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Background: Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP).Methods: This Canadian population-based case-control study (2001-2012) included 854 invasive cases/2139 controls aged ⩾40 years who were parous and had information on COC use. We estimated odds ratios (aORs) and 95% confidence intervals (CI) adjusted for study site, age, parity, breastfeeding, age at FFTP, familial breast/ovarian cancer, tubal ligation, and body mass.Results: Among parous women, per year of COC use exclusively before the FFTP was associated with a 9% risk reduction (95% CI=0.86-0.96). Results were similar for high-grade serous and endometrioid/clear cell EOC. In contrast, per year of use exclusively after the FFTP was not associated with risk (aOR=0.98, 95% CI=0.95-1.02).Conclusions: Combined oral contraceptive use before the FFTP may provide a risk reduction that remains for many years, informing possible prevention strategies. [ABSTRACT FROM AUTHOR]

Background: The risk for epithelial ovarian cancer associated with the consumption of caffeinated beverages (tea, coffee, and soft drinks) and green tea is inconclusive. However, few studies have investigated the type of caffeinated beverage or the type of tea.Objective: We assessed consumption of tea (black/caffeinated tea and green tea separately), coffee, and caffeinated soft drinks, as well as level of consumption, and the risk for epithelial ovarian cancer and its histotypes.Study Design: This study was conducted within a population-based case-control study in Alberta and British Columbia, Canada from 2001 to 2012. After restricting to cases of epithelial invasive cancers and controls aged 40-79 years who completed an interview that included coffee, soft drink, and tea consumption (ascertained starting in 2005 in British Columbia and 2008 in Alberta), there were a total of 524 cases and 1587 controls. Those that did not meet the threshold for beverage consumption (at least once per month for 6 months or more) were classified as non-drinkers. Adult lifetime cumulative consumption (cup-years=cups/day*years) was calculated. Unconditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to describe the association between the relevant drink consumption and risk.Results: No excess risk was seen for coffee or caffeinated soft drinks. Similarly, any tea consumption was not associated with risk, but when stratified by the type of tea, there was an increase in risk in black tea only drinkers (aOR=1.56; 95% CI:1.07-2.28 for >40 cup-years), but no excess risk for the exclusive green tea drinkers. Similar findings were observed for post-menopausal women. The association for black tea only consumption was mainly seen in the endometrioid histotype (aOR=3.19; 95% CI: 1.32-7.69).Conclusion: Black tea consumption may be associated with an increased risk epithelial ovarian carcinoma. The excess risk is seen only in the endometrioid histotype but not in serous or clear cell. Further studies are required to confirm these findings and identify the constituents in black tea that may increase the risk. [ABSTRACT FROM AUTHOR]

Background: Research suggests pets foster affection, connection, and physical activity, yet has failed to address the challenges people diagnosed with cancer face in caring for their pets. The objective of this study was to better understand how pets serve as emotional buffers and/or stressors for people diagnosed with breast cancer, and how their ability to meet their pet's needs affects their well-being. Methods: A cross-section study of people diagnosed with breast cancer in the United States was conducted. Adults diagnosed with stages 0 (in situ) -IV breast cancer and currently the primary guardian of at least one dog or cat and owned the animal(s) for at least 6 months, were recruited for the study. A total of 211 responses, obtained between July – November 2022 were analyzed. The survey included questions about participants' demographics; attachment to their pets; physical, emotional, and functional well-being; social support received from their pet; and 'pet parenting' concerns. Descriptive statistics were calculated to describe participants' demographics. Multiple regression analyses were conducted to determine predictors of pet attachment, well-being, support from pet, and 'pet parenting' concerns. Results: People diagnosed with breast cancer derive substantial support from their pets (80% feel their pet makes them feel loved, needed, and offers a positive presence in the home), yet only 50% of participants feel this relationship is supported by their medical team. Controlling for owner demographics, heightened levels of pet-related guilt and concerns, along with lower perceived support from their pet, are all significant predictors of a lower quality of life. Conclusions: Findings highlight the benefits pets offer people diagnosed with breast cancer, yet also the distress they feel in trying to meet their pet's needs. Assessment conversations about pet ownership, including pet-related support systems, are needed to validate people's concerns and support the identification and development of pet support teams. Medical team facilitated discussions about pet care needs is suggested to demonstrate support for the pet-parent bond and help normalize feelings of guilt related to challenges in meeting their pet's needs. These discussions could be aided through the development of research-driven intervention strategies and online, freely accessible targeted tools. [ABSTRACT FROM AUTHOR]

Well-constructed epidemiologic studies provide information about environmental risks and inform interventions and public health policies. Using focus groups, this pilot project examined the attitudes, beliefs, and concerns of rural-dwelling adults toward participating in a longitudinal cohort study. Focus group participants who were 40 years or older, residents in the Grants Mining District, and had no previous diagnosis of diabetes (except gestational diabetes) were recruited from a local physician's office in the Grants Mining District. Participants provided insight into local health concerns, willingness to participate in long-term research and to provide biological specimens, and consent form expectations. For this population, the uranium mining legacy in the Grants Mining District is a contextual factor that can be addressed via community engagement and in the study design to minimize misinterpretation or bias and to maximize the ability to detect causal risk factors for health outcomes. [ABSTRACT FROM AUTHOR]

