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A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

PDF file - 145K, Supplementary Table 1. Studies in the Ovarian Cancer Association Consortium (OCAC) are listed, as well as the abbreviation, location, type, and number of cases and controls for each study. Supplementary Table 2. The number of cases included in the analysis from each OCAC study site is listed by histologic subtype. Supplementary Table 3. Gene symbols and IDs are listed for NF-κB pathway genes that were tagged in this study, as well as chromosome position, number of SNPs tagged, and bin coverage of each gene using Hapmap or 1000 genomes as a reference. Supplementary Table 4. Reasons and numbers of samples excluded from the analysis following the sample quality control are described. Supplementary Table 5. We evaluated rs17561 and rs6785617 for interactions with known epidemiologic risk factors for risk of clear cell and LMP tumors, respectively, and report interaction p-values in the table below.

Background: Waist-to-height ratio (WHtR) has recently been found to be a useful marker of cardiovascular disease (CVD) risk in populations in developed countries; the comparison of various obesity indices, particularly WHtR, has received little study in India and other developing countries. Aim: This study aimed to compare the associations of common obesity indices, body mass index (BMI), waist circumference, waist-hip ratio (WHR), and WHtR, with cardiometabolic risk factors in a young, rural Indian population. Subjects and Methods: Anthropometric measurements and cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) were measured using standardized protocols at the baseline visit of the Longitudinal Indian Family hEalth Pilot Study, a population-based cohort study of child-bearing age women and their husbands in rural Telangana, India. Results: In comparison with most previously studied populations, this population sample (642 males and 980 females) was younger; had lower BMI; and lower rates of diabetes, hypertension, and abnormal lipids (exception of high rates of low high-density lipoprotein). With regard to each of the cardiometabolic risk factors, the associations across the obesity indices tended to be significant, but weak, and similar to each other, whereas the association with WHR was less strong. Conclusion: Although WHtR was not a better predictor of cardiometabolic risk than conventional obesity indices, in this young adult Indian population, it was equally good. This raises the prospect of using WHtR as an alternative to BMI for assessing cardiometabolic risk in Indians considering the ease with which it can be easily done and interpreted.

Background Caesarean section delivery is increasing worldwide and in India, yet little is known about the effect on infants. We examined the association between caesarean delivery and adverse infant outcomes in an Indian national survey, accounting for factors related to the mode of delivery. Methods Inverse probability weighted logistic regression analysis of the 2015–2016 India National Family Health Survey obtained adjusted ORs (aORs) and 95% CIs. Infant outcomes were maternal report of recent concomitant diarrhoea and acute respiratory infection (ARI) in infants age ≤6 mo and neonatal death. Results Of the 189 143 reported most recent singleton births, 15.4% were delivered by caesarean, 860 (3.2%) of all infants age ≤6 mo had concomitant diarrhoea and ARI and 3480 (1.8%) neonatal deaths were reported. In adjusted analysis, caesarean delivery was not associated with concomitant diarrhoea and ARI (aOR 0.96 [95% CI 0.71 to 1.32]) but was associated with neonatal death (aOR 1.19 [95% CI 1.02 to 1.39]). Conclusions Using nationally representative cross-sectional data for India, caesarean section delivery was found to be associated with neonatal death after accounting for factors associated with the mode of delivery. Prospective exploration of the relationship between caesarean delivery and adverse infant outcomes is warranted.

OBJECTIVE: African ancestry individuals are at high risk for hypertensive cardiovascular disease (CVD) and could benefit from early detection of arterial stiffening. We tested the association between the 2017 ACC/AHA hypertension categorizations, which include new blood pressure (BP) cutoffs and a definition for elevated BP, and arterial stiffness in 772 Afro-Caribbean men aged 50+ years (mean 64 years). METHODS: Arterial stiffness was assessed by brachial-ankle pulse-wave velocity (PWV) using a waveform analyzer. Hypertension groups were based on the 2017 ACC/AHA guidelines and by pharmacologic control status. Multiple linear/logistic regression was used to determine the association of PWV with BP and hypertension. RESULTS: Mean(SD) PWV was 1609(298) cm/s and was independently correlated with age, systolic BP, pulse, diabetes, height, and alcohol intake (all P

Consanguineous marriage (CM) has been linked to spontaneous abortion (SAB), although studies have largely been cross-sectional and likely underestimated early loss. We aimed to determine the relationships between CM and SAB in a prospective pregnancy cohort study in Telangana State, India. Data from 661 participants aged 15–35 years in the Longitudinal Indian Family hEalth (LIFE) study actively followed for pregnancy and pregnancy loss were analyzed. SAB was classified as early (

Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m2). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm3)]. Serum DKK1 was positively correlated with BMI (r = 0.20; P = 0.01), waist circumference (r = 0.15; P = 0.046), DXA total-body adiposity (r = 0.24; P = 0.003), and DXA trunk adiposity (r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density (r = −0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.

Background: Adipose tissue (AT) distribution, which differs by race/ethnicity, can differentially impact risk for cardiometabolic disease. Traditional analyses using AT volumes tend to place all ATs in a regression model, estimating an increase in one AT volume while “holding other volumes constant”; however, the compositional nature of the data suggests the other ATs cannot remain constant. Compositional data analysis (CODA) methods eliminate this concern by comparing logratios of components. CODA was designed for analyses of data like those of body composition , but has yet to be used in this field. We demonstrate the use of CODA for the comparison of visceral AT (VAT) and subcutaneous AT of the abdomen (ASAT) and thigh (TSAT) with prevalence of cardiometabolic diseases. Methods: This cross-sectional analysis used 615 African Caribbean men from Tobago aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). AT volumes were obtained from CT scans of the abdomen (VAT and ASAT) and of the mid-thigh (TSAT). An additive log2 ratio transformation was applied to the ATs to generate the VAT, ASAT, and TSAT component effects relative to the other tissues captured in the respective CT scan. Ordinal logistic regression analyses were performed for increasing hypertension or glucose impairment categories (defined in Table) after adjustment for age, disease status, and lifestyle factors. Results: After full adjustment (Table), a 2-fold higher ASAT volume (relative to other abdominal tissues) was associated with higher odds, and a 2-fold higher TSAT volume (relative to other thigh tissues) was associated with lower odds, of being in a higher hypertension category. After BMI adjustment, no AT was associated with glucose impairment category. VAT was not a significant predictor for either outcome in African Ancestry men. Conclusion: CODA methods, which avoid problematic assumptions made in traditional analyses, found significant and opposing associations of TSAT and ASAT with hypertension categories in African Ancestry men.

Background: While overall obesity remains a major risk factor for cardiometabolic diseases, the location of stored fat is also thought to play a role. In addition to fat storage in ectopic sites, the density of fat, a marker of fat quality, is emerging as a novel risk factor for cardiometabolic diseases. Previous studies have focused primarily on visceral (VAT) and abdominal subcutaneous (SAT) adipose tissue density and in predominantly white cohorts; however, studies in populations of African ancestry who are at higher risk of cardiometabolic diseases are lacking. Additionally, information is lacking on associations of density of other relevant ectopic fat depots, such as intermuscular adipose tissue (IMAT), with cardiometabolic risk factors. Methods: We investigated whether VAT, SAT, or thigh IMAT densities were associated with cardiometabolic measures in 648 black men aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). Adipose tissue volume (cm 3 ) and density (Hounsfield units, HU) was measured in the abdomen (between L4 and L5) and mid-thigh from computed tomography scans. Cardiometabolic measures, including blood pressure, fasting serum glucose and insulin homeostasis, and serum lipids (N=476), were transformed as needed and used as outcomes in multiple linear regression models adjusting for age, lifestyle factors, medication use (antihypertensive, antidiabetic, or lipid-lowering), and corresponding fat depot volume. Results: After adjustment (Table), VAT, SAT, and IMAT densities were significantly associated with fasting insulin, insulin resistance, and lipids. Results remain similar after adjustment for BMI instead of fat volume and in a sensitivity analysis excluding those taking relevant medications. Conclusion: As reported in other studies, in our study among African ancestry individuals VAT and SAT were associated with several cardio-metabolic risk factors. Importantly, our findings suggest that thigh IMAT density may be a novel predictor of cardiometabolic risk in African ancestry men.

