Development and feasibility testing of a psychoeducational tool to support the return to work (RTW) of individuals with traumatic brain injury (TBI): The RTW after TBI app.

To document the development and clinician evaluation of a psychoeducational and support tool: the return to work after traumatic brain injury app (RTW after TBI app). Co-design of the app involved the collaboration of traumatic brain injury (TBI) /vocational rehabilitation (VR) expert researchers (n = 4) and lived experience co-designers (individuals with TBI who had previously returned to work; n = 4). Twelve TBI/VR clinician reviewers then evaluated the app. Content analysis of TBI/VR clinician reviewers' interviews revealed four themes: content, usability (functional ease of use), utility (applicability to RTW after TBI) and suggestions for improvements. All clinicians reported that they would use the RTW after TBI app in their clinical practice. Although several aspects were reported to potentially limit the app's appropriateness for some TBI clients, many feasible improvements were suggested to address limitations. These improvements aim to increase the utility of the app with a wider range of clients and extend its use to other settings. Future research should evaluate, in a clinical trial, the efficacy of the RTW after TBI app in supporting individuals with TBI and their vocational providers and optimizing RTW success.

The experience of employers of individuals with traumatic brain injury.

OBJECTIVES: To understand the experience of employers of individuals with traumatic brain injury (TBI) who have received comprehensive vocational rehabilitation (VR), the factors involved in supporting an individual with TBI to return to work (RTW), and the support needs of employers. METHODS: 12 employers completed semi-structured interviews, which were recorded, transcribed, and analysed thematically. RESULTS: Five main themes were identified: challenges and impact on employer, managing employee post-injury changes, looking after employee wellbeing, managing conflicting emotions, and utilizing sources of support. Although employers received support with operational challenges, findings suggest they were not prepared for the emotional journey. While they struggled to support employees through the difficult process of realizing they could no longer perform at their pre-injury level, employers strove to find appropriate roles and ensure wellbeing for their injured employees. Despite employers' endeavours, they felt this process was demoralizing for some employees. CONCLUSIONS: Advising employers on operational as well as emotional support needs of both employees and employers is an ongoing challenge for VR providers. Although unsupportive employers were not well-represented in this sample, the study highlights the challenges faced and strategies used by employers who have a strong personal investment in the successful RTW of their employees.

Investigating feasibility and preliminary efficacy of a simulator-based driving intervention for people with acquired brain injury: A randomised controlled pilot study.

OBJECTIVE: To investigate the feasibility and preliminary efficacy of a driving simulator intervention on driving outcomes following acquired brain injury. DESIGN: Pilot randomised controlled trial. SETTING: Occupational therapy driver assessment and rehabilitation service. SUBJECTS: Individuals post-acquired brain injury aiming to return to driving. INTERVENTION: Eight sessions of simulated driver training over four weeks, in addition to usual care. Control: Usual care only. MAIN MEASURES: Feasibility outcomes: Participant recruitment and retention; data completeness; therapy attendance and fidelity; adverse events. Performance outcomes: on-road driving performance; Simulator Sickness Questionnaire; Brain Injury Driving Self-Awareness Measure and Driving Comfort Scale - Daytime, assessed at baseline and five weeks post-randomisation. RESULTS: Out of 523 individuals screened, 22 (4%) were recruited and randomised, with 20 completing their allocated group (n = 12 Simulator, n = 8 Usual Care). For those who completed training, session attendance was 100% with simulator sickness rated, on average, as mild. Six individuals (50%) in the Simulator group failed the on-road assessment, versus two (25%) in the Usual Care group (P = 0.373). On average, the Simulator group reported a positive change in confidence ratings (M = 5.77, SD = 13.96) compared to the Usual Care group, who reported a negative change (M = -6.97, SD = 8.47), P = 0.034. The Simulator group (M = 0.67, SD = 3.34) demonstrated no significant change in self-awareness relative to the Usual Care group (M = -0.83, SD = 1.83, P = 0.325). CONCLUSIONS: With adjustments to inclusion criteria and recruitment strategies, it may be feasible to deliver the intervention and conduct a larger trial. There is potential benefit of simulator training for improving driver confidence after acquired brain injury.

User experiences and perspectives of a driving simulator intervention for individuals with acquired brain injury: A qualitative study.