Objective Meta-analyses report a null association between recent alcohol consumption and ovarian cancer risk. However, because few studies investigated different types of alcohol over adult ages, we investigated adult lifetime and type (beer, wine, spirits) of consumption and risk. Methods Consumption after age 20 years was ascertained in 1144 invasive epithelial ovarian cancer cases and 2513 controls in a population-based case–control study (Alberta and British Columbia, Canada, 2001–2012). Non-drinkers consumed any types of alcohol < 12 times per year on average. Logistic regression was use to estimate adjusted odds ratios [aOR] and 95% confidence intervals [CIs]. Results Wine consumption was associated with a risk reduction (aOR = 0.67, 95% CI: 0.50–0.88) relative to non-drinkers, but not beer (aOR = 1.06, 95% CI: 0.71–1.58) or spirits (aOR = 0.98, 95% CI: 0.69–1.39). The reduced risk was stronger for exclusive red wine drinkers (aOR = 0.44, 95% CI: 0.19–0.92) than white wine drinkers (aOR = 0.79, 95% CI: 0.46–1.34), although most women drank both types of wine. Risk decreased with increasing cumulative consumption of any wine (P-trend < 0.05) and was evident for the serous histotype. Wine consumption initiated prior to age 50 was associated with a risk reduction (e.g., at 40–49 years, aOR = 0.58, 95% CI: 0.42–0.78), but not drinking initiated after 50 years of age. For any type, level, or age at initiation of alcohol consumption, we found no increased risks. Conclusions For the moderate consumption in this study, higher levels of wine consumption were generally associated with risk reductions; reductions may be stronger for red wine. Our results suggest that alcohol consumption that is guideline concordant will not increase epithelial ovarian cancer risk. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the inter-method reliability of the Ovarian Cancer in Alberta (OVAL) survey developed to estimate adult vitamin D exposure from sun and diet for every tenth year, against the longer Geraldton Skin Cancer Prevention Survey (the assumed ‘gold standard’). We also estimated total vitamin D exposure using the OVAL survey.DesignA randomized crossover design to assess the inter-method reliability of sun exposure (OVAL v. Geraldton survey), using intra-class correlation and estimated total vitamin D exposure from sun and diet.SettingCalgary, Alberta, Canada.SubjectsRandomly selected women (n 90) aged 40–79 years.ResultsThe average lifetime sun exposure of 13 913 h (average 411 h/year) from the Geraldton survey was not significantly different from the 13 034 h (average 385 h/year) from the OVAL survey for periods with sufficient UV radiation to stimulate vitamin D production. The intra-class correlation coefficient for average lifetime sun exposure was 0·77 (95 % CI 0·69, 0·86); the annual average was 0·60 (95 % CI 0·47, 0·74). Estimated vitamin D from diet and supplements increased with age.ConclusionsOur OVAL survey reliably estimated adult sun exposure relative to the Geraldton survey, suggesting that assessing sun exposure every tenth year is a reliable and efficient method for estimating sun contributions to lifetime vitamin D exposure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients. Methods: This population-based case–control study included 519 EC cases and 1015 age-matched controls and took place in Alberta, Canada between 2002 and 2006. Information about risk factors, including family history of cancer in first and second degree relatives, was ascertained via in-person interviews. Microsatellite instability (MSI) status of tumor tissue was assessed to determine involvement of DNA mismatch repair (MMR) genes. Results: A first or second degree family history of uterine cancer was modestly associated with the risk for overall EC [odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9, 1.9], and the risks were similar for MSI+cancer (OR=1.5, 95%CI=0.7, 3.3) and MSI− cancer (OR=1.3, 95%CI=0.8, 2.4). Although consistent, these associations were modest and not significant. In contrast, the risk for MSI+cancer was elevated with a reported family history of colorectal cancer (OR=1.4, 95%CI=1.0, 2.2), but not for MSI− cancer. Conclusions: A family history of uterine cancer may be modestly associated with EC risk in non-LS patients regardless of MSI status, suggesting that risk was not related to inherited defects in the MMR gene pathway. These results provide preliminary support for an EC-specific genetic syndrome. [Copyright &y& Elsevier]

OBJECTIVE: To describe the association between intima-media thickness (IMT) and metabolic syndrome (MetS) and to examine if the addition of IMT to a traditional MetS definition adds value to the assessment of predicted cardiovascular disease (CVD) risk in a large multiethnic population. PARTICIPANTS AND METHODS: In this cross-sectional study, carotid IMT was measured in 2268 men and women as part of a wellness physical examination between August 1, 2000, and October 1, 2001. The wellness examination included a fasting lipid panel, physical examination, and medical history. Mean IMT was described by sex, ethnicity, and the MetS. Predicted risk for CVD was determined with IMT as a component of the diagnostic criteria for MetS. RESULTS: intima-media thickness increased with each additional component of the MetS, Increasing from 0.516 mm for 0 components to 0.688 mm for 4 or more components (P<.001). in each ethnic group (non-Hispanic whites, blacks, Hispanics, and Asians), those with the MetS had higher mean IMT (increased by 0.084 mm to 0.134 mm) than those without MetS. The addition of 1MT as a "new" component in the diagnosis of MetS allowed us to identify 78 (34%) participants who were not previously diagnosed as having MetS but who had a high 10-year estimated risk of MetS as measured by the Framingham risk score (11.67%). CONCLUSION: The addition of IMT to the traditional criteria for the diagnosis of the MetS may help Identify individuals who otherwise would not have been identified to be at high risk of CVD. [ABSTRACT FROM AUTHOR]