BACKGROUND Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. METHODS HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA

Aim. Falls are an important contributor to loss of function, morbidity, and mortality in elders. Little is known about falls in Indian populations. The objective of this cross-sectional report was to identify the prevalence and correlates of falls in a cohort of 562 rural southern Indian men and women. Methods. Risk factors included demographics, anthropometrics, self-reported health, medical history, physical function, vision, depression, and lifestyle. Odds ratios were calculated using logistic regression. Results. 71 (13%) subjects reported at least 1 fall in the past year. Prevalence was higher among women (17%) than men (8%), P=0.003. Sex and age showed significant interaction (P=0.04) whereby falls prevalence increased with age among women but decreased among men. Correlates of falls among men included a history of osteoarthritis (OA) (odds ratio (OR): 6.91; 95% CI: 1.4–33.1), depression (OR:9.6; 3.1–30.1), and greater height (OR per 1 standard deviation increase: 2.33; 1.1–5.1). Among women, poor physical performance (OR: 3.33; 1.13–9.86) and history of cardiovascular disease (CVD) (OR: 2.42; 1.01–5.80) were independently associated with falls. Implications. Prevalence of falls in elderly South Indians was lower than published reports from western countries and likely reflects low exposure to fall risks. Patterns with age differed in men and women and may reflect sex differences in the accuracy of age recall. Presence of comorbidities specifically OA, CVD, and depression was independent correlate of falling.

The natural history and mortality of type 1 diabetes in adolescents in Africa is not well characterized. Our aim is, therefore, to describe these characteristics for cases in the Rwanda Life For a Child (LFAC) program. Participants (≤25 years old) were the first 500 children and youth enrolled in the Rwanda LFAC program from 2004 to 2012. Clinical and demographic data were extracted from LFAC forms, and vital status was evaluated as of November 1, 2011. For the first 500 participants, 5-year survival was 93.8% while crude mortality was 13.9/1000 (95% CI 9.0–20.6/1000) person years of diabetes. However, since vital status is unknown for 134 participants, mortality could be as high as 40.2/1000 person years of diabetes if all missing cases died. Mortality was directly associated with age at diagnosis, and inversely to calendar year of first visit, BMI, and monitoring frequency. Hypertension prevalence reached 46% by 2012. Mortality rates associated with type 1 diabetes in Rwanda are similar to those in other African countries, but higher than rates in developed countries. Delayed diagnosis may contribute to excess mortality risk, but recent improvements in survival suggest that advancements are being made. Hypertension and loss to follow-up need to be addressed.

Objectives To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. Methods The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87). Results Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. Conclusions These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.

BACKGROUND fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations. METHODS in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy. RESULTS one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models. CONCLUSIONS our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.

Context: Acute infections of eyes, ears, skin, and others are a common cause of morbidity in under-five children. The overall burden of other infections and their risk factors is not known. Evidence Acquisition: Available literature was searched comprehensively using PubMed for acute infections (except acute respiratory and diarrheal diseases) using the relevant medical subject heading terms. Extracted articles were independently reviewed against inclusion/ exclusion criteria and rated for quality. 10 articles were abstracted and reviewed to identify the reported prevalence and risk factors for acute infections among children. Results: The pooled prevalence of infections (not including acute respiratory and diarrhea) between 2002 and 2013 was 18.42 (95% confidence interval: 9.30-30.62), with reported range of 3.7-50.8%. The significantly positively associated factors reported in single studies were young age of the child, malnutrition, poor breastfeeding, low socio-economic status, animal rearing near household and mothers’ illiteracy for independent morbidities. Conclusion: The evidence on risk factors including breastfeeding, vaccination, age, and sex that predispose under-five Indian children to different infections is inconclusive. There is a need to conduct more studies on acute infections other than acute respiratory and diarrhea, to establish their determinants in Indian children. Key words: Ear infection, Eye infection, India, Meta-analysis, Prevalence, Risk factors, Skin infection, Systematic review, Under-five children

