagnosis and culturally suitable, age-appropriate strategies to increase engagement in healthier lifestyles among this high-risk population.

Assessment of quality of life in people living with HIV in Georgia.

The purpose of our study was to assess quality of life (QoL) among Georgian HIV-infected individuals and to examine factors associated with QoL. Our cross-sectional study sample consisted of 201 HIV-infected adult outpatients recruited at the National AIDS Center in Tbilisi, Georgia. WHOQOL-HIV-BREF was used to measure QoL. Data about other variables of interest were obtained from medical records. Modified Poisson regression with robust variance estimates was performed to create a predictive model of factors that influenced QoL. The study results showed the following factors as predictors of good general QoL: antiretroviral (ARV) treatment (prevalence ratio (PR)=2.87 (95% CI: 1.45, 5.67)); higher education level (PR = 1.51 (95% CI: 1.05, 2.17)); CD4 cells ≥200 cells/mm3 (PR = 1.83 (95% CI: 1.13, 2.94)); and age ≥40 years (PR = 1.60 (95% CI: 1.09, 2.36)). However, all factors examined were associated with at least one QoL domain. Our study suggests that HIV-infected individuals younger than 40 years and those with lower education level are more likely to have poorer QoL, while those receiving ARV treatment tend to have better QoL. This highlights the importance of educational interventions and ARV treatment in HIV patients. Future research should seek to implement additional evidence-based actions to improve QoL in this population.

Thyroid cancer incidence attributable to overdiagnosis in the United States 1981-2011.

Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981-2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20-49 and 50+ and 41.1 and 60.1% in women ages 20-49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early-stage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.

The association between selenium and other micronutrients and thyroid cancer incidence in the NIH-AARP Diet and Health Study.

BACKGROUND: Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear. METHODS: We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health - American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50-71 years in 1995-1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index. RESULTS: With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HR(Q5 vs Q1), 1.34; 95% CI, 1.02-1.76; P(trend), <0.01), we observed no evidence of an association between quintile of selenium (HR(Q5 vs Q1), 1.23; 95% CI, 0.92-1.65; P(trend), 0.26) or other micronutrient intake and thyroid cancer. CONCLUSION: Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis.

Randomization to screening for prostate, lung, colorectal and ovarian cancers and thyroid cancer incidence in two large cancer screening trials.

BACKGROUND: Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials. METHODS: We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer. RESULTS: In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR = 1.61; 95% CI: 0.96-2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR = 2.19; 95% CI: 1.07-4.47), but not subsequently (HR = 1.08; 95% CI: 0.49-2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR = 0.61; 95% CI: 0.49-0.95) but not women (HR = 0.91; 95% CI: 0.66-1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO. CONCLUSION: Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.

PTSD diagnostic validity in Veterans Affairs electronic records of Iraq and Afghanistan veterans.

OBJECTIVE: Administrative planning and policy decisions frequently rely on diagnostic data extracted from large electronic databases. However, the accuracy of this diagnostic information is uncertain. The present study examined the degree to which various diagnoses of posttraumatic stress disorder (PTSD) within Department of Veterans Affairs (VA) electronic databases were concordant with PTSD diagnostic status determined by standardized diagnostic interview. METHOD: We interviewed 1,649 veterans of the Iraq and Afghanistan wars using the PTSD Module of the Structured Clinical Interview for DSM-IV (SCID). Participants also completed other interview-based and self-report measures of psychopathology and provided consent to access their electronic medical records (EMRs). RESULTS: Concordance between database diagnosis and SCID diagnosis was 72.3% for current PTSD and 79.4% for lifetime PTSD. We observed associations between concordance status and combat exposure, PTSD symptom presentation, comorbid anxiety and depression, and psychosocial impairment. Veterans with false-negative PTSD diagnoses in the EMR were more likely to report lower levels of combat exposure, panic, and PTSD avoidance symptoms. Veterans with false-positive PTSD diagnoses in the EMR were more likely to report treatment seeking for emotional problems and less overall functional impairment. CONCLUSIONS: Although the majority of participants were concordant for PTSD status, over 25% of EMR diagnoses differed from those obtained in the diagnostic interview, with varying proportions of false positives and false negatives. Overall, those individuals with the most and least severe symptom presentations in the diagnostic interview were more likely to be accurately classified.