When more than one characteristic of an exposure is under study, it is easy to misinterpret the results of a logistic regression analysis that incorporates terms for each characteristic. For example, in a study of the risk of endometrial cancer in relation to the duration and the recency of use of estrogen replacement therapy (ERT), simultaneously including terms for duration and recency of exposure to ERT in a logistic model may leave the mistaken impression that it is possible to adjust for recency when a given duration of ERT use is compared with no use. In this article, the authors show why such an adjusted comparison is impossible, and they discuss several pitfalls in the interpretation of logistic regression coefficients when two or more characteristics of exposure are under study. They also suggest a method for avoiding these pitfalls. Am J Epidemiol 1999; 149:984–92. [ABSTRACT FROM PUBLISHER]

Background and Aims: We examined birth cohort and calendar period trends in hepatocellular carcinoma (HCC) incidence in Canada (1976–2000). We also projected HCC incidence rates through 2015. Patients and methods: Data were obtained from the Canadian Cancer Registry on all cases of HCC diagnosed among persons aged 20 years and older in Canada from 1976 to 2000 and was used to describe trends in HCC incidence rates. Results: We found that age-adjusted HCC incidence rates increased faster in males compared with females, 3.4% per year [95% confidence interval (CI): 3.0–3.8%] vs 2.2% per year (95% CI: 1.5–2.8%). An increasing birth cohort trend accelerated among males around the 1940 birth cohort and decelerated among females around the 1935 birth cohort. For calendar period trends, the increasing HCC risk was relatively constant over time among males whereas there was an acceleration in HCC risk around 1988 among females. Age-adjusted HCC incidence rates were projected to increase 73% in males and 28% in females from 1996 to 2015. Conclusions: Our results suggest that HCC incidence rates will continue to increase in Canada during the next decade as persons born in more recent birth cohorts, who face a relatively greater risk for HCC, age. [ABSTRACT FROM AUTHOR]

The effects of gender on selected treatment variables of substance-abusing persons were investigated with the long-term goal of designing gender-appropriate programs for the treatment of addiction. A population of 120 male and female substance abusers was drawn from two urban outpatient drug treatment centers and one HIV outpatient counseling center. Participants were given questionnaires to measure the following variables: trait anxiety, depression, coping style, and level of differentiation of self. Results demonstrated significant gender differences in differentiation of self (p < .005) and coping styles (p < .02) but no significant differences in anxiety or depression. [ABSTRACT FROM AUTHOR]

Telomere length is linked to age-associated diseases, with shorter telomeres in blood associated with an increased probability of mortality from infection or heart disease. Little is known about how human telomere length is regulated despite convincing data from twins that telomere length is largely heritable, uniform in various tissues during development until birth and variable between individuals. As sperm cells show increasing telomere length with age, we investigated whether age of fathers at conception correlated with telomere length of their offspring. Telomere length in blood from 125 random subjects was shown to be positively associated with paternal age (+22 bp yr−1, 95% confidence interval 5.2–38.3,P = 0.010), and paternal age was calculated to affect telomere length by up to 20% of average telomere length per generation. Males lose telomeric sequence faster than females (31 bp yr−1, 17.6–43.8,P < 0.0001 vs. 14 bp yr−1, 3.5–24.8,P < 0.01) and the rate of telomere loss slows throughout the human lifespan. These data indicate that paternal age plays a role in the vertical transmission of telomere length and may contribute significantly to the variability of telomere length seen in the human population, particularly if effects are cumulative through generations. [ABSTRACT FROM AUTHOR]

PURPOSE: Information obtained by telephone interviews and in-person interviews is generally considered comparable, but it is unclear if extensive memory aids can be used effectively with telephone interviews. We compared a telephone interview to an in-person interview using the same questionnaire and memory aids in both.METHODS: A convenience sample of 103 women, aged 25 to 69 years, completed a telephone interview and at least four weeks later, completed an in-person interview. Memory aids included a life events calendar, cue lists, and worksheets.RESULTS: Agreement values, measured by kappa/weighted kappa, were as follows: parity (1.00), age at menarche (0.76), menopausal status (0.95), a history of reproductive organ surgery (0.98) or tubal ligation (0.91), self-reported infertility (0.76), and a first degree family history of breast/ovarian cancer (0.90). Agreement values for duration variables, measured by the intraclass correlation, were as follows: lactation (0.96), oral contraceptive use (0.98), any hormone replacement therapy (0.98), exclusive estrogen and progesterone therapy (0.83), and exclusive estrogen therapy (0.99).CONCLUSIONS: The good to excellent level of agreement found in this study indicates that telephone administration of our questionnaire with extensive memory aids is a reliable method of obtaining detailed exposure information relative to in-person interviews. [Copyright &y& Elsevier]

Drug abuse and delinquent behavior in adolescents have been closely linked in the literature. It is possible that these links are not causal, but rather covariates of the common factor of family. This paper seeks to examine the behaviors of addiction and delinquency within the framework of family systems theory. [ABSTRACT FROM AUTHOR]

Objectives. New evidence linking lack of circumcision with sexually transmitted human immunodeficiency virus revives concerns about circumcision and other sexually transmitted diseases. This study was undertaken to assess the relationship between circumcision and syphilis, gonorrhea, chlamydial infection, genital and exophytic genital warts. Methods. A cross-sectional study of 2776 heterosexual men attending a sexually transmitted disease clinic in 1988 was used to investigate the relationship between circumcision and sexually transmitted diseases. Subjects with specific sexually transmitted diseases and those without such diseases were compared after adjustment for age, race, zip code of residence, other sexually transmitted diseases, and number of sexual partners. Results. A positive relationship was observed between uncircumcised status and both syphilis and gonorrhea. A negative relationship was found between warts and lack of circumcision. No apparent relationship was noted between uncircumcised status and genital herpes, chlamydial infection, or nongonococcal urethritis. Conclusions. Uncircumcised men were more likely than circumcised men to have syphilis and gonorrhea and were less likely to have visible warts. [ABSTRACT FROM AUTHOR]

Compares selected characteristics of women with and without augmentation mammaplasty to identify differences between these two groups of women. Objective; Design and study participants; Main outcome measure; Results; Conclusion.