We sought to identify factors associated with mode of delivery in a peri-urban Indian population with a high cesarean section rate. Poisson regression with robust error variance was applied to model factors associated with cesarean compared to vaginal delivery in a prospective, preconception pregnancy cohort study in Telangana State, India. Adjusted relative risks and 95% confidence intervals from multivariable models are presented. Among 1164 singleton births between 2010 and 2015, 46% were delivered by cesarean. In multiparous women (n = 674), prior cesarean delivery (4.2, 3.2–5.6), prior twin delivery (1.4, 1.1–1.9), diagnosis of hypertension (1.4, 1.0–2.0), or preeclampsia (3.5, 2.1–5.7) in a prior pregnancy independently increased the risk of cesarean. Prepregnancy overweight/obesity (1.4, 1.0–1.9), a composite of prenatal complications (1.3, 1.0–1.7), a composite of labor complications (1.5, 1.0–2.3), nonreassuring fetal heart rate (2.3, 1.3–4.1), and breech position (2.6, 1.4–5.0) also increased the cesarean risk. Among nulliparous women (n = 233), cephalo–pelvic disproportion (1.9, 1.2–3.0), a composite of labor complications (2.9, 1.8–4.9), and breech position (3.4, 1.9–6.2) increased the risk of cesarean. The high rate of cesarean delivery in this peri-urban Indian population is attributed to history of pregnancy complications, history of prior cesarean, prepregnancy body mass index, and medical indications at delivery.

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. Significance: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene. See related commentary by Choi and Brown, p. 439

Background Previous studies have found a relationship between cesarean section delivery and adverse outcomes in the offspring, partially attributing these findings to differential development of immunity in infants delivered by cesarean compared to vaginal delivery. The purpose of this study is to determine whether cesarean section delivery is associated with higher reports of adverse short-term infant health outcomes in a peri-urban Indian population. Methods Data from a prospective pregnancy cohort study in a peri-urban region of Telangana State, India, were analyzed to assess the association between mode of delivery, cesarean section or vaginal, and maternal report of recent infant diarrhea and/or respiratory symptoms at a 6 month follow-up visit. Inverse probability weights were applied to log-binomial regression models to account for maternal pre-pregnancy, prenatal, and labor and delivery factors. Results Of the 851 singleton infants delivered between 2010 and 2015, 46.7% were delivered by cesarean. Cesarean delivery was not associated with an increased report of infants having one or more of the outcomes (diarrhea, respiratory infection, or difficulty breathing) at 6 months (adjusted risk ratio 0.89, 95% confidence interval 0.76–1.03), nor was it associated with infants having a more severe outcome of comorbid diarrhea and respiratory infection (adjusted risk ratio 1.08, 95% confidence interval 0.58–2.04). Conclusion Unlike findings in Western populations, in this peri-urban Indian population, cesarean delivery was not associated with higher reports of short-term adverse gastrointestinal or respiratory infant outcomes after accounting for pre-delivery maternal factors. Future research in this cohort could elucidate whether mode of delivery is associated with other adverse outcomes later in childhood. Electronic supplementary material The online version of this article (10.1186/s12887-018-1324-3) contains supplementary material, which is available to authorized users.

Background: African ancestry populations are at the epicenter of the obesity and diabetes epidemic. Secreted frizzled-related protein 5 (SFRP5) is a novel adipokine and Wnt pathway modulator which is thought to be inversely related with adiposity and diabetes risk, however data in humans is conflicting. Therefore, we examined the association of SFRP5 with parameters of obesity and insulin resistance among an African ancestry population. Methods: We measured fasting serum SFRP5 in a pilot study of 139 elderly Afro-Caribbean men (mean age 71.7years, mean BMI 27.6 kg/m2). These men represented a random subset of a population-based study comprising ∼3000 African ancestry men with anthropometrics, DXA measured adiposity, and fasting morning blood collections for biomarker analysis. SFRP5 was measured in duplicate in previously unthawed serum with ELISA. Results: Using Pearson correlations, we found SFRP5 level to be positively associated with age (R = 0.18, p = 0.03) and negatively associated with BMI (R = - 0.14, p = 0.09), waist circumference (R = - 0.18, p = 0.02) and DXA trunk fat (R = - 0.24, p = 0.003), independent of age. Among nondiabetics (N=87), SFRP5 was inversely associated with fasting insulin levels (R = - 0.21, p= 0.04) and to some extent with HOMA-IR (R = -0.20, p = 0.06), independent of age and BMI. However, after adjustment for age and waist circumference, the associations between SFRP5 and fasting serum insulin and HOMA-IR were no longer significant. Conclusion: Our findings suggest that among African ancestry men, SFRP5 might have a beneficial role against general and central obesity. Our findings also suggest that the link between SFRP5 and diabetes risk in African Ancestry men may be explained by its correlation with central adiposity. Additional larger studies among African ancestry populations are needed to explore this novel biomarker along with its temporal relationship with clinically relevant metabolic outcomes. Disclosure H. Ali: None. J.M. Zmuda: None. R. Cvejkus: None. E.E. Kershaw: Consultant; Self; Regeneron Pharmaceuticals, Inc.. A.L. Kuipers: None. C.H. Bunker: None. I. Miljkovic: None.