Sex steroid hormone levels and body composition in men.

BACKGROUND: Previous studies indicate that testosterone (T) is positively correlated with lean mass and inversely correlated with fat mass in men; however, the directionality of these associations, as well as the association with other hormones including estradiol (E2) and SHBG, is unclear. METHODS: We examined cross-sectional and longitudinal associations of E2, T, SHBG, and E2/T ratio with body composition among men ages 30 to 79 in the Boston Area Community Health/Bone Survey. Total, trunk, and appendicular lean and fat mass were measured by dual-energy x-ray absorptiometry at baseline, and weight and waist/hip circumference were measured at baseline and follow-up. Partial Pearson correlation coefficients were used to estimate the linear relationship between each body composition measure and log-transformed hormone variable. RESULTS: In cross-sectional analyses of 821 men, T, calculated free T, and SHBG were inversely correlated with fat mass, weight, body mass index, waist/hip circumference, and waist-to-hip ratio, with multivariable-adjusted correlations ranging from -0.13 to -0.37. Calculated free E2 was positively correlated with percentage total (r = .13) and trunk (r = .15) fat mass, and E2/T was positively correlated with all measures examined (r = .13-.40). There were no significant multivariable-adjusted longitudinal associations between baseline hormone levels and change in weight, body mass index, waist/hip circumference, or waist-to-hip ratio after an average follow-up of 4.8 years. CONCLUSIONS: We observed significant cross-sectional associations between hormone levels, including E2, T, and E2/T, and body composition measures in men. Longitudinal analyses showing no influence of baseline hormone levels on change in anthropometric measures imply that body composition affects hormone levels and not the reverse.

Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women.

PURPOSE: Common analgesics (aspirin, non-aspirin NSAIDs, and acetaminophen) may be associated with hormone-related cancers, possibly via effects on sex hormone and prolactin concentrations. METHODS: Between 1996 and 1999, 29,611 participants in the Nurses' Health Study II (NHSII) provided blood samples; 18,521 provided samples timed in the early follicular and mid-luteal phases of the menstrual cycle, the remainder provided untimed samples. We assessed the cross-sectional relationship between analgesic use and plasma sex hormone and prolactin concentrations among 2,034 premenopausal women, 32-54 years old, who served as controls in nested case-control studies, or participated in a within-person hormone reproducibility study in the NHSII; this included 1,700 timed and 334 untimed samples. Estrogens and progesterone were measured in timed samples; androgens and prolactin were measured in timed and untimed samples. RESULTS: In multivariable models, non-aspirin NSAIDs were positively associated with follicular free estradiol [13.5 % higher, use ≥4 days/week vs. nonusers (p = 0.04; p trend = 0.11)]; results for follicular total estradiol were similar (13.2 % higher, p = 0.06; p trend = 0.11). Acetaminophen use was inversely associated with prolactin (11.8 % lower, use 2 days/week vs. nonusers, p = 0.01, p trend = 0.04). Acetaminophen was also inversely associated with free testosterone (7.1 % lower, use 2 days/week vs. nonusers, p = 0.04; p trend = 0.04). No other associations were observed with the other hormones, or with aspirin use. CONCLUSIONS: There were no clear patterns between analgesic use and sex hormones in premenopausal women. Acetaminophen use may be modestly associated with prolactin and free testosterone. Our results do not support that analgesic use influences cancer risk through alterations in premenopausal circulating sex hormones or prolactin.

Contributors to self-reported health in a racially and ethnically diverse population: focus on Hispanics.

