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BackgroundAccumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.MethodsUsing LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.ResultsGenetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.ConclusionsUsing cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.ImpactOur research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

Abstract: Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses by stratified by subtype. We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10−7). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.

BackgroundPrevious gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.MethodsAnalyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.ResultsNoteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.ConclusionsOverall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

BackgroundCoffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.MethodsWe used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator.ResultsFor all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases.ConclusionsWe found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

Context Medical school curricula remain one of the key levers in increasing the future supply of rural doctors. Data from Australia and overseas have suggested exposure to rural practice via rural placements during basic medical training is positively associated with graduates becoming rural doctors. However, previous studies have suffered from serious methodological limitations. Objectives This study sought to determine whether rural clinical placements are associated with a higher proportion of graduating students planning rural careers and to explore associations with timing, duration and location of placements. Methods Data were obtained from the Medical Schools Outcomes Database and Longitudinal Tracking Project, which is a longitudinal study with a high response rate that prospectively collects data, including practice location intention, from all Australian medical schools. Using logistic regression analysis, the association between placements and rural career intention was assessed, controlling for a number of demographic and contextual variables. Results The association between rural/remote placements later in the programme and rural practice intention was strongly positive whether viewed as simple occurrence or as duration, in contrast to later urban placements, which were strongly negative. A longer duration of placement enhanced the associations reported. Non-metropolitan medical schools were also associated with higher odds of intention to take up rural practice. However, the association with rural placements was overshadowed by the strong positive associations with rural background of students and their stated intention to become a rural doctor at the start of their studies. Conclusions Exposure to rural practice during basic medical training, and the location and curriculum focus of a medical school are confirmed as factors that are positively associated with students' intention to become rural doctors after graduation. However, rural origin and the early intentions at the start of their medical training are better predictors of expressed intention to take up rural practice than rural clinical placements. [ABSTRACT FROM AUTHOR]

The article presents a study of characterizing associations between psychosocial and work organizational risk factors and upper-extremity musculoskeletal symptoms and disorders. It discusses the association of musculoskeletal disorder (MSD) risk with multiple factors including personal characteristics, psychosocial stress, and workplace organization factors. Details of the assessment of musculoskeletal outcomes, and data analysis and statistical methods used in the study are presented.

Background: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods: We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results: In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56–0.75, p = 3.32 × 10−10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31–0.62, p = 9.91 × 10−8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46–0.71, p = 1.88 × 10−8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60–0.84, p = 1.64 × 10−7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions: BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Objective Recent efforts to redress the deficit of rural medical practitioners have considered the problem of recruitment and retention of rural doctors as one of influencing individuals' career choices. Exposure to rural medical environments during basic medical training is one long-standing example of an initiative aimed in this direction and there is some evidence that it is effective. This study sought to determine whether or not various domains of personality are related to medical students' attitude to practising as rural doctors after graduation. Design The sample comprised 914 students commencing medical studies in Australian universities. They were recruited as part of the Medical Schools Outcomes Database project and indicated intended location of future medical practice. Setting Seven Australian basic medical training programs. Main outcome measures All students completed the NEO five-factor index ( NEO-FFI) and Adjective Checklist ( ACL) personality instruments. Results A preference for a rural practice location was associated with a combination of six domains of personality. The probability of rural preference was greater with higher scores on openness to experience, agreeableness and self-confidence but lower with higher scores on extraversion, autonomy and intraception. Taken together these six domains of personality provide useful although imperfect discrimination between students with a rural versus urban location preference. After controlling for student age the associations with extraversion and agreeableness failed to reach statistical significance. Conclusions While personality does not fully explain medical students' attitude towards practicing as a rural doctor, the data suggest it is an important factor and that some individuals may be better suited to a rural medical career than others. Considering personality along with other characteristics of the individual might allow targeted 'marketing' of rural practice. [ABSTRACT FROM AUTHOR]

Context: Little is known about the role of personality and related constructs in general practitioners' (GPs) choices of geographic location of medical practice. There is however some theory suggesting a role for personality in career decision making and some limited empirical evidence that this applies in medical career decisions. Purpose: The aim of this study is to gain insight into whether personality plays a role in GPs' decisions to work in rural areas and the length of time that they intend to remain as a rural practitioner. Method: Samples of rural (n = 372) and urban (n = 100) GPs from New South Wales (Australia) completed the Neuroticism, Extraversion, Openness - Five Factor Inventory (NEO-FFI) and Adjective Checklist personality instruments and answered questions about demographics and rural upbringing. Findings: Rural GPs scored, on average, more highly than urban GPs with respect to conscientiousness and agreeableness but lower on openness, which can also be taken to mean a more 'down-to-earth' personality. Personality together with age, gender, experience as a GP, time in current location and rural childhood yield an area under the receiver operating characteristic curve of 0.81 in discriminating rural from urban GPs. Among rural GPs openness (P = 0.007) was positively correlated with intended longevity as a rural doctor as was nurturing (P = 0.06). Conclusions: Personality appears to play some role both in discriminating rural from urban GPs and in how long existing rural GPs intend to remain as rural GPs. Consideration of personality might assist in selection of individuals who will better fit the professional and social environment of rural life. [ABSTRACT FROM AUTHOR]

Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function. Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS). Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates. Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold. Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators. [ABSTRACT FROM AUTHOR]