The wingless (Wnt) pathway is known to regulate many human systems, including embryonic development, bone mineralization, and cancer. There is emerging basic research evidence that the Wnt pathway is also involved in angiogenesis, atherosclerosis, and vascular damage repair. However, there have been no studies of the Wnt pathway and cardiovascular disease (CVD) in human populations. In a cohort of Afro-Caribbean men (the Tobago Health Study (THS)), we previously identified a potentially functional coding mutation (Ala64Thr) in the Frizzled-1 ( FZD1 ) gene, which acts as a co-receptor with the low-density lipoprotein receptor protein (LRP) to initiate the Wnt signaling cascade. This mutation has a carrier frequency of ~4% in the THS and additional studies reported in the 1000 genomes project have found similar frequencies in other predominantly West African populations. In order to investigate the phenotypic consequences of this Wnt pathway mutation on subclinical CVD, we measured carotid artery wall traits using B-mode ultrasonography in 64 Ala64Thr mutation carriers and 395 controls from the THS. For this analysis, carotid artery measures of interest included carotid plaque prevalence, and common carotid mean intima-media thickness (IMT), inter-adventitial diameter (IAD), and lumen diameter (LD). We assessed differences in carotid traits by Ala64Thr status using multiple linear regression adjusting for CVD risk factors, including age, BMI, smoking, hypertension, diabetes, alcohol intake, physical activity, and sedentary behavior. Men were aged 64 years and were overweight (BMI: 27.5kg/m 2 ), on average. Prevalence of hypertension and type 2 diabetes is high in this sample (66% and 24%, respectively). Men with Ala64Thr tended to be older and had higher prevalence of hypertension than non-carriers (P1/3 of a SD greater LD than non-carriers (P=0.01). The effect magnitude of this mutation was similar for IAD, though not statistically significant (P=0.08). There was no significant difference in carotid IMT or plaque prevalence. While this mutation is not expected to be severely deleterious using in silico prediction software, Ala64 is highly conserved and located in a putative signaling peptide sequence. Carriers of a low frequency FZD1 coding mutation show greater remodeling of the carotid artery compared to non-carriers, suggesting that the Wnt pathway may be involved in vascular changes that occur early in the atherosclerotic disease process.

BACKGROUND The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation. METHODS Prostate sections were screened by immunohistochemistry for the expression of HHV-8 proteins K8.1 and LANA-1 and for presence of B cells (CD20) and macrophages (CD68). RESULTS HHV-8 antigen expression representing lytic and latent infections was seen in 73.9% of prostates from HHV-8 seropositive subjects. Latent infections were seen predominantly in glandular epithelia whereas lytic gene expression was seen mainly in macrophages in prostate stroma. Macrophage infiltrates were significantly increased in sections expressing HHV-8 proteins. CONCLUSION HHV-8 establishes a chronic latent infection in the prostate, which is associated with an increased macrophage infiltrate.

Background: Acute diarrhea accounts for a huge burden of infectious diseases in under-five children. Objective: This systematic review was carried out to study the prevalence and associated risk factors of diarrhea among Indian children aged

Objective Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. Methods Longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [intermuscular fat (mm2) and skeletal muscle density as a measure of intramuscular fat (mg/cm3)] were examined in 1515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. Results During an average of 6.2 years of follow-up, an age-related increase in intermuscular fat and a decrease in skeletal muscle density were observed (all P