Driving a motor vehicle is a common rehabilitation goal following acquired brain injury (ABI). There is increasing interest in the use of driving simulators for driver rehabilitation post-ABI; however, there is still limited research demonstrating efficacy and acceptability. This study sought to examine the user experience of a driving simulator intervention for ABI survivors. Semi-structured interviews were conducted with 14 individuals, including 12 ABI survivors (42% male; Mean age = 53.92 years, SD age = 17.63) who completed the intervention, and 2 occupational therapist driver assessors who facilitated the intervention. Thematic analysis was adopted to analyse interview data. Findings suggest that individual differences (e.g., anxiety, previous experience) influenced participant response to training. The intervention allowed participants to practise various driving skills, re-familiarize themselves with the task of driving, and prepare for return to on-road driving within a safe environment. The intervention was perceived to be useful for enhancing driver self-awareness, autonomy, confidence and patience. Fidelity and simulator sickness were considered limitations of the simulator technology. Subjective accounts of the appropriateness of intervention components are also documented. Overall, the simulator intervention was reported to be a positive experience for participants. Themes emerging from this study can inform future driving simulator interventions for ABI survivors.

Urinary cadmium and timing of menarche and pubertal development in girls.

BACKGROUND: Cadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty. OBJECTIVES: To determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development. METHODS: A cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth. RESULTS: The baseline geometric mean creatinine-adjusted Cd concentration was 0.22 µg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 µg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 µg/L (hazard ratio = 0.42; 95% confidence interval, 0.23-0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline. CONCLUSIONS: These findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls.

The experience of return to work in individuals with traumatic brain injury (TBI): A qualitative study.

Traumatic Brain Injury (TBI) is a leading cause of disability in young people, with return to work (RTW) a major goal of recovery. This qualitative study aimed to understand the RTW experience of individuals with TBI who received comprehensive vocational rehabilitation, and to identify facilitating and limiting factors in the RTW process. Semi-structured interviews were conducted with 15 individuals (mean age = 47.33 years) approximately 4.5 years post-injury, of whom 14 had moderate to severe TBI. Twelve individuals had successfully returned to work. Thematic analysis of transcribed interviews identified three key factors affecting RTW: client, work and rehabilitation factors. Across these factors, 12 themes reported to be critical to the success or failure of the RTW programme were identified. Client themes included social support, cognitive difficulties and motivation, with RTW too early associated with unfavourable outcomes. Work themes included work modifications, employer support and financial incentives. Rehabilitation themes included the RTW programme, the role of the vocational occupational therapist and work preparation. These key factors were reported to have impacted the RTW outcome, comprising three further themes: work satisfaction, future vocational outlook, and quality of life. Consideration of these factors can inform vocational rehabilitation programmes, potentially improving employment outcomes following TBI.

Using Naturalistic Methods to Examine Real-World Driving Behavior in Individuals With TBI Upon Return to Driving: A Pilot Study.

OBJECTIVES: To characterize the real-world driving habits of individuals with traumatic brain injury (TBI) using naturalistic methods and to demonstrate the feasibility of such methods in exploring return to driving after TBI. METHODS: After passing an on-road driving assessment, 8 participants with TBI and 23 matched controls had an in-vehicle device installed to record information regarding their driving patterns (distance, duration, and start/end times) for 90 days. RESULTS: The overall number of trips, distance and duration or percentage of trips during peak hour, above 15 km from home or on freeways/highways did not differ between groups. However, the TBI group drove significantly less at night, and more during the daytime, than controls. Exploratory analyses using geographic information system (GIS) also demonstrated significant within-group heterogeneity for the TBI group in terms of location of travel. CONCLUSIONS: The TBI and control groups were largely comparable in terms of driving exposure, except for when they drove, which may indicate small group differences in driving self-regulatory practices. However, the GIS evidence suggests driving patterns within the TBI group were heterogeneous. These findings provide evidence for the feasibility of employing noninvasive in-car recording devices to explore real-world driving behavior post-TBI.

Self-regulation upon return to driving after traumatic brain injury.