PURPOSE: To understand if Hispanics report health differently than other racial and ethnic groups after controlling for demographics and risk factors for poor health. METHODS: The sample (N = 5502) included 3201 women, 1767 black, 1859 white, and 1876 Hispanic subjects from the Boston Area Community Health Survey, a population-based survey of English- and Spanish-speaking residents of Boston, Massachusetts, United States, aged 30-79 years in 2002-2005. Multiple logistic regression models were used to examine the association between race/ethnicity (including interview language for Hispanics) and fair/poor self-reported health (F/P SRH) adjusting for gender, age, socioeconomic status, depression, nativity, and comorbidities. RESULTS: Compared with whites, Hispanics interviewed in Spanish were seven times as likely to report F/P SRH (odds ratio, 7.7; 95% confidence interval, 4.9-12.2) after adjusting for potential confounders and those interviewed in English were twice as likely. In analyses stratified by depression and nativity, we observed stronger associations with Hispanic ethnicity in immigrants and nondepressed individuals interviewed in Spanish. CONCLUSIONS: Increased odds of F/P SRH persisted in the Hispanic group even when accounting for interview language and controlling for socioeconomic status, age, depression, and nativity, with interview language mitigating the association. These findings have methodological implications for epidemiologists using SRH across diverse populations.

Posttraumatic stress disorder in veterans and military personnel: epidemiology, screening, and case recognition.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that affects 7-8% of the general U.S. population at some point during their lifetime; however, the prevalence is much higher among certain subgroups, including active duty military personnel and veterans. In this article, we review the empirical literature on the epidemiology and screening of PTSD in military and veteran populations, including the availability of sensitive and reliable screening tools. Although estimates vary across studies, evidence suggests that the prevalence of PTSD in deployed U.S. military personnel may be as high as 14-16%. Prior studies have identified trauma characteristics and pre- and posttrauma factors that increase risk of PTSD among veterans and military personnel. This information may help to inform prevention and screening efforts, as screening programs could be targeted to high-risk populations. Large-scale screening efforts have recently been implemented by the U.S. Departments of Defense and Veterans Affairs. Given the prevalence and potential consequences of PTSD among veterans and active duty military personnel, development and continued evaluation of effective screening methods is an important public health need.

ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association Consortium.

PURPOSE: Previous studies have examined the association between ABO blood group and ovarian cancer risk, with inconclusive results. METHODS: In eight studies participating in the Ovarian Cancer Association Consortium, we determined ABO blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios and 95 % confidence intervals were calculated in each study using logistic regression; individual study results were combined using random effects meta-analysis. RESULTS: Compared to blood group O, the A blood group was associated with a modestly increased ovarian cancer risk: (OR: 1.09; 95 % CI: 1.01-1.18; p = 0.03). In diplotype analysis, the AO, but not the AA diplotype, was associated with increased risk (AO: OR: 1.11; 95 % CI: 1.01-1.22; p = 0.03; AA: OR: 1.03; 95 % CI: 0.87-1.21; p = 0.76). Neither AB nor the B blood groups were associated with risk. Results were similar across ovarian cancer histologic subtypes. CONCLUSION: Consistent with most previous reports, the A blood type was associated modestly with increased ovarian cancer risk in this large analysis of multiple studies of ovarian cancer. Future studies investigating potential biologic mechanisms are warranted.

Associations of commonly used medications with urinary incontinence in a community based sample.

PURPOSE: We examined the association between the use of medications and the prevalence of urinary incontinence in gender specific analyses of a community based, representative sample. MATERIALS AND METHODS: A population based epidemiological study was conducted of 5,503 men and women 30 to 79 years old residing in Boston, Massachusetts (baseline data collected from 2002 to 2005). Urological symptoms were ascertained in a 2-hour, in person interview. Urinary incontinence was defined as urine leakage occurring weekly or more often during the last year. Medications used in the last month were considered current use. Associations of 20+ medications and prevalent urinary incontinence were examined using multivariate logistic regression (ORs and 95% CIs) with adjustments for known urinary incontinence risk factors. RESULTS: The prevalence of urinary incontinence in the analysis sample was 9.0% in women and 4.6% in men. For women the prevalence was highest among users of certain antihistamines (28.4%) and angiotensin II receptor blockers (22.9%). For men the prevalence was highest among angiotensin II receptor blocker (22.2%) and loop diuretic (19.1%) users. After final multivariate adjustment there were significant positive associations for certain antihistamines, beta receptor agonists, angiotensin II receptor blockers and estrogens with urinary incontinence in women (all ORs greater than 1.7), and a borderline significant association for anticonvulsants (OR 1.75; 95% CI 1.00, 3.07). Among men only anticonvulsants were associated with urinary incontinence after final adjustments (OR 2.50; 95% CI 1.24, 5.03), although angiotensin II receptor blockers showed an adjusted association of borderline significance (OR 2.21; 95% CI 0.96, 5.10). CONCLUSIONS: Although a cross-sectional analysis cannot determine causality, our analysis suggests certain medications should be further examined in longitudinal analyses of risk to determine their influence on urological symptoms.