Aim The Mobility and Independent Living in Elders Study (MILES) was established in 2012 to estimate the prevalence, incidence, and risk factors for disability and age-related disease in rural older Indians. Here we describe the main goals of MILES, the essential elements of its design and examinations, and the initial findings from the baseline visit. Methods A random sample of 562 men and women aged ≥60 years was enrolled from the Medchal region in Telangana State. Baseline examination consisted of two separate clinical visits, and included measurements of blood pressure, anthropometry, physical function, peripheral artery disease, cognitive function, bone and muscle quality, knee osteoarthritis, carotid intima-media thickness, and blood biomarkers. A comprehensive interview was carried out for demographics, disability and disease history. Annual follow-up visits are ongoing to collect information on incident disability and disease. Results The median age of participants was 66 years (range 60–92 years); median body mass index 21.7 kg/m2, median gait speed 0.67 m/s and 55% self-reported their health status as fair or poor. Conclusions These findings suggest a more frail population in the MILES cohort compared with older adults in USA cohorts. MILES will provide estimates of burden of disease, and disability and risk factors in older adults. Findings will be used to identify potential interventions to prevent disability in this rural Indian population. Geriatr Gerontol Int 2017; 17: 31–40.

OBJECTIVE Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). RESEARCH DESIGN AND METHODS We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ˜6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. RESULTS LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02–2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). CONCLUSIONS LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.

We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6 years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

Poor renal function is associated with increased rates of bone loss and osteoporotic fractures in Caucasian men. The importance of kidney function for skeletal health in African ancestry men, who are a population segment with a high prevalence of chronic kidney disease as well as high peak bone mass, is not well known. We examined the relationship between estimated glomerular filtration rate (eGFR) and rates of bone loss in a large population cohort of otherwise healthy Afro-Caribbean men aged 40 years and older. Dual X-ray absorptiometry of the proximal femur and quantitative computed tomography of the proximal radius and tibia were obtained approximately 6 years apart. We calculated eGFR from serum creatinine that was measured in fasting samples in 1451 men. Impaired kidney function (IKF, eGFR

Low trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD) are related to increased fracture risk, but little is known about the patterns and correlates of Tb and Ct vBMD loss with aging. We examined the rates of change in total, Tb.vBMD, and Ct.vBMD at the radius and tibia, and identified factors associated with vBMD loss among 1569 men of African descent aged 40 years and older. Quantitative computed tomography was used to measure vBMD 6 years apart. The annualized rate of loss in Tb.vBMD was significant at the radius (–0.047%/yr, p = 0.016) but not at the tibia. At the radius, a significant loss of Tb.vBMD was observed in men aged 40 to 49 years that appeared to be attenuated and not statistically significant among older age men. In contrast, the decline in Ct.vBMD was similar at both skeletal sites (–0.254 to –0.264%/yr, p

Genome-wide association studies have identified several loci associated with plasma lipid levels but those common variants together account only for a small proportion of the genetic variance of lipid traits. It has been hypothesized that the remaining heritability may partly be explained by rare variants with strong effect sizes. Here, we have comprehensively investigated the associations of both common and uncommon/rare variants in the lipoprotein lipase (LPL) gene in relation to plasma lipoprotein–lipid levels in African Blacks (ABs). For variant discovery purposes, the entire LPL gene and flanking regions were resequenced in 95 ABs with extreme high-density lipoprotein cholesterol (HDL-C) levels. A total of 308 variants were identified, of which 64 were novel. Selected common tagSNPs and uncommon/rare variants were genotyped in the entire sample (n=788), and 126 QC-passed variants were evaluated for their associations with lipoprotein–lipid levels by using single-site, haplotype and rare variant (SKAT-O) association analyses. We found eight not highly correlated (r2A, rs8176337:G>C, rs74304285:G>A, rs252:delA, rs316:C>A, rs329:A>G, rs12679834:T>C, and rs4921684:C>T) nominally (P

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to

Background Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry. Methods Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. Results Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). Conclusions Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men.Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height.All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p 0.001) when entered in a single model. No ectopic fat measure was associated with CAC.Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.

Black men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001–2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (β-carotene,α-carotene,β-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41–79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serumα- andβ-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.