The aim of this study was to explore self-reported driving habits and the factors associated with these within the first three months of return to driving following traumatic brain injury (TBI). Participants included 24 individuals with moderate to severe TBI (post-traumatic amnesia duration M = 33.26, SD = 29.69 days) and 28 healthy age, education, and gender-matched controls who completed an on-road assessment. Driving frequency and avoidance questionnaires were administered to assess premorbid driving, anticipated driving upon resuming, and driving at three months post-assessment. There were no differences between groups for premorbid driving frequency or avoidance. Individuals with TBI anticipated greater reductions in driving frequency, t(29.57) = -3.95, p < .001, and increases in avoidance, U = 171.00, z = -2.69, p < .01. On follow up, significant reductions in frequency, t(48) = -3.03, p < .01, but not avoidance, U = 239.00, z = -1.35, p = .18, were observed. Females were more likely to reduce their driving frequency, rs = -.43, p < .05, while increased anxiety was associated with increased avoidance r = .63, p < .05, and reduced frequency r = -.43, p < .05. It was concluded that individuals with TBI anticipated changes in their driving habits upon return to driving, indicating an expectation for post-injury changes to their driving lifestyle. On follow up, many of these intended changes to driving habits, particularly in relation to driving frequency, were reported by individuals with TBI, suggestive of some strategic self-regulation.

GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer.

Endometrial cancer is the most common gynecological malignancy in the developed world. Although there is evidence of genetic predisposition to the disease, most of the genetic risk remains unexplained. We present the meta-analysis results of four genome-wide association studies (4907 cases and 11 945 controls total) in women of European ancestry. We describe one new locus reaching genome-wide significance (P < 5 × 10 -8) at 6p22.3 (rs1740828; P = 2.29 × 10 -8, OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer.

Self-Awareness and Self-Ratings of On-Road Driving Performance After Traumatic Brain Injury.

OBJECTIVE: To examine self-rated, clinician-rated, and self-awareness of on-road driving performance in individuals with traumatic brain injury (TBI) deemed fit and unfit to resume driving and healthy controls, and to explore their associations with demographic, injury, cognitive, and mood variables. METHODS: Participants included 37 individuals with moderate to severe TBI, and 49 healthy age, sex, and education-matched controls from Australia and Canada. Participants completed an on-road assessment, the Brain Injury Driving Self-Awareness Measure (BIDSAM), and a comprehensive neuropsychological assessment. RESULTS: Awareness scores on the BIDSAM were significantly different between groups, F(2, 83) = 28.44 (P < .001; η = 0.41), with post hoc tests indicating TBI participants who failed the on-road assessment had worse scores compared with those who passed and controls. Poor self-awareness was significantly correlated with reduced psychomotor speed (rs = -0.37; P < .01) and attentional switching (rs = 0.28; P < .01). Worse self-ratings of driving were associated with depression (rs = 0.42; P < .01) and anxiety (rs = 0.38; P < .01). CONCLUSIONS: Individuals with TBI who failed an on-road assessment significantly overestimated their driving ability. Impaired cognitive function was associated with reduced self-awareness of driving. These findings suggest impaired awareness of driving may need to be addressed as part of driver rehabilitation programs.

The development and initial validation of a new tool to measure self-awareness of driving ability after brain injury.

AIM: The aim of this study was to develop and provide initial validation data for a self-awareness of on-road driving ability measure for individuals with brain injury. METHOD: Thirty-nine individuals with Traumatic Brain Injury completed an on-road driving assessment, the Self-Regulation Skills Interview (SRSI) and the newly developed Brain Injury Driving Self-Awareness Measure (BIDSAM). RESULTS: BIDSAM self, clinician and discrepancy scales demonstrated high levels of internal consistency (α = 0.83-0.92). Criterion-related validity was established by demonstrating significantly higher correlations between clinician ratings and on-road performances, rs  = 0.82, P < 0.01, compared to self-ratings, rs  = 0.45, P < 0.05. Discrepancy scores were significantly correlated with the SRSI emergent, rs  = 0.52, P < 0.01, and anticipatory awareness scores, rs  = 0.37, P < 0.05, indicative of convergent validity. CONCLUSIONS: These results provide initial support for the BIDSAM as a reliable and valid measure of self-awareness of on-road driving ability following TBI.

Lifetime body size and estrogen-receptor-positive breast cancer risk in the California Teachers Study cohort.