Project VALOR: design and methods of a longitudinal registry of post-traumatic stress disorder (PTSD) in combat-exposed veterans in the Afghanistan and Iraqi military theaters of operations.

Few studies have investigated the natural history of post-traumatic stress disorder (PTSD). Project VALOR (Veterans' After-discharge Longitudinal Registry) was designed as a longitudinal patient registry assessing the course of combat-related PTSD among 1600 male and female Veterans who served in Operation Enduring Freedom (OEF) in Afghanistan or Operation Iraqi Freedom (OIF). Aims of the study include investigating patterns and predictors of progression or remission of PTSD and treatment utilization. The study design was based on recommendations from the Agency for Healthcare Quality and Research for longitudinal disease registries and used a pre-specified theoretical model to select the measurement domains for data collection and interpretation of forthcoming results. The registry will include 1200 male and female Veterans with a recent diagnosis of PTSD in the Department of Veteran Affairs (VA) electronic medical record and a comparison group of 400 Veterans without a medical record-based PTSD diagnosis, to also allow for case-control analyses. Data are collected from administrative databases, electronic medical records, a self-administered questionnaire, and a semi-structured diagnostic telephone interview. Project VALOR is a unique and timely registry study that will evaluate the clinical course of PTSD, psychosocial correlates, and health outcomes in a carefully selected cohort of returning OEF/OIF Veterans.

ABO blood group and breast cancer incidence and survival.

ABO blood type has been associated with risk and survival for several malignancies; however, data for an association with breast cancer are inconsistent. Our study population consisted of Nurses' Health Study participants with self-reported serologic blood type and/or ABO genotype. Using Cox proportional hazards regression, we examined the association between serologic blood type and incident breast cancer among 67,697 women, including 3,107 cases. In addition, we examined the association with ABO genotype in a nested case-control study of 1,138 invasive breast cancer cases and 1,090 matched controls. Finally, we evaluated the association between serologic blood type and survival among 2,036 participants with breast cancer. No clear association was seen between serologic blood type or ABO genotype and risk of total breast cancer, invasive breast cancer or breast cancer subtypes. Compared to women with blood type O, the age-adjusted incidence rate ratios for serologic blood type and total breast cancer were 1.06 (95% CI, 0.98-1.15) for type A, 1.06 (95% CI, 0.93-1.22) for AB and 1.08 (95% CI, 0.96-1.20) for B. In genetic analyses, odds ratios for invasive breast cancer were 1.05 (95% CI, 0.87-1.27) for A/O, 1.21 (95% CI, 0.86-1.69) for A/A, 0.84 (95% CI, 0.56-1.26) for A/B, 0.84 (95% CI, 0.63-1.13) for B/O and 1.17 (95% CI, 0.35-3.86) for B/B, compared to O/O. No significant association was noted between blood type and overall or breast cancer-specific mortality. Our results suggest no association between ABO blood group and breast cancer risk or survival.

Non steroidal anti-inflammatory drug use and levels of oestrogens and androgens in men.