Objective: While ectopic adiposity is considered a risk factor for many chronic diseases, including cardiovascular disease, the extent to which this association is independent of total adiposity is yet to be established. Vascular calcification, which is associated with greater adiposity, is a subclinical marker of cardiovascular disease that may have varying etiology and clinical implications in different vascular beds. Therefore, our objective was to assess the potential independent associations of total, regional and ectopic adiposity measures with abdominal aorto-iliac calcification (AAC) and coronary artery calcification (CAC). Methods: Detailed health history, clinical exam, dual x-ray absorptiometry and computed tomography (CT) scans were obtained in 798 African ancestry men aged ≥40 years (mean(SD): 62.0(8.6)years) recruited without regard to health status from the Tobago Heart Health Study. Vascular calcification was measured by CT in the abdomen (AAC) and chest (CAC). Calcification was scored using the Agatston method and a score ≥10 was considered to be a prevalent calcification. Severity of calcification was modeled using continuous Agatston score in those with any calcification. Multivariable logistic and linear regression models were used to assess the cross-sectional association of adiposity measures with vascular calcification prevalence and severity. All models were adjusted for age, hypertension, diabetes, dyslipidemia, smoking, alcohol intake and sedentary lifestyle. In addition, models of ectopic adiposity (abdominal visceral adipose tissue, liver attenuation and calf skeletal muscle fat) were adjusted for total body fat. Results: AAC was present in 63% and CAC was present in 29% of men. After adjustment for traditional cardiovascular risk factors, 1SD greater total, trunk, or abdominal subcutaneous adiposity was associated with 1.3-1.5-fold increased odds of AAC (all p Conclusions: Independent of total adiposity, measures of ectopic adiposity were associated with greater AAC, but not CAC, prevalence in African ancestry men. These results highlight potential differences in the adiposity-vascular disease relationship that may vary by ectopic fat depot and vascular bed location. Future vascular disease research should explore potential underlying biologic mechanisms for these findings.

Purpose Traditional disease-free survival (DFS) does not reflect changes in prognosis over time. Conditional DFS accounts for elapsed time since achieving remission and may provide more relevant prognostic information for patients and clinicians. This study aimed to estimate conditional DFS among patients with ovarian cancer and to evaluate the impact of patient characteristics. Patients and Methods Patients were recruited as part of the Hormones and Ovarian Cancer Prediction case-control study and were included in the current study if they had achieved remission after a diagnosis of cancer of the ovary, fallopian tube, or peritoneum (N = 404). Demographic and lifestyle information was collected at enrollment; disease, treatment, and outcome information was abstracted from medical records. DFS was calculated using the Kaplan-Meier method. Conditional DFS estimates were computed using cumulative DFS estimates. Results Median DFS was 2.54 years (range, 0.03-9.96 years) and 3-year DFS was 48.2%. The probability of surviving an additional 3 years without recurrence, conditioned on having already survived 1, 2, 3, 4, and 5 years after remission, was 63.8%, 80.5%, 90.4%, 97.0%, and 97.7%, respectively. Initial differences in 3-year DFS at time of remission between age, stage, histology, and grade groups decreased over time. Conclusion DFS estimates for patients with ovarian cancer improved dramatically over time, in particular among those with poorer initial prognoses. Conditional DFS is a more relevant measure of prognosis for patients with ovarian cancer who have already achieved a period of remission, and time elapsed since remission should be taken into account when making follow-up care decisions.

Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has prognostic value in patients with heart failure (HF). Renal dysfunction is prevalent in HF patients. I-mIBG is excreted by the kidneys, and the effect of renal dysfunction on its myocardial uptake and established prognostic value in HF patients is unknown.The data analysed are from patients with New York Heart Association (NYHA) class II or III HF enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study. Myocardial uptake and retention of I-mIBG were assessed by the early and late heart-to-mediastinal (HM) ratio. Effect of renal dysfunction on the prognostic value of I-mIBG was determined by multivariable-predicted survival analysis stratified by glomerular filtration rate (GFR) and late HM ratio. Cox proportional hazard models were used to determine the predictors of cardiac events (CEs, defined as death, HF progression or life-threatening arrhythmia).Complete data were available on 867 patients. The GFR range was 19-140 ml/min, and 344 (40%) patients had renal dysfunction (GFR60 ml/min). A total of 523 (60%) and 689 (80%) patients had early and late HM ratios below the previously established prognostic cutoff of 1.6. There was no relationship between early or late HM ratios and GFR after controlling for HF severity (NYHA class and norepinephrine levels), indicating a lack of effect of renal dysfunction on the HM ratio. Significant independent predictors of CE were (hazard ratio, P), b-type natriuretic peptide level (1.4,0.001), left ventricular ejection fraction (0.95,0.001), BMI (1.04, 0.002), cardiac glycoside use (1.42, 0.019) and late HM ratio (7.04, 0.008). Neither GFR nor its interaction with late HM ratio was a significant predictor of CE.Renal dysfunction does not affect the HM ratios or the prognostic value of I-mIBG imaging in HF patients.

Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in African ancestry individuals. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among African ancestry men. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD) and hip structural geometry. Among 1,933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD and hip structural geometry were statistically significant risk factors for incident fractures. One Standard deviation change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were 3 times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry and skeletal parameters (hazard ratios ranged 2.72–2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in Caucasian populations. Prior fracture history is a powerful and independent risk factor for incident fractures among African ancestry men and could easily be incorporated into clinical risk evaluation.

Intima-media thickness, adventitial diameter and lumen diameter are indicators of cardiovascular disease risk. The influence of genetic factors on these measures in African ancestry populations is not well defined. Therefore, we estimated heritability and performed genome-wide linkage analysis of carotid ultrasound traits in 7 multigenerational families of African ancestry.A total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative pairs) aged ≥18 years had a common carotid artery ultrasound scan. Statistical analyses were conducted using pedigree-based maximum likelihood methods.Significant covariates included age, sex, body mass index or height and waist, and systolic blood pressure. Residual heritabilities ranged from 0.35 ± 0.10 to 0.64 ± 0.12 (P0.0001). We identified a novel quantitative trait locus for adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm).Further fine mapping of this region may identify specific mutations predisposing to subclinical vascular disease among African ancestry individuals.

Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37–0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.

Bone mineral density (BMD) has been inversely associated with subclinical and clinical cardiovascular disease (CVD) in population studies, but the potential mechanisms underlying this relationship are unclear. To test if there is a genetic basis underlying this association, we determined the phenotypic and genetic correlations between BMD and carotid artery ultrasound measures in families. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to measure BMD in 461 individuals with African ancestry belonging to seven large, multigenerational families (mean family size 66; 3414 total relative pairs). Carotid artery ultrasound was used to measure adventitial diameter (AD) and intima-media thickness (IMT). Phenotypic and genetic correlations between BMD and carotid measures were determined using pedigree-based maximum likelihood methods. We adjusted for potential confounding factors, including age, sex, body weight, height, menopausal status, smoking, alcohol intake, walking for exercise, diabetes, hypertension, serum lipid and lipoprotein levels, inflammation markers, and kidney function. We found statistically significant phenotypic (ρ = −0.19) and genetic (ρG = −0.70) correlations (p

Contains fulltext : 118139.pdf (Publisher’s version ) (Closed access) PURPOSE: The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. METHODS: We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. RESULTS: Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03-1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39-2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12-1.50). For these histological types, consistent dose-response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. CONCLUSIONS: Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

Increased ectopic adipose tissue infiltration in skeletal muscle is associated with insulin resistance and diabetes mellitus. We evaluated whether change in skeletal muscle adiposity predicts subsequent development of hypertension in men of African ancestry, a population sample understudied in previous studies. In the Tobago Health Study, a prospective longitudinal study among men of African ancestry (age range 40–91 years), calf intermuscular adipose tissue, and skeletal muscle attenuation were measured with computed tomography. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg, or receiving antihypertensive medications. Logistic regression was performed with adjustment for age, insulin resistance, baseline and 6-year change in body mass index, baseline and 6-year change in waist circumference, and other potential confounding factors. Among 746 normotensive men at baseline, 321 (43%) developed hypertension during the mean 6.2 years of follow-up. Decreased skeletal muscle attenuation was associated with newly developed hypertension after adjustment for baseline and 6-year change of body mass index (odds ratio [95% confidence interval] per SD, 1.3 [1.0–1.6]) or baseline and 6-year change of waist circumference (odds ratio [95% confidence interval] per SD, 1.3 [1.0–1.6]). No association was observed between increased intermuscular adipose tissue and hypertension. Our novel findings show that decreased muscle attenuation is associated with newly developed hypertension among men of African ancestry, independent of general and central adiposity and insulin resistance. Further studies are needed to adjust for inflammation, visceral and other ectopic adipose tissue depots, and to confirm our findings in other population samples.