Cytoreductive surgery and chemotherapy are cornerstones of ovarian cancer treatment, yet disease recurrence remains a significant clinical issue. Surgery can release cancer cells into the circulation, suppress anti-tumor immunity, and induce inflammatory responses that support the growth of residual disease. Intervention within the peri-operative window is an under-explored opportunity to mitigate these consequences of surgery and influence the course of metastatic disease to improve patient outcomes. One drug associated with improved survival in cancer patients is ketorolac. Ketorolac is a chiral molecule administered as a 1:1 racemic mixture of the S- and R-enantiomers. The S-enantiomer is considered the active component for its FDA indication in pain management with selective activity against cyclooxygenase (COX) enzymes. The R-enantiomer has a previously unrecognized activity as an inhibitor of Rac1 (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42) GTPases. Therefore, ketorolac differs from other non-steroidal anti-inflammatory drugs (NSAIDs) by functioning as two distinct pharmacologic entities due to the independent actions of each enantiomer. In this review, we summarize evidence supporting the benefits of ketorolac administration for ovarian cancer patients. We also discuss how simultaneous inhibition of these two distinct classes of targets, COX enzymes and Rac1/Cdc42, by S-ketorolac and R-ketorolac respectively, could each contribute to anti-cancer activity. [ABSTRACT FROM AUTHOR]

Inhibition of the MAPK pathway by MEK inhibitors (MEKi) is currently a therapeutic standard in several cancer types, including ovarian low-grade serous carcinoma (LGSC). A common MAPK pathway alteration in tubo-ovarian high-grade serous carcinoma (HGSC) is the genomic inactivation of neurofibromin 1 (NF1). The primary objectives of our study were to survey the prevalence of NF1 inactivation in the principal ovarian carcinoma histotype as well as to evaluate its associations with clinico-pathological parameters and key biomarkers including BRCA1/2 status in HGSC. A recently commercialized NF1 antibody (clone NFC) was orthogonally validated on an automated immunohistochemistry (IHC) platform and IHC was performed on tissue microarrays containing 2140 ovarian carcinoma cases. Expression was interpreted as loss/inactivated (complete or subclonal) versus normal/retained. Loss of NF1 expression was detected in 250/1429 (17.4%) HGSC including 11% with subclonal loss. Survival of NF1-inactivated HGSC patients was intermediate between favorable BRCA1/2 mutated HGSC and unfavorable CCNE1 high-level amplified HGSC. NF1 inactivation was mutually exclusive with CCNE1 high-level amplifications, co-occurred with RB1 loss and occurred at similar frequencies in BRCA1/2 mutated versus wild-type HGSC. NF1 loss was found in 21/286 (7.3%) endometrioid carcinomas with a favorable prognostic association (p = 0.048), and in 4/64 (5.9%) LGSC, mutually exclusive with other driver events. NF1 inactivation occurs in a significant subset of BRCA1/2 wild-type HGSC and a subset of LGSC. While the functional effects of NF1 inactivation need to be further characterized, this signifies a potential therapeutic opportunity to explore targeting NF1 inactivation in these tumors. • Orthogonally validated a clinically ready NF1 immunohistochemical assay to survey for NF1 inactivation. • NF1 inactivation occurs in a significant subset of BRCA1/2 wild-type high-grade serous carcinomas. • NF1 inactivation in high-grade serous carcinomas occurs both early in STIC and later during progression as subclonal loss. [ABSTRACT FROM AUTHOR]

In response to a report that testicular cancer incidence in non-Hispanic White mates in Los Angeles county had fallen in the 1990s, particularly in young men, the authors analyzed data collected by the Surveillance, Epidemiology, and End Results (SEER) program from 1973 to 1995. While the incidence rate of testicular cancer in US White males ages 15–64 years did stabilize in the first half of the 1990s, after a number of years of a steady increase, there was no indication of an actual decline. Am J Epidemiol 1999;150:45–6. [ABSTRACT FROM PUBLISHER]

Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC. [ABSTRACT FROM AUTHOR]

Background Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. Methods We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses' Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O]   =   1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O   =   1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O   =   0.55, 95% CI = 0.51 to 0.59). Conclusions Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations. [ABSTRACT FROM AUTHOR]

Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01–1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99–1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12–19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women. • We conducted an individual-participant data meta-analysis of dietary omega-3 fatty acids and endometrial cancer risk. • Data were obtained from 12 prospective cohort studies. • Small, positive associations between dietary omega-3 fatty acids and endometrial cancer were observed overall. • Stronger, moderate positive associations were observed among participants with body mass indices ≥25 kg/m2. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction and inflammation have been associated with endometrial cancer risk; however, their influence on endometrial cancer survival is less understood. Methods: A prospective cohort study of 540 endometrial cancer cases diagnosed between 2002 and 2006 in Alberta were followed for survival outcomes to 2019. Baseline blood samples collected either pre‐ or post‐hysterectomy were analyzed for glucose, insulin, adiponectin, leptin, tumor necrosis factor‐α, interleukin‐6, and C‐reactive protein. Covariates were obtained during in‐person interviews and via medical chart abstraction. Cox proportional hazard regression models were used to estimate multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between each biomarker and disease‐free and overall survival. Results: Blood samples were collected from 520 of the 540 participants (presurgical n = 235; postsurgical n = 285). During the median follow‐up of 14.3 years (range 0.4–16.5 years), there were 125 recurrences, progressions, and/or deaths with 106 overall deaths. None of the biomarkers were associated with disease‐free or overall survival in multivariable‐adjusted analyses. In an exploratory stratified analysis, the highest level of presurgical adiponectin, compared to the lowest level, was associated with improved disease‐free (HR = 0.42, 95% CI = 0.20–0.85) and overall (HR = 0.41, 95% CI = 0.18–0.92) survival, whereas no statistically significant associations were noted for postsurgical measures of adiponectin. Conclusions: Overall, there was no evidence of an association between biomarkers of insulin resistance and inflammation with mortality outcomes in endometrial cancer survivors. Future cohort studies with serial blood samples are needed to understand the impact of changes in insulin resistance and inflammatory markers on endometrial cancer survival. [ABSTRACT FROM AUTHOR]

Background: Disease-free survival (DFS) and overall survival (OS) associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer survivors.Methods: Endometrial cancer survivors diagnosed between 2002 and 2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peridiagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed-up until death or March 20, 2019. Cox proportional regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with DFS and OS. Statistical tests were 2-sided.Results: A total of 540 and 425 cancer survivors were assessed peridiagnosis and follow-up, respectively. During the median 14.2 years of follow-up (range = 0.3-16.5 years), 132 participants had a recurrence and/or died (DFS), with 111 deaths overall (OS). Reduced DFS was noted with greater recalled weight 1 year before diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI 1 year before diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peridiagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peridiagnosis waist circumference of at least 88 cm was associated with decreased DFS (HR = 1.94, 95% CI = 1.24 to 3.03) and OS (HR = 1.90, 95% CI = 1.16 to 3.13). A twofold decrease in DFS and OS was associated with a BMI of at least 5% or weight change from 1 year before diagnosis to peridiagnosis. No associations were observed for the assessment during follow-up.Conclusions: One-year before- and peridiagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from 1 year before to peridiagnosis may provide an important indication of future survival in this population. [ABSTRACT FROM AUTHOR]

Racial and ethnic disparities in chronic obstructive pulmonary disease (COPD) are not well-studied. Our objective was to examine differences in limited COPD-related outcomes between three minority groups—African Americans (AAs), Hispanics, and American Indians (AIs) versus non-Hispanic Whites (NHWs), as the referent group, in separate cohorts. Separate cross-sectional evaluations were performed of three US-based cohorts of subjects at risk for COPD: COPDGene Study with 6,884 NHW and 3,416 AA smokers; Lovelace Smokers' Cohort with 1,598 NHW and 378 Hispanic smokers; and Mining Dust Exposure in the United States Cohort with 2,115 NHW, 2,682 Hispanic, and 2,467 AI miners. Prebronchodilator spirometry tests were performed at baseline visits using standard criteria. The primary outcome was the prevalence of airflow obstruction. Secondary outcomes were self-reported physician diagnosis of COPD, chronic bronchitis, and modified Medical Research Council dyspnea score. All minority groups had a lower prevalence of airflow obstruction than NHWs (adjusted ORs varied from 0.29 in AIs to 0.85 in AAs; p < 0.01 for all analyses). AAs had a lower prevalence of chronic bronchitis than NHWs. In our study, all minority groups had a lower prevalence of airflow obstruction but a greater level of self-reported dyspnea than NHWs, and covariates did not explain this association. A better understanding of racial and ethnic differences in smoking-related and occupational airflow obstruction may improve prevention and therapeutic strategies. [ABSTRACT FROM AUTHOR]

ObjectiveIntake of nutrients may influence the risk of endometrial cancer (EC). We aimed to estimate the association of intake of individual nutrients from food and from food plus supplements with EC occurrence.DesignA population-based case–control study conducted in Canada (2002–2006).SettingNutrient intakes from food and supplements were assessed using an FFQ. Logistic regression was used to estimate EC risk within quartile levels of nutrient intakes.SubjectsIncident EC cases (n 506) were identified from the Alberta Cancer Registry, and population controls were frequency- and age-matched to cases (n 981).ResultsThere existed little evidence of an association with EC for the majority of macronutrients and micronutrients examined. We observed a statistically significant increased risk associated with the highest, compared with the lowest, quartile of intake of dietary cholesterol (multivariable-adjusted OR = 1·51, 95 % CI 1·08, 2·11; P for trend = 0·02). Age-adjusted risk at the highest level of intake was significantly reduced for Ca from food sources (OR = 0·73, 95 % CI 0·54, 0·99) but was attenuated in the multivariable model (OR = 0·82, 95 % CI 0·59, 1·13). When intake from supplements was included in Ca intake, risk was significantly reduced by 28 % with higher Ca (multivariable-adjusted OR = 0·72, 95 % CI 0·51, 0·99, P for trend = 0·04). We also observed unexpected increased risks at limited levels of intakes of dietary soluble fibre, vitamin C, thiamin, vitamin B6 and lutein/zeaxanthin, with no evidence for linear trend.ConclusionsThe results of our study suggest a positive association between dietary cholesterol and EC risk and an inverse association with Ca intake from food sources and from food plus supplements. [ABSTRACT FROM PUBLISHER]

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci. We found significant genetic correlation between endometrial cancer and PCOS, and uterine fibroids. Adjustment for genetically predicted body mass index (a risk factor for PCOS, uterine fibroids and endometrial cancer) substantially attenuated the genetic correlation between endometrial cancer and PCOS but did not affect the correlation with uterine fibroids. Mendelian randomization analyses suggested a causal relationship between only uterine fibroids and endometrial cancer. Gene-based analyses revealed risk regions shared between endometrial cancer and endometriosis, and uterine fibroids. Multi-trait GWAS analysis of endometrial cancer and the genetically correlated gynecological diseases identified a novel genome-wide significant endometrial cancer risk locus at 1p36.12, which replicated in an independent endometrial cancer dataset. Interrogation of functional genomic data at 1p36.12 revealed biologically relevant genes, including WNT4 which is necessary for the development of the female reproductive system. In summary, our study provides genetic evidence for a causal relationship between uterine fibroids and endometrial cancer. It further provides evidence that the comorbidity of endometrial cancer, PCOS and uterine fibroids may partly be due to shared genetic architecture. Notably, this shared architecture has revealed a novel genome-wide risk locus for endometrial cancer. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity among miners. There is an increasing number of women in the mining industry and the differences in their risk for COPD compared to men miners are not understood. Our objective is to compare the odds for COPD between male and female miners. Using cross-sectional data from the Mining Dust in the United States (MiDUS) Cohort, that included New Mexico miners between 1989 and 2018, we compared the odds for airflow obstruction or chronic bronchitis between women and men. There were 299 women in this diverse cohort of 7,464 miners. Compared to men, female miners reported lower cumulative smoking but higher prevalence of current smoking. Multivariable analysis showed that women miners had significantly lower odds for having airflow obstruction (OR 0.40; 95% CI (0.26, 0.6)) and chronic bronchitis (OR 0.31, 95% CI (0.19, 0.53)) than men. Future studies need to determine whether this sex difference is explained by residual confounders or true biological difference. [ABSTRACT FROM AUTHOR]

Comorbidities are known to increase endometrial cancer risk, but the separate and combined impact of these risk factors on endometrial cancer survival remains unclear. This study aimed to determine the associations between metabolic syndrome and its components with disease-free survival, overall survival, endometrial cancer-specific survival and recurrence among endometrial cancer survivors. Cases from a population-based case-control study who were diagnosed with primary endometrial cancer between 2002 and 2006 in Alberta, Canada were followed until death or March 20, 2019. Baseline in-person interviews, direct anthropometric measurements and fasting blood samples were used to assess metabolic syndrome (presence of ≥3 of the following: waist circumference ≥ 88 cm, fasting blood glucose ≥100 mg/dL, triglycerides ≥150 mg/dL, high-density lipoprotein cholesterol <50 mg/dL and self-reported hypertension). Cox proportional hazards regression and Fine and Gray competing risk models were used to estimate multivariate-adjusted hazard ratios (95% CI) for these associations. Among 540 endometrial cancer survivors, 325 had metabolic syndrome at diagnosis and 132 had a recurrence and/or died during the median 14.2 years of follow-up (range: 0.3–16.5 years). In multivariable analyses, being diagnosed with metabolic syndrome (HR = 1.98, 95% CI = 1.07–3.67) and having an elevated waist circumference (≥88 cm; HR = 2.12, 95% CI = 1.18–3.80; HR per 5 cm = 1.21, 95% CI = 1.07–1.36) were associated with worse overall survival. Additionally, increasing waist circumference (per 5 cm) was also associated worse with disease-free survival (HR per 5 cm = 1.11, 95% CI = 1.00–1.24). The metabolic syndrome, in particular central adiposity, were associated with worse overall and disease-free survival in endometrial cancer survivors. • Endometrial cancer survivors with metabolic syndrome had worse overall survival compared to those without this syndrome. • Elevated waist circumference was the only metabolic syndrome component associated with worse survival outcomes. • Greater lifetime physical activity improved survival outcomes despite metabolic syndrome risk factors. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of chronic obstructive pulmonary disease (COPD) between miners extracting coal versus other minerals. Methods: The study population was based on New Mexico miners, mostly Hispanic and American Indian, attending a rural community-based mobile screening clinic program between 1989 and 2014. We compared selfreported symptoms, lung diseases, and spirometric patterns between 1353 coal miners and 4140 non-coal miners. Results: Obstruction was the most common abnormal spirometric pattern among all miners (16.9%). Coal miners were more likely to demonstrate an obstructive pattern and report chronic bronchitis symptoms than non-coal miners (adjusted odds ratio [OR] = 1.24, 95% confidence interval [CI]: 1.03, 1.48; and OR=1.47, 95% CI: 1.24, 1.75, respectively). These associations remained significant among never smoking miners. Conclusions: The prevention and management of COPD among coal miners deserves greater emphasis by rural health care delivery systems. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test the hypothesis that uranium miners in New Mexico (NM) have a greater prevalence of cardiovascular disease than miners who extracted the nonuranium ore. Methods: NM-based current and former uranium miners were compared with nonuranium miners by using cross-sectional standardized questionnaire data from the Mining Dust in the United States (MiDUS) study from 1989 to 2016. Results: Of the 7215 eligible miners, most were men (96.3%). Uranium miners (n = 3151,43.7%) were older and diabetic, but less likely to currently smoke or use snuff (P < 0.001 for all). After adjustment for covariates, uranium miners were more likely to report angina (odds ratio 1.51, 95% confidence interval 1.23 to 1.85) than nonuranium miners. Conclusion: Our data suggest that along with screening for pulmonary diseases, uranium industry workers should be screened for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between breastfeeding and endometrial cancer risk using pooled data from 17 studies participating in the Epidemiology of Endometrial Cancer Consortium.Methods: We conducted a meta-analysis with individual-level data from three cohort and 14 case-control studies. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between breastfeeding and risk of endometrial cancer using multivariable logistic regression and pooled using random-effects meta-analysis. We investigated between-study heterogeneity with I  and Q statistics and metaregression.Results: After excluding nulliparous women, the analyses included 8,981 women with endometrial cancer and 17,241 women in a control group. Ever breastfeeding was associated with an 11% reduction in risk of endometrial cancer (pooled OR 0.89, 95% CI 0.81-0.98). Longer average duration of breastfeeding per child was associated with lower risk of endometrial cancer, although there appeared to be some leveling of this effect beyond 6-9 months. The association with ever breastfeeding was not explained by greater parity and did not vary notably by body mass index or histologic subtype (grouped as endometrioid and mucinous compared with serous and clear cell).Conclusion: Our findings suggest that reducing endometrial cancer risk can be added to the list of maternal benefits associated with breastfeeding. Ongoing promotion, support, and facilitation of this safe and beneficial behavior might therefore contribute to the prevention of this increasingly common cancer. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis.Methods: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals).Results: The PAX8-target gene set was ranked 1/615 in the discovery (PGSEA<0.001; FDR=0.21), 7/615 in the replication (PGSEA=0.004; FDR=0.37), and 1/615 in the combined (PGSEA<0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10-5 (including six with P<5 × 10-8). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (PGSEA=0.025) and IGROV1 (PGSEA=0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation.Conclusions: Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC. [ABSTRACT FROM AUTHOR]

Background: Prospective cohorts have the potential to support multifactorial, health-related research, particularly if they are drawn from the general population, incorporate active and passive follow-up and permission is obtained to allow access by researchers to data repositories. This paper describes Phase I of the Alberta’s Tomorrow Project cohort, a broad-based research platform designed to support investigations into factors that influence cancer and chronic disease risk. Methods: Adults aged 35–69 years living in Alberta, Canada, with no previous cancer diagnosis other than nonmelanoma skin cancer were recruited to the project by telephone-based random digit dialling. Participants were enrolled if they returned a Health and Lifestyle Questionnaire. Past year diet and physical activity questionnaires were mailed 3 months after enrolment. Consent was sought for active follow-up and linkage with administrative databases. Depending on enrolment date, participants were invited to complete up to 2 follow-up questionnaires (2004 and 2008). Results: Between 2001 and 2009, 31 072 (39% men) participants (mean age 50.2 [± 9.2] yr) were enrolled and 99% consented to linkage with administrative databases. Participants reported a wide range of educational attainment and household income. Compared with provincial surveillance data from the Canadian Community Health Survey, Alberta’s Tomorrow Project participants had higher body mass index, lower prevalence of smoking and similar distribution of chronic health conditions. Follow-up questionnaires were completed by 83% and 72% of participants in 2004 and 2008, respectively. Robust quality control measures resulted in low frequencies of missing data. Interpretation: Alberta’s Tomorrow Project provides a robust platform, based on a prospective cohort design, to support research into risk factors for cancer and chronic disease. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10−5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk. [ABSTRACT FROM AUTHOR]

Background: Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. Methods/Design: The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. Discussion: The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions. [ABSTRACT FROM AUTHOR]

introduction: The evidence for a role of dietary carbohydrate intake with endometrial cancer risk is conflicting. We therefore evaluated the association between glycemic load (GL) and endometrial cancer in a population-based-case control study using a comprehensive quantitative food frequency questionnaire for the estimation of GL. Methods: Diet in the year before the reference date was assessed with the self-administered Canadian Diet History Questionnaire in 511 cases and 980 controls in Alberta, Canada between 2002 and 2006. Multivariable logistic regression was used to examine the association between GL and endometrial cancer risk, with non-linearity evaluated by the examination of cubic splines. Results: The risk for endometrial cancer did not change based on GL (for the highest versus lowest quartile, adjusted odds ratio = 0.87, 95% confidence interval = 0.52-1.46), even after the removal of participants previously diagnosed with diabetes ((diabetics n cases = 63, n controls = 55 excluded) adjusted odds ratio = 0.77, 95% confidence interval = 0.44-1.36). We observed no evidence of effect modification by Body Mass Index (BMI)(p-interaction term = 0.22). Conclusions: Intake of foods eliciting a glycemic response was not associated with endometrial cancer risk in this population of Canadian women. [ABSTRACT FROM AUTHOR]

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10 −31 ) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC. [ABSTRACT FROM AUTHOR]

Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002–2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (≥30) body mass index (weight (kg)/height (m)2) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index. [ABSTRACT FROM PUBLISHER]

Markers of insulin resistance such as the adiponectin:leptin ratio (A:L) and the homeostasis model assessment ratio (HOMA-IR) are associated with obesity and hyperinsulinemia, both established risk factors for endometrial cancer, and may therefore be informative regarding endometrial cancer risk. This study investigated the association between endometrial cancer risk and markers of insulin resistance, namely adiponectin, leptin, the A:L ratio, insulin, fasting glucose, and the HOMA-IR. We analyzed data from 541 incident endometrial cancer cases and 961 frequency agematched controls in a population-based case-control study in Alberta, Canada from 2002 to 2006. Participants completed interview-administered questionnaires were assessed for anthropometric measures, and provided 8-h fasting blood samples either pre- or postoperatively. Blood was analyzed for concentrations of leptin, adiponectin, and insulin by immunoassay, and fasting plasma glucose levels were determined by fluorimetric quantitative determination. Compared with the lowest quartile, the highest quartile of insulin and HOMA-IR was associated with 64% (95% confidence intervals (CI): 1.12-2.40) and 72% (95% CI: 1.17-2.53) increased risks of endometrial cancer, respectively, and the highest quartile of adiponectin was associated with a 45% (95% CI: 0.37-0.80) decreased risk after multivariable adjustments. Null associations were observed between fasting glucose, leptin and A:L, and endometrial cancer risk. This population-based study provides evidence for a role of insulin resistance in endometrial cancer etiology and may provide one possible pathway whereby obesity increases the risk of this common cancer. Interventions aimed at decreasing both obesity and insulin resistance may decrease endometrial cancer risk. [ABSTRACT FROM AUTHOR]

The article presents a study on the interaction of CDKN2A and sun exposure to the etiology of melanoma. It states that 3,624 melanoma patients from nine centers from four countries were recruited for the study to identify how the two factors might increase the risk of melanoma. The study found no evidence suggesting the influence of CDKN2A mutational status and sun exposure on the risk of melanoma.

Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ≤ 10−4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ≤ 5 × 10−8 (8q24, P = 8.0 × 10−15 and 2q31, P = 3.8 × 10−14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10−8 and 17q21, P = 1.4 × 10−7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development. [ABSTRACT FROM AUTHOR]

Objective: To describe the association between intima-media thickness (IMT) and metabolic syndrome (MetS) and to examine if the addition of IMT to a traditional MetS definition adds value to the assessment of predicted cardiovascular disease (CVD) risk in a large multiethnic population.Participants and Methods: In this cross-sectional study, carotid IMT was measured in 2268 men and women as part of a wellness physical examination between August 1, 2000, and October 1, 2001. The wellness examination included a fasting lipid panel, physical examination, and medical history. Mean IMT was described by sex, ethnicity, and the MetS. Predicted risk for CVD was determined with IMT as a component of the diagnostic criteria for MetS.Results: Intima-media thickness increased with each additional component of the MetS, increasing from 0.516 mm for 0 components to 0.688 mm for 4 or more components (P<.001). In each ethnic group (non-Hispanic whites, blacks, Hispanics, and Asians), those with the MetS had higher mean IMT (increased by 0.084 mm to 0.134 mm) than those without MetS. The addition of IMT as a "new" component in the diagnosis of MetS allowed us to identify 78 (3.4%) participants who were not previously diagnosed as having MetS but who had a high 10-year estimated risk of MetS as measured by the Framingham risk score (11.67%).Conclusion: The addition of IMT to the traditional criteria for the diagnosis of the MetS may help identify individuals who otherwise would not have been identified to be at high risk of CVD. [ABSTRACT FROM AUTHOR]

Purpose: Information obtained by telephone interviews and in-person interviews is generally considered comparable, but it is unclear if extensive memory aids can be used effectively with telephone interviews. We compared a telephone interview to an in-person interview using the same questionnaire and memory aids in both.Methods: A convenience sample of 103 women, aged 25 to 69 years, completed a telephone interview and at least four weeks later, completed an in-person interview. Memory aids included a life events calendar, cue lists, and worksheets.Results: Agreement values, measured by kappa/weighted kappa, were as follows: parity (1.00), age at menarche (0.76), menopausal status (0.95), a history of reproductive organ surgery (0.98) or tubal ligation (0.91), self-reported infertility (0.76), and a first degree family history of breast/ovarian cancer (0.90). Agreement values for duration variables, measured by the intraclass correlation, were as follows: lactation (0.96), oral contraceptive use (0.98), any hormone replacement therapy (0.98), exclusive estrogen and progesterone therapy (0.83), and exclusive estrogen therapy (0.99).Conclusions: The good to excellent level of agreement found in this study indicates that telephone administration of our questionnaire with extensive memory aids is a reliable method of obtaining detailed exposure information relative to in-person interviews. [ABSTRACT FROM AUTHOR]

The United States has a rich history of mining including uranium (U)-mining, coal mining, and other metal mining. Cardiovascular diseases (CVD) are largely understudied in miners and recent literature suggests that when compared to non-U miners, U-miners are more likely to report CVD. However, the molecular basis for this phenomenon is currently unknown. In this pilot study, a New Mexico (NM)-based occupational cohort of current and former miners (n = 44) were recruited via a mobile screening clinic for miners. Serum- and endothelial-based endpoints were used to assess circulating inflammatory potential relevant to CVD. Non-U miners reported significantly fewer pack years of smoking than U-miners. Circulating biomarkers of interest revealed that U-miners had significantly greater serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (ICAM-1, ng/mL), soluble vascular cell adhesion molecule 1 (VCAM-1, ng/mL), and VCAM-1 mRNA expression, as determined by the serum cumulative inflammatory potential (SCIP) assay, an endothelial-based assay. Even after adjusting for various covariates, including age, multivariable analysis determined that U-miners had significantly upregulated VCAM-1 mRNA. In conclusion, VCAM-1 may be an important biomarker and possible contributor of CVD in U-miners. Further research to explore this mechanism may be warranted. [ABSTRACT FROM AUTHOR]