Background.: We investigated whether prior hospitalization was a risk factor for heart attacks among older adults in the survey on Assets and Health Dynamics among the Oldest Old. Methods. Baseline (1993–1994) interview data were linked to 1993–2005 Medicare claims for 5,511 self-respondents aged 70 years and older and not enrolled in managed Medicare. Primary hospital International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) 410.xx discharge codes identified postbaseline hospitalizations for acute myocardial infarctions (AMIs). Participants were censored at death or postbaseline managed Medicare enrollment. Traditional risk factors and other covariates were included. Recent postbaseline non-AMI hospitalizations (ie, prior hospitalizations) were indicated by a time-dependent marker, and sensitivity analyses identified their peak effect. Results. T he total number of person-years of surveillance was 44,740 with a mean of 8.1 (median = 9.1) per person. Overall, 483 participants (8.8%) suffered postbaseline heart attacks, with 423 participants (7.7%) having their first-ever AMI. As expected, significant traditional risk factors were sex (men); race (whites); marital status (never being married); education (noncollege); geography (living in the South); and reporting a baseline history of angina, arthritis, diabetes, and heart disease. Risk factors were similar for both any postbaseline and first-ever postbaseline AMI analyses. The time-dependent recent non-AMI hospitalization marker did not alter the effects of the traditional risk factors but increased AMI risk by 366% (adjusted hazards ratio = 4.66, p < .0001). Discussion. Our results suggest that some small percentage (<3%) of heart attacks among older adults might be prevented if effective short-term postdischarge planning and monitoring interventions were developed and implemented. [ABSTRACT FROM PUBLISHER]

The article presents a research regarding the health condition of the Chinook salmon residing in the Lake Michigan. It looks on the effects of the fish pathogens, to the health condition of these salmon and cites how the researchers exerted their efforts in assessing the condition of these fishes by creating an approach in order to assess the total health condition of the fishes while interacting with the said fish pathogens. In addition, the newly-hatched fishes' health and their survivability are also determined.

Methods. Baseline (1993-1994) interview data were linked to Medicare claims for 1993-2005. Participants were 5,511 self-respondents aged 70 years and older and not in managed Medicare. ICD9-CM 820.xx (International Classification of Diseases, 9th Edition, Clinical Modification) codes identified hip fracture. Participants were censored at death or enrollment into managed Medicare. Static risk factors included sociodemographic, socioeconomic, place of residence, health behavior, disease history, and functional and cognitive status measures. A time-dependent marker reflecting post- baseline hospitalizations was included. Results. A total of 495 (8.9%) participants suffered a postbaseline hip fracture. In the Static proportional hazards model, the greatest risks involved age (adjusted hazard ratios [AHRs] of 2.01, 2.82, and 4.91 for 75-79, 80-84, and ?85 year age groups vs those aged 70-74 years; p values <.001), sex (AHR = 0.45 for men vs women; p <.001), race (AHRs of 0.37 and 0.46 for African Americans and Hispanics vs whites; p values <.001 and <.01), body mass (AHRs of 0.40, 0.77, and 1.73 for obese, overweight, and underweight vs normal weight; p values <.001, <.05, and <.01), smoking status (AHRs = 1.49 and 1.52 for current and former smokers vs nonsmokers; p values <.05 and <.001), and diabetes (AHR = 1.99; p < .001). The time-dependent recent hospitalization marker did not alter the static model effect estimates, but it did substantially increase the risk of hip fracture (AHR = 2.51; p < .001). Conclusions. Enhanced discharge planning and home care for non-hip fracture hospitalizations could reduce subsequent hip fracture rates [ABSTRACT FROM AUTHOR]

There is controversy about whether psychological factors (anxiety and depression) increase health care seeking by patients with irritable bowel syndrome (IBS). We investigated whether psychological factors increase health care seeking by patients with IBS and the effects of extragastrointestinal (extra-GI) symptoms. We performed a population-based prospective study of health care use over a 12-year period in Sweden. From 2002 through 2006, 1244 subjects were selected randomly for an examination by a gastroenterologist and to complete questionnaires, including the Rome II modular questionnaire. Psychological factors were measured with the valid Hospital Anxiety and Depression scale and extra-GI symptoms were measured with a symptom checklist. Responses from 1159 subjects (57% female; mean age, 48.65 y) were matched with health records in 2016 (164 were classified as having IBS based on Rome II criteria). The overall association between depression or anxiety and health care use varied in subjects with and without IBS at baseline. The presence of extra-GI symptoms strengthened the relationship between anxiety and depression and prospective psychiatric visits for subjects with IBS and without IBS (incidence rate ratio, 1.14–1.26). Extra-GI symptoms did not alter the association of anxiety or depression with use of GI or extra-GI health care. In a population-based study in Sweden, we found that individuals with high baseline anxiety or depression were more likely to seek psychiatric health care, but not GI or extra-GI health care, in the presence of extra-GI symptoms at baseline. Patients with IBS might benefit from more thorough assessments that examine extra-GI and psychological symptoms, to reduce health care utilization. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Wehypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing. METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n51,151, 21-79 years, response rate [rr] 5 90%), 1989 (n 5 1,097, 22-80 years, rr 5 87%), 1995 (n 5 1,139, 20-85 years, rr 5 76%), and 2011 (n 5 1,175, 20-93 years, rr 5 63%). RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60-4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42-1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50-2.73). DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined. [ABSTRACT FROM AUTHOR]

Abstract: Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61years (SD=12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators. [Copyright &y& Elsevier]