OBJECTIVE: Studies suggest that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lower oestrogen levels in women. However, no large, population-based studies have assessed NSAID/hormone associations in men. Our objective was to examine the association between use of prescription and over-the-counter NSAIDs, and levels of oestrogens and androgens in men. DESIGN: The Boston Area Community Health Survey, an observational survey with initial data collection in 2002-2005. PATIENTS: A total of 1766 men who provided a blood sample and data on recent analgesic use. MEASUREMENTS: Adjusted geometric mean levels of androgens, oestrogens, SHBG, LH and FSH for each category of NSAID use and the per cent difference in hormone levels for users vs nonusers. RESULTS: There was no significant association between prescription/over-the-counter NSAID use and any hormone examined after adjustment for potential confounders. For example, geometric mean testosterone levels were 13·8, 13·6 and 14·2 nM in nonusers, prescription users and over-the-counter NSAID users, respectively; the corresponding levels for estradiol were 80·3, 70·4 and 79·9 pM. In stratified analyses, however, prescription NSAID use was associated with lower testosterone, estradiol and estrone levels in obese men and lower testosterone and dehydroepiandrosterone sulphate levels in inactive men. CONCLUSIONS: While overall these data do not provide strong support for an association between NSAID use and hormone levels in men, prescription NSAIDs may decrease levels of certain oestrogens and androgens in obese and inactive men.

Nonsteroidal antiinflammatory drug use and lower urinary tract symptoms: results from the Boston area community health survey.

There is evidence for a role of inflammation in the etiology of lower urinary tract symptoms (LUTS), raising the possibility that use of nonsteroidal antiinflammatory drugs (NSAIDs) may inhibit the development or progression of LUTS. The authors examined the association between use of prescription and over-the-counter NSAIDs and LUTS among 1,974 men and 2,661 women in the Boston Area Community Health Survey (2002-2005). Multivariable-adjusted logistic regression was used to estimate odds ratios and 95% confidence intervals for LUTS, voiding symptoms, storage symptoms, and nocturia. There was no clear association between use of prescription or over-the-counter NSAIDs (compared with no NSAID use) and overall LUTS, voiding symptoms, or nocturia in men or women. However, over-the-counter NSAID use was positively associated with storage symptoms in women (odds ratio = 1.37, 95% confidence interval: 1.03, 1.83), and there was a positive association between over-the-counter NSAID use and overall LUTS among women with a history of arthritis (odds ratio = 2.09, 95% confidence interval: 1.20, 3.64). These results do not provide strong support for an association between NSAIDs and LUTS. However, the associations between over-the-counter NSAID use and certain urologic symptoms, particularly among women with arthritis, and the potential mechanisms involved should be evaluated in future studies.

ABO blood group and incidence of epithelial ovarian cancer.

Previous studies have observed an association between ABO blood group and risk of certain malignancies, including ovarian cancer; however, no prospective studies of the association with ovarian cancer risk are available. Using data from 49,153 women in the Nurses' Health Study, we examined the association between ABO blood group and incidence of epithelial ovarian cancer. Study participants reported their blood type and Rh factor in 1996, and 234 women were diagnosed with incident ovarian cancer during 10 years of follow-up. We used Cox proportional hazards regression to model the incidence rate ratios (RR) and 95% confidence intervals (CI) of ovarian cancer for each blood group category. Compared to women with blood group O, women with blood group AB or B had a nonsignificant 38% increase in ovarian cancer incidence (95% CI = 0.88-2.16 for blood group AB and 0.96-1.99 for blood group B), whereas blood group A was not associated with risk (RR = 0.95, 95% CI = 0.70-1.30). Combining blood groups AB and B, we observed a statistically significant positive association with presence versus absence of the B antigen overall (RR = 1.41, 95% CI = 1.06-1.88) and for the serous invasive subtype (RR = 1.53, 95% CI = 1.08-2.17). In this large, prospective cohort of women, presence of the B antigen was positively associated with ovarian cancer incidence, whereas blood group A was not associated with risk. Additional studies are needed to confirm this association and to explore the mechanisms through which blood group may influence ovarian cancer risk.

Risk factors for ductal and lobular breast cancer: results from the nurses' health study.

INTRODUCTION: Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study. METHODS: Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. RESULTS: The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. CONCLUSIONS: These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology.

MTHFR polymorphisms in relation to ovarian cancer risk.

OBJECTIVE: Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. METHODS: We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). RESULTS: Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. CONCLUSIONS: MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings.