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Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic is a health crisis of which older adults are a high-risk group for severe illness and mortality. The objectives of this article are to describe the methods and responses to a COVID-19 survey administered by the Women's Health Initiative (WHI) to assess the impact of the pandemic on older women.Methods: WHI is an ongoing prospective cohort study that recruited 161 808 postmenopausal women from 1993 to 1998. From June 2020 to October 2020, participants in active follow-up were surveyed by mail, phone, or online to assess health and well-being, living situations, lifestyle, health care, and self-reported COVID-19 testing, treatment, and preventive behaviors.Results: Of 64 061 eligible participants, 49 695 (average age 83.6 years ± 5.6) completed the COVID-19 survey (response rate 77.6%). Many participants reported very good or good well-being (75.6%). Respondents reported being very concerned about the pandemic (51.1%; more common in urban compared to rural areas), with 6.9% reporting disruptions in living arrangements and 9.7% reporting changes in medication access. Participants (54.4%) reported physical activity levels were much less or somewhat less compared to levels before the pandemic, and this was more pronounced in urban areas versus rural areas (55.3% vs 44.4%). Participants engaged in preventive behaviors including wearing a face mask (93.2%). A total of 18.9% reported testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among whom 3.5% (n = 311) reported testing positive.Conclusions: In this nationwide survey of older U.S. women, the COVID-19 pandemic was associated with impacts on health and well-being, living situations, lifestyle, health care access, and SARS-CoV-2 testing and preventive behaviors. [ABSTRACT FROM AUTHOR]

Endometriosis, psoriasis, and psoriatic arthritis (PsA) are chronic inflammatory disorders whose etiologies remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bidirectional associations between laparoscopically confirmed endometriosis and physician-diagnosed psoriasis and PsA in the Nurses' Health Study II cohort (n  = 116,429, United States, 1991–2013). We confirmed 4,112 incident cases of laparoscopically confirmed endometriosis (mean age at diagnosis = 40.3 years) and 697 validated physician-diagnosed cases of psoriasis (mean age at diagnosis = 43.6 years), 110 of which presented with concomitant PsA. A history of psoriasis with concomitant PsA was associated with a 2-fold higher risk of endometriosis (hazard ratio (HR) = 2.01, 95% CI: 1.23, 3.30); however, no association was observed between psoriasis without PsA and endometriosis risk (HR = 0.93, 95% CI: 0.68, 1.26). When endometriosis was the exposure, it was not associated with a risk of subsequent psoriasis (HR = 1.28, 95% CI: 0.95, 1.72). The risk of psoriasis with PsA was notably higher; however, the sample size was small and the confidence intervals wide (HR = 1.77, 95% CI: 0.89, 3.52). Our findings suggest that psoriasis with concomitant PsA is associated with greater risk of laparoscopically confirmed endometriosis. In addition, there was a suggestive association between endometriosis diagnosis and subsequent risk of psoriasis with PsA. [ABSTRACT FROM AUTHOR]

Background: Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. Methods: The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swedish Mammography Cohort (SMC), aged 45-83 years at baseline. The COSM was established in 1997 with all men who lived in two central Swedish counties (Västmanland and Örebro), and the SMC was established in 1987-1990 with women residing in Västmanland county. Tea consumption was assessed by means of food frequency questionnaires in 1997 and 2009. Results: During 17.5 years of follow-up, 1781 AAA cases (1496 men, 285 women; 1497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. Tea consumption was inversely associated with total AAA incidence in men and women. Women had a 23 (95 per cent c.i. 8 to 36) per cent lower risk of AAA per each cup per day increment, whereas men had a 9 (0 to 17) per cent lower risk (Pinteraction=0.029). Tea consumption was associated with a lower risk of both non-ruptured (hazard ratio (HR) 0.93, 95 per cent c.i. 0.85 to 1.01) and ruptured (HR 0.84, 0.71 to 0.98) AAA. Smoking status modified the association (Pinteraction,0.001), whereby tea consumption was associated with lower risk of AAA in ex-smokers (per cup per day, HR 0.89, 0.80 to 0.98) and in never smokers (HR 0.88, 0.77 to 1.00), but not in current smokers (HR 0.95, 0.84 to 1.06). Tea consumption was associated with a lower risk in participants with (HR 0.88, 0.80 to 0.98) and without (HR 0.93, 0.88 to 1.00) hypertension, and in those with (HR 0.82, 0.67 to 1.01) and without (HR 0.92, 0.86 to 0.98) hypercholesterolaemia. Conclusion: Tea consumption was associated with a reduced risk of AAA. The association was more pronounced for ruptured than non-ruptured AAA, and in patients with hypertension and hypercholesterolaemia than those without. The association was also observed in ex-smokers and never smokers, but not in current smokers. [ABSTRACT FROM AUTHOR]

Background: The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women.Methods: We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided.Results: Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% confidence interval [CI] = 6.5% to 13.7%) compared with White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including body mass index, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04).Conclusions: Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is an often chronic, inflammatory gynaecologic condition affecting 190 million women worldwide. Studies have reported an elevated cancer risk among patients with endometriosis. However, prior research has included methodologic issues that impede valid and robust interpretation.Objective and Rationale: We conducted a meta-analysis of studies investigating the association between endometriosis and cancer risk and analysed the results by methodologic characteristics. We discuss the implications of cancer screening in patients and management challenges faced by clinicians.Search Methods: We searched PubMed and Embase databases for eligible studies from inception through 24 October 2019. We included cohort and case-control studies examining the association between endometriosis and cancer risk; cross-sectional studies and case reports were excluded. Publications had to present risk/rate/odds estimates with 95% CI. Random effects meta-analysis was used to estimate summary relative risks (SRR) and CIs. Heterogeneity across studies was assessed by the Q test and I2 statistics, and publication bias using Egger's and Begg's tests. Risk of bias and quality of the included studies were assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.Outcomes: Forty-nine population-based case-control and cohort studies were included. Twenty-six studies were scored as having a 'serious'/'critical' risk of bias, and the remaining 23 'low'/'moderate'. Cancer-specific analyses showed a positive association between endometriosis and ovarian cancer risk (SRR = 1.93, 95% CI = 1.68-2.22; n = 24 studies) that was strongest for clear cell (SRR = 3.44, 95% CI = 2.82-4.42; n = 5 studies) and endometrioid (SRR = 2.33, 95% CI = 1.82-2.98; n = 5 studies) histotypes (Pheterogeneity < 0.0001), although with significant evidence of both heterogeneity across studies and publication bias (Egger's and Begg's P-values < 0.01). A robust association was observed between endometriosis and thyroid cancer (SRR = 1.39, 95% CI =1.24-1.57; n = 5 studies), a very small association with breast cancer (SRR = 1.04, 95% CI =1.00-1.09; n = 20 studies) and no association with colorectal cancer (SRR = 1.00, 95% CI =0.87-1.16; n = 5 studies). The association with endometrial cancer was not statistically significant (SRR = 1.23, 95% CI =0.97-1.57; n = 17 studies) overall and wholly null when restricted to prospective cohort studies (SRR = 0.99, 95% CI =0.72-1.37; n = 5 studies). The association with cutaneous melanoma was also non-significant (SRR = 1.17, 95% CI =0.97-1.41; n = 7 studies) but increased in magnitude and was statistically significant when restricted to studies with low/moderate risk of bias (SRR = 1.71, 95% CI = 1.24-2.36, n = 2 studies). The most robust finding both in terms of statistical significance and magnitude of effect was an inverse association with cervical cancer (SRR = 0.68, 95% CI =0.56-0.82; n = 4 studies); however, this result has a high potential to reflect heightened access to detection of dysplasia for women who reached an endometriosis diagnosis and is thus likely not causal. Several additional cancer types were explored based on <4 studies.Wider Implications: Endometriosis was associated with a higher risk of ovarian and thyroid, and minimally (only 4% greater risk) with breast cancer, and with a lower risk of cervical cancer. However, this meta-analysis confirms that: a majority of studies had severe/critical risk of bias; there is impactful heterogeneity across studies-and for ovarian cancer, publication bias; and causal inference requires temporality, which in many studies was not considered. We discuss the implications of these potential associations from the perspectives of patients with endometriosis, clinicians involved in their care, and scientists investigating their long-term health risks. [ABSTRACT FROM AUTHOR]

Study Question: Is recreational and residential sun exposure associated with risk of endometriosis?Summary Answer: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk.What Is Known Already: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk.Study Design, Size, Duration: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015.Participants/materials, Settings, Methods: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs.Main Results and the Role Of Chance: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252  248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis.Limitations, Reasons For Caution: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records.Wider Implications Of the Findings: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology.Study Funding/competing Interest(s): This project was supported by NICHD grants HD48544 and HD52473, HD57210, NIH grant CA50385, CA176726. M.K. was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. H.R.H. is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). The authors have nothing to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer.Methods: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls).Results: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations.Conclusion: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association. [ABSTRACT FROM AUTHOR]

Studies indicate an inverse association between moderate alcohol consumption and chronic inflammatory diseases; however, the association between alcohol consumption and chronic obstructive pulmonary disease (COPD) incidence has not been widely studied. We investigated the associations of total alcohol consumption and intake of specific alcoholic beverages with risk of COPD in a population-based prospective cohort study, the Cohort of Swedish Men (n = 44,254). Alcohol consumption was assessed with a self-administered questionnaire in 1997. During follow-up (1998–2014), 2,177 COPD cases were ascertained. Moderate alcohol consumption was associated with the lowest risk of COPD. A J-shaped association was observed for ethanol consumption (P for nonlinearity = 0.003) and beer consumption (P for nonlinearity < 0.001); for wine consumption, a U-shaped association was observed (P for nonlinearity < 0.001). Defining a "standard drink" as 12 g of ethanol, the multivariable-adjusted hazard ratios were 0.77 (95% confidence interval (CI): 0.66, 0.90) and 0.92 (95% CI: 0.81, 1.05) for beer consumption of 4.1–6.0 and >6.0 standard drinks/week (SDW) versus <1.0 SDW, respectively; 0.80 (95% CI: 0.69, 0.93) and 1.00 (95% CI: 0.83, 1.21) for wine consumption of 2.0–4.0 and >4.0 SDW versus <1.0 SDW, respectively; and 1.10 (95% CI: 0.98, 1.24) and 1.20 (95% CI: 0.99, 1.44) for liquor consumption of 2.0–4.0 and >4.0 SDW versus <1.0 SDW, respectively. In conclusion, our findings suggest that moderate beer and wine consumption, but not liquor consumption, may decrease risk of COPD. Additional studies are needed to confirm these associations. [ABSTRACT FROM AUTHOR]

Background: The understanding of ovarian cancer pathogenesis has recently shifted to recognize distinct changes in how ovarian cancer histotypes are defined. Using the 2014 World Health Organization (WHO) diagnostic guidelines, we classified ovarian cancer histotypes in Surveillance, Epidemiology, and End Results (SEER) cancer registry data and examined survival patterns by histotype and disease stage.Methods: We extracted data on 28 118 incident epithelial ovarian cancer cases diagnosed in 2004-2014 from SEER and defined histotype using the 2014 WHO guidelines (high-grade serous, low-grade serous, endometrioid, clear cell, mucinous, carcinosarcoma, and malignant Brenner tumors). By histotype and disease stage, we estimated Kaplan-Meier survival curves and calculated age-adjusted overall and cause-specific survival estimates. Cox proportional hazards regression models were used to estimate histotype-specific hazard ratios (HRs) and 95% confidence intervals (CIs) by disease stage while adjusting for age at diagnosis, region, race/ethnicity, and receipt of surgery.Results: Within two years after diagnosis, localized/regional-stage carcinosarcoma and distant-stage mucinous, clear cell, and carcinosarcoma had a higher risk of mortality compared with high-grade serous, with the most pronounced association for localized/regional carcinosarcoma (>1-2-year time period: HR = 3.81, 95% CI = 2.74 to 5.30) and distant-stage mucinous (0-1-year time period: HR = 3.87, 95% CI = 3.45 to 4.34). In the time period more than four to 10 years after diagnosis, hazard ratios for all histotypes relative to high-grade serous, irrespective of disease stage, were less than 1.00. Cumulatively, both localized/regional and distant-stage low-grade serous and endometrioid carcinomas had the most favorable outcomes.Conclusions: Our large study, which is representative of the United States population and incorporates the most current knowledge of ovarian cancer pathogenesis, highlights the need to recognize ovarian cancer as a set of distinct diseases and not a single entity. Only then will we be able to effectively target the unique features of each histotype to reduce ovarian cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Fruits and vegetables, due to high antioxidant capacity, may protect the lung from oxidative damage caused by tobacco smoke and potentially prevent chronic obstructive pulmonary disease (COPD). Only one study based on baseline diet has examined fruit and vegetable consumption in relation to risk of COPD, and no previous studies have examined long-term diet.Methods: We investigated whether long-term fruit and vegetable consumption was associated with COPD incidence among 34 739 women (age 48-83 years) in the population-based prospective Swedish Mammography Cohort. Fruit and vegetable consumption was assessed twice (1987, 1997) with a self-administered questionnaire. Cases of COPD were identified by linkage to the Swedish health register. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During follow-up from 2002 to 2014, 1512 women were diagnosed with COPD. Long-term fruit was associated with lower risk of COPD; women in the highest vs lowest quintile of consumption (≥2.5 vs <0.8 servings/day) had a 37% lower risk of COPD (95% CI: 25-48%; P-trend < 0.0001). No association was observed with long-term vegetable intake. Current and ex-smokers with low long-term consumption of fruits (<1 serving/day) in comparison to never smokers with high consumption (≥3 servings/day) had a 38-fold (HR: 38.1; 95% CI: 20.2-71.7) and 13-fold (HR: 12.5, 95% CI: 6.5-24.1) higher risk of COPD, respectively. However, no significant interaction between smoking status and fruit intake in relation to COPD incidence was observed (P-interaction = 0.95).Conclusions: In this prospective cohort of middle-age and older women, long-term consumption of fruits but not vegetables was inversely associated with COPD incidence. [ABSTRACT FROM AUTHOR]

Objective: Child fussy eating has been associated with a range of maternal feeding practices; however, whether effects are parent-driven, child-driven, or bidirectional (i.e., both) remains unclear. This study tested for bidirectional relationships between nonresponsive and structure-related maternal feeding practices and child fussy eating at age 2, 3.7, and 5 years using a cross-lagged model approach.Methods: First-time Australian mothers (N = 207) reported four nonresponsive and four structure-related feeding practices and child food fussiness (FF) using validated questionnaires at child age 2, 3.7, and 5 years. Bivariate cross-lagged analyses were conducted for each of the eight feeding practices separately.Results: Both child- and parent-driven associations were observed. Higher FF at 3.7 years predicted higher nonresponsive feeding practices and less structure-related practices at 5 years. Higher structure-related practices at 2 and 3.7 years predicted lower FF at 3.7 and 5 years, respectively. Use of food as a reward for behavior at 3.7 years predicted higher FF at 5 years.Conclusions: Both parent- and child-driven associations explain the relationship between fussy eating and feeding practices. Given that early fussy eating is associated with more nonresponsive feeding, providing parents with anticipatory guidance to manage fussy eating behavior in infants and toddlers may help to avoid the use of these practices. Furthermore, the use of structure-related feeding practices and avoiding the use of food rewards may help to prevent the development of fussy eating. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between physical and sexual abuse occurring in childhood or adolescence and risk of laparoscopically-confirmed endometriosis?Summary Answer: Early life sexual and physical abuse was associated with an increased risk of endometriosis.What Is Known Already: Previous studies have reported that physical and sexual abuse are associated with chronic pelvic pain (CPP). However, only one study has examined the association between childhood physical abuse and laparoscopically-confirmed endometriosis, and did not observe an association with endometriosis risk.Study Design, Size, Duration: Prospective cohort study using data collected from 60 595 premenopausal women from 1989 to 2013 as part of the Nurses' Health Study II cohort.Participants/materials, Setting, Methods: Participants completed an exposure to violence victimization questionnaire in 2001. Cases were restricted to laparoscopically-confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% confidence intervals (CI).Main Results and the Role Of Chance: Three thousand three hundred and ninety-four cases of laparoscopically-confirmed endometriosis were diagnosed during 24 years of follow-up. Compared to those reporting no physical or sexual abuse, the risk of endometriosis was greater among those who experienced severe physical abuse (RR = 1.20; 95% CI = 1.06, 1.37) or severe sexual abuse (RR = 1.49; 95% CI = 1.24, 1.79). There was a 79% increased risk of laparoscopically-confirmed endometriosis for women reporting severe-chronic abuse of multiple types (95% CI = 1.44, 2.22). The associations between abuse and endometriosis were stronger among women presenting without infertility, a group that was more likely to have been symptomatic with respect to pain.Limitations, Reasons For Caution: The violence exposure was recalled by the study participants and thus is subject to misclassification as well as recall bias for the cases who were diagnosed prior to 2001. However, our results were similar in a sensitivity analysis including only endometriosis cases incident after their violence history report. In addition, residual or unmeasured confounding is a possibility; however, we were able to adjust for a variety of potential early life confounders. Finally, selection bias is also a possibility if those who chose to return the violence questionnaire did so based jointly on abuse history and endometriosis risk.Wider Implications Of the Findings: Early life sexual and physical abuse was associated with an increased risk of endometriosis. Severity, chronicity and accumulation of types of abuse were associated with greater risk. Understanding the mechanisms underlying these relations may better define the biologic impacts of abuse and the related pathophysiology of endometriosis.Study Funding/competing Interest(s): This work was supported by National Institute of Child Health and Human Development [Grant numbers HD48544, HD52473, HD57210 and CA50385] and the Atlanta Clinical and Translational Science Institute [Grant number ULRR025008]. The Nurses' Health Study II is supported by the National Institutes of Health grant UM1 CA176726 from the National Cancer Institute. H.R.H. is supported by the National Cancer Institute, National Institutes of Health [Grant number K22 CA193860]. Authors report no conflict of interest. [ABSTRACT FROM AUTHOR]

Much evidence suggests a role for inflammation in the pathogenesis of endometriosis. Although investigators in numerous case-control studies have found elevation of inflammatory markers in patients with endometriosis, results were not consistent, and no prior prospective study is known to exist.We conducted a case-control study nested within the Nurses' Health Study II in which we examined associations between levels of plasma inflammatory markers (interleukin-1 beta, interleukin-6, soluble tumor necrosis factor α receptors 1 and 2, and high-sensitivity C-reactive protein) and the risk of laparoscopically confirmed endometriosis. From blood collections in 1996-1999 and 2007, we ascertained 350 cases patients with incident endometriosis and 694 matched controls. Women with interleukin-1 beta levels in quintiles 2-4 had a higher risk of endometriosis (for the second quintile, relative risk (RR) = 3.30, 95% confidence interval (CI): 1.06, 10.3; for the third quintile, RR = 3.36, 95% CI: 1.09, 10.4; and for the fourth quintile, RR = 4.64, 95% CI: 1.58, 13.6; P for trend = 0.62), which suggested an association beginning at 0.47 pg/mL or greater. A significant nonlinear association with levels of soluble tumor necrosis factor α receptor 2 was observed, with elevated risk of endometriosis at concentrations greater than 3,400 pg/mL. Plasma interleukin-6, soluble tumor necrosis factor α receptor 1, and high-sensitivity C-reactive protein levels were not associated with endometriosis risk. Further research in larger studies with younger age at blood collection and longer time from blood to surgical diagnosis are required to confirm these associations. [ABSTRACT FROM AUTHOR]

Mammary tissue experiences the highest rate of proliferation during adolescence representing a period of heightened susceptibility. Few prospective studies have examined adolescent diet and breast cancer, and none have examined dietary patterns. Thus, we examined the association between adolescent dietary patterns and a diet quality index, the Alternative Healthy Eating Index (AHEI), and breast cancer in the Nurses' Health Study II among those who completed a 124-item food frequency questionnaire about their high-school diet (HS-FFQ). Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Among 45 204 women who completed the HS-FFQ, 863 cases of premenopausal breast cancer and 614 cases of postmenopausal cancer were diagnosed. A marginal inverse association was observed between the 'prudent' dietary pattern, characterized by high intake of vegetables, fruits, legumes, fish and poultry, and premenopausal breast cancer. Women in fifth quintile had a multivariable adjusted HR (95% CI) of 0.84 (0.67-1.04) for premenopausal breast cancer (Ptrend = 0.07) compared with the first quintile. Scoring higher on the AHEI was borderline significantly associated with premenopausal breast cancer with a HR of 0.81 (0.64-1.01) for the fifth quintile (Ptrend = 0.08), and this association appeared to be stronger for estrogen receptor-negative/progesterone receptor-negative tumors. No association was observed between the 'Western' pattern or the 'fast-food' pattern. Results were similar for each of these patterns when both premenopausal and postmenopausal breast cancer were considered together. An overall healthy diet during adolescence, similar to the prudent dietary pattern or adherence to the AHEI, may contribute to reducing the risk of breast cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS: We performed a comprehensive search of the PubMed/Medline and ISIWeb of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS: We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS: Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's longterm health. If these relationships are confirmed, these findings mayhave important implications in screening practices and in the management and care of endometriosis patients. [ABSTRACT FROM AUTHOR]

Study Question: Do higher leptin levels and lower adiponectin levels predict subsequent development of endometriosis?Summary Answer: Plasma leptin and adiponectin levels were not associated with laparoscopically confirmed endometriosis when collected prior to disease diagnosis.What Is Known Already: Case-control studies have identified altered levels of the inflammatory adipokines leptin and adiponectin in women with endometriosis, but it remains unclear whether inflammation results in endometriosis or whether the presence of endometriosis creates an inflammatory state.Study Design, Size, Duration: Nested, matched, case-control study within the prospective Nurses' Health Study II (NHS II) cohort. Blood samples were collected between 1996 and 1999 from 29 611 female nurses within the cohort. Women who reported endometriosis before blood collection were excluded.Participants/materials, Setting, Methods: Plasma leptin and adiponectin levels were assayed by ELISA. Three hundred and fifty cases of laparoscopically confirmed endometriosis were matched 1:2 with 694 controls of comparable race, age, infertility history, menopausal status and time of blood draw. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models adjusting for matching factors and BMI.Main Results and the Role Of Chance: After adjusting for BMI, there were no statistically significant associations between endometriosis and leptin [RR = 1.2; 95% CI = 0.7-2.0; P-value, test for linear trend (P(trend)) = 0.72], adiponectin (RR = 0.8; 95% CI = 0.5-1.2; P(trend) = 0.48) or the leptin to adiponectin ratio (RR = 0.8; 95% CI = 0.4-1.4; P(trend) = 0.14) when comparing the upper with the lower quartile. Results were unaltered when analyses were stratified by BMI or restricted to cases diagnosed ≥ 4 years after blood draw. To evaluate statistical significance and limit the role of chance to the gold standard of 5%, we present 95% CIs about the RRs, and for P-values calculated for linear tests of trend and tests of heterogeneity, we have set the α-level to be 0.05 (i.e. <0.05 is considered to be statistically significant).Limitations and Reasons For Caution: A limitation of this study is the inability to differentiate the time of endometriosis 'diagnosis' from the time of disease 'onset' due to the impossibility in identifying a precise time point at which the disease process was first initiated at a molecular or cellular level. Additional limitations include lack of information regarding stage of endometriosis and the possibility of asymptomatic disease in the control population.Wider Implications Of the Findings: The mean age at diagnosis of endometriosis in the study population is 41.7, ≈ 10 years older than the mean age of diagnosis in the general population. While this may limit the generalizability of the results, there is no reason to suspect that the association between adipokines and endometriosis risk should differ at a younger age of diagnosis in an adult population. [ABSTRACT FROM AUTHOR]

Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer. We investigated the association between body fat distribution, assessed in 1993 by self-reported waist circumference, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses’ Health Study II. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Statistical tests were two-sided. During 426 164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45 799 women. Hormone receptor status information was available for 84% of the breast cancers. The age-standardized incidence rates of breast cancer were 131 per 100 000 person-years among those in the lowest quintile of waist circumference and 136 per 100 000 person-years among those in the highest quintile. No statistically significant associations were found between waist circumference, hip circumference, or the waist to hip ratio and risk of breast cancer. However, each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)–negative breast cancer. The multivariable-adjusted hazard ratios of ER-negative breast cancer for the highest vs the lowest quintile of each body fat distribution measure were 2.75 (95% CI = 1.15 to 6.54; Ptrend = .05) for waist circumference, 2.40 (95% CI = 0.95 to 6.08; Ptrend = .26) for hip circumference, and 1.95 (95% CI = 1.10 to 3.46; Ptrend = .01) for waist to hip ratio. Our findings suggest that body fat distribution does not play an important role in the overall incidence of premenopausal breast cancer but is associated with an increased risk for ER-negative breast cancer. [ABSTRACT FROM PUBLISHER]