BACKGROUND: Obesity is a public health epidemic and an important breast cancer risk factor. The relationship between interrelated body measurements is complex and most studies fail to account for this complexity. We identified key aspects of body size which jointly, over the life-course (since adolescence), are associated with estrogen-receptor-positive (ER+) breast cancer risk. METHODS: Among 109,862 women participating in the California Teachers Study cohort, 3844 were diagnosed with invasive ER+ breast cancer between 1997-1998 and December 2011. Based on validated self-reported height and weight at age 18, baseline, and 10-year follow up and waist circumference at 2-year and 10-year follow up, we identified 16 a priori body-size phenotypes. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI). RESULTS: Premenopausal breast cancer was influenced by adolescent, but not adult, body size (HR = 0.51, 95% CI 0.31-0.86 for body mass index (BMI; kg/m2) ≥25 vs <20 at age 18). Among postmenopausal women currently using hormone therapy, only those with the greatest body size had increased breast cancer risk (HR = 1.36, 95% CI 1.13-1.64 for height ≥67 inches and adult BMI ≥25 vs height <67). Among postmenopausal women not currently using hormone therapy, the relationship between body size and risk was complex, with the largest effects of adiposity among short women. Among short women, those with gluteal adiposity (HR = 2.70, 95% CI 1.77-4.10) and those who continued to gain weight throughout adulthood (HR = 2.57, 95% CI 1.60-4.12) were at greatest risk, whereas those who had been overweight/obese since adolescence were not at increased risk (HR = 1.33, 95% CI 0.84-2.10). Height was associated with a small increased risk, with borderline statistical significance. CONCLUSIONS: Considering absolute body mass in adolescence and at two points in adulthood, dynamic changes in adiposity over time, and body fat distribution, we identified obesity phenotypes associated with ER+ breast cancer risk. Our approach more clearly identifies specific risk groups than do analyses that evaluate similar measures separately. These findings may aid in improving risk prediction models and developing targeted interventions, and may clarify inconsistent findings across studies.

Body size over the life-course and the risk of endometrial cancer: the California Teachers Study.

PURPOSE: Obesity is a public health epidemic and a major risk factor for endometrial cancer. Here, we identify key aspects of body size which jointly, over the life-course (since adolescence), are associated with endometrial cancer risk. METHODS: Among 88,142 participants in the California Teachers Study, 887 were diagnosed with invasive type 1 endometrial cancer between 1997-1998 and 2012. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI) for endometrial cancer associated with life-course body size phenotypes, which incorporated validated measures. RESULTS: Among women currently using hormone therapy, endometrial cancer risk was only associated with height (HR 1.78, 95% CI 1.32-2.40 for ≥67 vs. <67 inches). Among women not using hormone therapy, tall women who were overweight/obese in adolescence (HR 4.33, 95% CI 2.51-7.46) or who became overweight/obese as adults (HR 4.74, 95% CI 2.70-8.32) were at greatest risk. CONCLUSIONS: Considering absolute body mass, changes in adiposity over time, and body fat distribution together, instead of each measure alone, we identified lifetime obesity phenotypes associated with endometrial cancer risk. These results more clearly define specific risk groups, and may explain inconsistent findings across studies, improve risk prediction models, and aid in developing targeted interventions for endometrial cancer.

Predictors of the On-Road Driving Assessment After Traumatic Brain Injury: Comparing Cognitive Tests, Injury Factors, and Demographics.

OBJECTIVES: (1) To examine the relations between performance on cognitive tests and on-road driving assessment in a sample of persons with traumatic brain injury (TBI). (2) To compare cognitive predictors of the on-road assessment with demographic and injury-related predictors. PARTICIPANTS: Ninety-nine people with mild-severe TBI who completed an on-road driving assessment in an Australian rehabilitation setting. DESIGN: Retrospective case series. MAIN MEASURES: Wechsler Test of Adult Reading or National Adult Reading Test-Revised; 4 subtests from the Wechsler Adult Intelligence Scale-III; Rey Auditory Verbal Leaning Test; Rey Complex Figure Test; Trail Making Test; demographic factors (age, sex, years licensed); and injury-related factors (duration of posttraumatic amnesia; time postinjury). RESULTS: Participants who failed the driving assessment did worse on measures of attention, visual memory, and executive processing; however, cognitive tests were weak correlates (r values <0.3) and poor predictors of the driving assessment. Posttraumatic amnesia duration mediated by time postinjury was the strongest predictor of the driving assessment-that is, participants with more severe TBIs had later driving assessments and were more likely to fail. CONCLUSION: Cognitive tests are not reliable predictors of the on-road driving assessment outcome. Traumatic brain injury severity may be a better predictor of on-road driving; however, further research is needed to identify the best predictors of driving behavior after TBI.

Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium.

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥ 35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥ 45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥ 10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.

Dietary patterns and endometrial cancer risk in the California Teachers Study cohort.

PURPOSE: Information on the role of dietary patterns and endometrial cancer risk is limited. We investigated whether dietary patterns are associated with endometrial cancer risk among women in the California Teachers Study cohort. METHODS: Among 75,093 eligible women, 937 developed invasive endometrial cancer between 1995 and 2011. Multivariate Cox regression was performed to estimate relative risks (RR) and 95% confidence intervals (CI) associated with five dietary patterns identified by principal components factor analysis: "plant-based," "high protein/high fat," "high carbohydrates," "ethnic," and "salad and wine." RESULTS: These dietary patterns were not associated with endometrial cancer risk overall (RR = 0.91, 95% CI: 0.72, 1.15 for the highest vs. lowest quintile of the "plant-based" dietary pattern) or by menopausal status and hormone therapy use. CONCLUSIONS: Dietary patterns do not seem to be associated with endometrial cancer risk.

Risk factors for endometrial cancer in black and white women: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2).

PURPOSE: Endometrial cancer (EC) is the most common gynecologic cancer in the USA. Over the last decade, the incidence rate has been increasing, with a larger increase among blacks. The aim of this study was to compare risk factors for EC in black and white women. METHODS: Data from seven cohort and four case-control studies were pooled. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals for each risk factor in blacks and whites separately. RESULTS: Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). BMI ≥ 30 was associated with an approximate threefold increase in risk of EC in both black and white women (ORblack 2.93, 95 % CI 2.11, 4.07 and ORwhite 2.99, 95 % CI 2.74, 3.26). Diabetes was associated with a 30-40 % increase in risk among both groups. Increasing parity was associated with decreasing risk of EC in blacks and whites (p value = 0.02 and <0.001, respectively). Current and former smoking was associated with decreased risk of EC among all women. Both black and white women who used oral contraceptives for 10 +years were also at reduced risk of EC (OR 0.49, 95 % CI 0.27, 0.88 and OR 0.69, 95 % CI 0.58, 0.83, respectively). Previous history of hypertension was not associated with EC risk in either group. CONCLUSIONS: The major known risk factors for EC exert similar effects on black and white women. Differences in the incidence rates between the two populations may be due to differences in the prevalence of risk factors.

Predictors of on-road driver performance following traumatic brain injury.

OBJECTIVE: To examine assessment outcomes and factors associated with passing an occupational therapy (OT) on-road driver assessment after traumatic brain injury (TBI). DESIGN: Retrospective analysis of outcomes of on-road driver assessment completed by persons with TBI over an 8-year period. SETTING: Inpatient and outpatient rehabilitation hospital. PARTICIPANTS: A consecutive sample of individuals (N=207) with mild to severe TBI who completed an on-road driver assessment and were assessed at least 3 months postinjury. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Outcome of on-road driver assessment. RESULTS: Of the drivers with TBI, 66% (n=137) passed the initial on-road driver assessment (pass group), whereas 34% (n=70) required on-road driver rehabilitation and/or ≥1 on-road assessment (rehabilitation group). After driver rehabilitation, only 3 participants of the group did not resume driving. Participants who were men, had shorter posttraumatic amnesia (PTA) duration, had no physical and/or visual impairment, and had faster reaction times were significantly more likely to be in the pass group. In combination, these variables correctly classified 87.6% of the pass group and 71.2% of the rehabilitation group. CONCLUSIONS: PTA duration proved to be a better predictor of driver assessment outcome than Glasgow Coma Scale score. In combination with the presence of physical/visual impairment and slowed reaction times, PTA could assist clinicians to determine referral criteria for OT driver assessment. On-road driver rehabilitation followed by on-road reassessment were associated with a high probability of return to driving after TBI.

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

Genome-wide association study of endometrial cancer in E2C2.

Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility.