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Background and Aims: Little is known about how weight trajectories among women during menopausal transition and beyond may be related to risk of type 2 diabetes mellitus (T2DM). The aim of this study was to examine associations between body mass index (BMI) trajectories over 20 years, age of obesity onset, cumulative obese-years and incidence of T2DM among middle-aged women., Methods and Results: 12,302 women enrolled in the Australian Longitudinal Study on Women's Health (ALSWH) were surveyed in 1996 (Survey 1, age 45-50), 1998 and then every three years to 2016. Self-reported weight and height were collected for up to eight time points. Incident diabetes was assessed via validated self-report of physician-diagnosed diabetes. Growth mixture models were used to identify distinct BMI trajectories. A total of 1380 (11.2%) women newly developed T2DM over an average 16 years of follow-up. Seven distinct BMI trajectories were identified with differential risk of developing T2DM. Initial BMI was positively associated with T2DM risk. We also observed that risk of T2DM was positively associated with rapid weight increase, early age of obesity onset and greater obese-years., Conclusion: Slowing down weight increases, delaying the onset of obesity, or reducing cumulative exposure to obesity may substantially lower the risk of developing T2DM., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Importance: Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown., Objective: To investigate the association between body fat and breast cancer risk in women with normal BMI., Design, Setting, and Participants: This ad hoc secondary analysis of the Women's Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018., Main Outcomes and Measures: Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants., Results: Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass., Conclusions and Relevance: In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women., Trial Registration: ClinicalTrials.gov identifier: NCT00000611.

Objective: The study objective was to examine the impact of race/ethnicity on associations between anthropometric measures and diabetes risk., Research Design and Methods: A total of 136,112 postmenopausal women aged 50-79 years participating in the Women's Health Initiative without baseline cancer or diabetes were followed for 14.6 years. BMI, waist circumference (WC), and waist-to-hip ratio (WHR) were measured in all participants, and a subset of 9,695 had assessment of whole-body fat mass, whole-body percent fat, trunk fat mass, and leg fat mass by DXA. Incident diabetes was assessed via self-report. Multivariate Cox proportional hazards regression models were used to assess associations between anthropometrics and diabetes incidence., Results: During follow-up, 18,706 cases of incident diabetes were identified. BMI, WC, and WHR were all positively associated with diabetes risk in each racial and ethnic group. WC had the strongest association with risk of diabetes across all racial and ethnic groups. Compared with non-Hispanic whites, associations with WC were weaker in black women ( P < 0.0001) and stronger in Asian women ( P < 0.0001). Among women with DXA determinations, black women had a weaker association with whole-body fat ( P = 0.02) but a stronger association with trunk-to-leg fat ratio ( P = 0.03) compared with white women., Conclusions: In postmenopausal women across all racial/ethnic groups, WC was a better predictor of diabetes risk, especially for Asian women. Better anthropometric measures that reflect trunk-to-leg fat ratio may improve diabetes risk assessment for black women., (© 2018 by the American Diabetes Association.)

Background: People experience multiple co-occurring exposures to environmental pollutants, but analyses of multiple exposures have rarely been reported., Objectives: We used latent class analysis to estimate co-exposures to multiple polycyclic aromatic hydrocarbons (PAH), and tested the associations of latent classes to body mass index., Methods: We analyzed National Health and Nutrition Examination Survey (NHANES) 2013-2014 data. The sample included 2354 people aged 6-80 years. Measures included seven urinary PAH metabolites, BMI, and demographic and behavioral covariates. People were classified into mutually exclusive latent classes characterized by unique profiles of multiple PAH exposures. These classes were used as categorical independent variables in weighted multiple regression models with BMI as the dependent measure. Models were analyzed overall and by age groups (6-19, 20-59, and 60 and over.) We compared results using latent classes to results using a summed PAH exposure measure., Results: Five latent classes were identified. Two of these classes were significantly associated with higher BMI overall (p < .0001) and for the two youngest age groups. One of these classes was characterized by high multiple exposures across all PAHs, and one by moderate exposures but relatively high naphthalene and phenanthrene. The summed PAH score was associated with higher BMI only for the youngest age group., Conclusions: Persons experience multiple co-exposures to PAHs that are related to BMI and obesity across age groups. Latent class analysis provides information on higher order interactions among multiple chemicals that a summed score does not. Future work may apply this approach to other outcomes or types of co-exposures., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women's Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with <25 kg/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival., Competing Interests: The authors have declared that no competing interests exist.

Objective: The effects of BMI and physical activity on the risk of pancreatic cancer were investigated in a large population-based cohort study in Japan (JPHC study). In particular, we explored how these effects were influenced by smoking status and a history of diabetes., Methods: In total, 99,670 participants (47,499 men, and 52,171 women) were followed for an average of 11 years through the end of 2003. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated by Cox proportional hazards models., Results: A total of 224 incident cases (128 men, 96 women) of pancreatic cancer were identified. A statistically significant excess risk of pancreatic cancer was associated with current smoking (HR=1.8, CI 1.1-3.0) and a history of diabetes (HR=2.1, CI 1.3-3.5) among men. A similar increase in risk associated with current smoking (HR=2.0, CI 0.9-4.4) and diabetes (HR=1.5, CI 0.7-3.5) was also seen among women. BMI was inversely associated with risk of pancreatic cancer among men, especially among current male smokers or diabetes patients, but no association was found among women. Leisure-time physical activity was not associated with risk in either men or women., Conclusions: Our study confirms the association between cigarette smoking, history of diabetes and increased risk of pancreatic cancer. However, our data suggest that the association between BMI and risk of pancreatic cancer in this Japanese population may be different from that in Western populations.

OBJECTIVE: To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women. DESIGN: Prospective cohort study. SETTING: Forty clinical centres in the USA. PARTICIPANTS: Totally, 79 034 postmenopausal women in the Womens Health Initiative Observational Study. RESULTS: During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18-50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively. CONCLUSION: Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.

PURPOSE: The incidence of triple-negative breast cancer (TNBC) is higher in Black women compared to White women which is not explained by racial differences in body mass index (BMI). As BMI has limitations as an anthropometric measure, we used different anthropometric measures to examine associations with TNBC by race. METHOD: Of 161,808 postmenopausal participants in Womens Health Initiative, eligible were a subsample of 121,744 White and Black postmenopausal women enrolled from 1993 to 1998, 50-79 years of age with anthropometric measures who were followed for breast cancer incidence until March 2019. At entry, BMI, waist circumference (WC), and waist-hip ratio (WHR) were measured using standardized methods. Breast cancers were verified by central medical record review. Associations between anthropometric measures and triple-negative breast cancer risk were examined using Cox proportional hazards regression models. RESULTS: After 17.6 years (median) follow-up, there were 87 Black women and 529 White women with incident triple-negative breast cancer. Overall, there were no significant associations between anthropometric measures and risk of triple-negative breast cancer. However, compared to White women with normal BMI, White women with obesity (BMI ≥ 30) (HR 0.76, 95% CI 0.60, 0.96) were significantly associated with a lower risk of triple-negative breast cancer. And larger waist circumference (HR per centimeter 0.99, 95% CI 0.99, 1.00) was significantly associated with a lower risk of triple-negative breast cancer among White women. CONCLUSION: Overall, among postmenopausal women, anthropometric measures were not associated with risk of TNBC. The association among White women with larger waist circumference and women with obesity with a lower risk of triple-negative breast cancer needs further confirmation.

Obesity and obesity-related metabolic disorders, such as diabetes and chronic inflammation, have been positively associated both with postmenopausal breast cancer and with resting energy expenditure (REE). However, there is limited epidemiologic evidence on the associations between REE and risk of postmenopausal breast cancer. We used multivariable Cox proportional hazards models to examine the association between predicted REE (calculated using the Ikeda, Livingston, and Mifflin equations) and risk of postmenopausal breast cancer overall and by subtypes, and by level of body fat) among 137,283 postmenopausal women in the Women's Health Initiative (WHI). All predicted REEs were positively associated with risk of invasive breast cancer [HRq5 vs. q1 = 1.69; 95% confidence interval (CI), 1.57-1.81; HR = 1.69; 95% CI, 1.57-1.82; and HR = 1.68; 95% CI, 1.56-1.80 for Ikeda, Livingston, and Mifflin, respectively]. These positive associations were observed irrespective of the hormone receptor subtype, grade, and stage of the tumors, but were most pronounced for estrogen receptor-positive/progesterone receptor-positive tumors. After additional adjustment for body mass index (BMI), the associations were mostly attenuated and remained statistically significant for most of the outcomes. We also observed an interaction between the predicted REEs and BMI, with the associations being somewhat stronger among normal weight and overweight women than among obese women (Pinteractions < 0.05). Our findings indicate that relatively high REE is associated with increased risk of invasive breast cancer among postmenopausal women (particularly for the obesity-related tumor subtypes), irrespective of the equation used. Further studies using more objective measures of REE are, however, needed to confirm our findings.Prevention relevanceThis study showed that higher resting energy expenditure (REE) was associated with higher postmenopausal breast cancer risk. REE provides energy to support cancer-associated disorders such as obesity and inflammation. Thus, studies on its association with breast cancer can help to improve our understanding of the pathophysiology of breast cancer.

IntroductionEvidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent.MethodsA total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk.ResultsDuring a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes.ConclusionDiabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

BackgroundMost studies demonstrating an association between excess adiposity and postmenopausal breast cancer have used anthropometric measures, particularly body mass index (BMI). However, more direct body fat measures may more accurately determine the relationship between body fat distribution and breast cancer risk.MethodsCox proportional hazards regression models were created to examine the associations of dual-energy x-ray absorptiometry (DXA) body fat measures (at baseline and during follow-up) with breast cancer risk among 10 931 postmenopausal women from the Women's Health Initiative cohort. A total of 639 incident invasive breast cancer cases (including 484 estrogen receptor positive (ER+) cases) were ascertained after a median follow-up of 15.0 years.ResultsExcess whole body fat mass and trunk fat mass were positively associated with risk invasive breast cancer risk. These associations persisted even after additional adjustment for standard anthropometric measures. In time-dependent analyses, we observed that both whole body fat mass and trunk fat mass, in the highest versus lowest category, were associated with a doubling of risk of invasive breast cancer overall (HR: 2.17; 95% CI: 1.54-3.05 and 2.20; 1.55-3.14, respectively) and of ER+ breast cancer (2.05; 1.37-3.05 and 2.03; 1.34-3.07, respectively). The remaining DXA measures were also positively associated with breast cancer risk in baseline and time-dependent analyses.ConclusionThese findings suggest that DXA-derived body fat measures are positively associated with breast cancer risk after adjustment for BMI and other conventional breast cancer risk factors.

BackgroundObesity is a strong risk factor for endometrial cancer, but it is unclear whether metabolic syndrome (MetS) contributes to endometrial cancer risk over and above the contribution of obesity.MethodsWe examined the association of MetS and its components with risk of endometrial cancer in a sub-cohort of 24,210 women enrolled in the Women's Health Initiative cohort study. Two variants of the National Cholesterol Education Program Adult Treatment Panel III definition of the MetS were used: one including and one excluding waist circumference (WC). Cox proportional hazards models were used to estimate the association of the study exposures with disease risk.ResultsWhen WC was included in the definition, MetS showed an approximately two-fold increase in endometrial cancer risk (HR 2.20; 95% CI 1.61-3.02); however, when WC was excluded, MetS was no longer associated with risk. We also observed that women with hyperglycemia, dyslipidemia and hypertension, in combination, had almost a twofold increased risk of endometrial cancer, independent of WC (HR 1.94; 95% CI 1.09, 3.46). Glucose, and, in particular, WC and body mass index were also positively associated with risk.ConclusionsOur findings suggest that MetS may predict risk of endometrial cancer independent of obesity among women with the remaining four Mets components.

ObjectiveWeight gain frequently occurs after smoking cessation. The objective of this study was to examine whether weight gain after smoking cessation was attenuated by physical activity (PA) in postmenopausal women.MethodsA total of 4,717 baseline smokers from the Women's Health Initiative were followed for 3 years. One thousand two hundred eighty-two women quit smoking, and 3,435 continued smoking. Weight was measured at baseline and at the year 3 visit. PA was assessed at both times by self-report, summarized as metabolic equivalent task-hours per week. Multiple linear regression models were used to assess the association between PA and postcessation weight gain, adjusting for potential confounding factors.ResultsCompared with continuing smokers, quitters gained an average of 3.5 kg (SD = 5.6) between the baseline and year 3 visit. Quitters with decreased PA had the highest amount of weight gain (3.88 kg, 95% CI: 3.22-4.54); quitters with increased PA (≥15 metabolic equivalent task-hours /week) had the lowest weight gain (2.55 kg, 95% CI: 1.59-3.52). Increased PA had a stronger beneficial association for postcessation weight gain for women with obesity compared to normal weight women. Quitters who had low PA at baseline and high PA at year 3 and were also enrolled in a dietary modification intervention had nonsignificant weight gain (1.88 kg, 95% CI: -0.21-3.96) compared with continuing smokers.ConclusionsOur data demonstrate that even a modest increase in PA (equivalent to current recommendations) can attenuate weight gain after quitting smoking among postmenopausal women, especially in combination with improved diet.

Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-

Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women's Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER+/PR+, and HER2+ breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACRSee related editorial by Friedenreich and McTiernan, p. 313.

Background: Studies on the association between vegetarian diets and nonalcoholic fatty liver disease (NAFLD) are limited and have inconsistent results. This study aims to explore the association between vegetarian diets and NAFLD and compare the stage of fibrosis between vegetarians and nonvegetarians in a US representative sample. Methods: Cross‐sectional data from 23,130 participants aged ≥20 years were obtained from the National Health and Nutrition Examination Survey, 2005–2018. Vegetarian status was classified based on two 24‐h dietary recalls. We examined the association between vegetarian diets and the risk of NAFLD using the propensity score weighting method. Results: Vegetarian diets were significantly associated with decreases in hepatic steatosis index (HSI), US fatty liver index and nonalcoholic fatty liver disease fibrosis score with mean differences of −2.70 (95% confidence interval [CI]: −3.69, −1.70), −3.03 (95% CI: −7.15, −0.91) and −0.12 (95% CI: −0.26, −0.01), respectively. While modelling the risk of NAFLD, we estimated that vegetarians were 53% less likely to have NAFLD assessed by HSI (odds ratios [OR]: 0.47; 95% CI: 0.34, 0.65). The effect of vegetarian diets was higher among individuals with lower waist circumferences (OR: 0.20) than among those with higher waist circumferences (OR: 0.53, pinteraction ${p}_{\text{interaction}}\,$= 0.004). However, the association was largely attenuated after adjusting for body mass index and diabetes status. No significant association was identified between vegetarian diets and advanced fibrosis. Conclusions: Vegetarian diets were associated with a lower prevalence of NAFLD among US adults, and the association appeared to be stronger in people with lower waist circumferences. Further studies are warranted to replicate our findings. Key points: Vegetarians had low risks of nonalcoholic fatty liver disease (NAFLD) development.A stronger association was observed among people with lower waist circumferences.Vegetarians were observed to have lower degrees of fibrosis among people with NAFLD.Future nutritional interventions may prioritise a low‐inflammatory dietary plan. [ABSTRACT FROM AUTHOR]

Background Associations of weight changes and intentionality of weight loss with longevity are not well described. Methods Using longitudinal data from the Women's Health Initiative (N  = 54 437; 61–81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3. Results A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64–0.71), 95 (OR, 0.65; 95% CI, 0.60–0.71), and 100 (OR, 0.62; 95% CI, 0.49–0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74–0.94 and OR, 0.49; 95% CI, 0.44–0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses. Conclusions Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women's Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women. [ABSTRACT FROM AUTHOR]

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four‐time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self‐reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer. What's new? Higher birthweight is associated with increased risk of breast cancer, especially in premenopausal women. In this study, the authors analyzed the effect of adult weight and height on the association between birthweight and postmenopausal breast cancer. They enrolled 70,397 postmenopausal women and monitored their breast cancer incidence over a 25‐year follow up. Women under 6 pounds at birth had reduced cancer risk, but more than 40% of this effect was mediated by adult height. High birthweight was not associated with postmenopausal breast cancer risk. Adult weight gain was associated with increased risk, regardless of birthweight. [ABSTRACT FROM AUTHOR]

Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking.Methods: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up.Results: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years.Conclusions: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the extent of error present in self-reported weight data in the Women's Health Initiative, variables that may be associated with error, and to develop methods to reduce any identified error.Design: Prospective cohort study.Setting: Forty clinical centres in the USA.ParticipantsWomen (n 75 336) participating in the Women's Health Initiative Observational Study (WHI-OS) and women (n 6236) participating in the WHI Long Life Study (LLS) with self-reported and measured weight collected about 20 years later (2013-2014).Results: The correlation between self-reported and measured weights was 0·97. On average, women under-reported their weight by about 2 lb (0·91 kg). The discrepancies varied by age, race/ethnicity, education and BMI. Compared with normal-weight women, underweight women over-reported their weight by 3·86 lb (1·75 kg) and obese women under-reported their weight by 4·18 lb (1·90 kg) on average. The higher the degree of excess weight, the greater the under-reporting of weight. Adjusting self-reported weight for an individual's age, race/ethnicity and education yielded an identical average weight to that measured.Conclusions: Correlations between self-reported and measured weights in the WHI are high. Discrepancies varied by different sociodemographic characteristics, especially an individual's BMI. Correction of self-reported weight for individual characteristics could improve the accuracy of assessment of obesity status in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to examine the impact of race/ethnicity on associations between anthropometric measures and diabetes risk.Research Design and Methods: A total of 136,112 postmenopausal women aged 50-79 years participating in the Women's Health Initiative without baseline cancer or diabetes were followed for 14.6 years. BMI, waist circumference (WC), and waist-to-hip ratio (WHR) were measured in all participants, and a subset of 9,695 had assessment of whole-body fat mass, whole-body percent fat, trunk fat mass, and leg fat mass by DXA. Incident diabetes was assessed via self-report. Multivariate Cox proportional hazards regression models were used to assess associations between anthropometrics and diabetes incidence.Results: During follow-up, 18,706 cases of incident diabetes were identified. BMI, WC, and WHR were all positively associated with diabetes risk in each racial and ethnic group. WC had the strongest association with risk of diabetes across all racial and ethnic groups. Compared with non-Hispanic whites, associations with WC were weaker in black women (P < 0.0001) and stronger in Asian women (P < 0.0001). Among women with DXA determinations, black women had a weaker association with whole-body fat (P = 0.02) but a stronger association with trunk-to-leg fat ratio (P = 0.03) compared with white women.Conclusions: In postmenopausal women across all racial/ethnic groups, WC was a better predictor of diabetes risk, especially for Asian women. Better anthropometric measures that reflect trunk-to-leg fat ratio may improve diabetes risk assessment for black women. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To examine how routine laboratory biomarkers and clinical parameters available within medical records related to overall survival in patients with non-small cell lung cancer (NSCLC).Design: Retrospective chart review.Setting: University-based cancer center in rural West Virginia.Sample: 110 patients from the U.S. Appalachian region with a primary diagnosis of NSCLC at initial hospitalization.Methods: Electronic medical records were reviewed for one year after discharge or until death. The Kaplan-Meier method was used to compare survival curves for each prognostic factor. Cox proportional hazards model was used for multivariate analyses.Main Research Variables: Total white blood cell, neutrophil, lymphocyte, and platelet counts; hemoglobin level; body mass index (BMI); performance status; and cancer stage.Findings: Low BMI (lower than 18.5 lb/in2), advanced cancer stage (IIIB or IV), and elevated neutrophil (higher than 8 x 103/mcl) and platelet (300-826 x 1012/L) counts were significant, independent prognostic factors for shorter survival time in NSCLC. BMI (hazard ratio [HR] = 2.15, 95% confidence interval [CI] [0.94, 4.9]) and neutrophil (HR = 2.93, 95% CI [1.53, 5.59]) and platelet (HR = 2.65, 95% CI [1.25, 5.62]) counts were overall prognostic predictors for patients with advanced NSCLC and remained in the multivariate survival model.Conclusions: This study detected two known clinical parameters, cancer stage and nutritional status (i.e., BMI and neutrophil and platelet counts), as having independent prognostic significance for shorter survival in NSCLC. Research on survival in patients with NSCLC should include those identified laboratory biomarkers and clinical parameters for screening patients at risk for shorter survival time following hospitalization. Investigation of whether treatments tailored to address neutrophil and platelet counts and BMI can improve survival outcomes also is warranted.Implications for Nursing: Attention to common biomarkers recorded in patient charts (e.g., neutrophil and platelet counts) as well as BMI could allow nurses to identify patients at risk for low survival. Interventions should be identified and initiated. Longitudinal studies in clinical settings that follow the survival of patients with NSCLC are essential. [ABSTRACT FROM AUTHOR]

Obesity is a well-established risk factor for postmenopausal breast cancer. Recent studies suggest that smoking increases the risk of breast cancer. However, the effect of co-occurrence of smoking and obesity on breast cancer risk remains unclear. A total of 76,628 women aged 50–79 years enrolled in the Women's Health Initiative Observational Study were followed through August 14, 2009. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. Over an average 10.3 years of follow-up, 3,378 incident cases of invasive breast cancer were identified. The effect of smoking on the risk of developing invasive breast cancer was modified significantly by obesity status among postmenopausal women, regardless of whether the obesity status was defined by body mass index (Pinteraction = 0.01) or waist circumference (Pinteraction = 0.02). A significant association between smoking and breast cancer risk was noted in nonobese women (hazard ratio = 1.25, 95% confidence interval: 1.05, 1.47) but not in obese women (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). In conclusion, this study suggests that the effect of smoking exposure on breast cancer risk was modified by obesity among postmenopausal women. The modification effect did not differ by general versus abdominal obesity. [ABSTRACT FROM PUBLISHER]

Purpose: Personality traits have been reported to be associated with type 2 diabetes (T2DM) risk. The objective of this study was to examine whether and to what extent the associations between personality traits (dispositional optimism, hostility, and negative emotional expressiveness) and risk of T2DM were mediated by health behaviors and obesity.Methods: Postmenopausal women (n = 110,992) aged 50-79 years without diabetes at enrollment in the Women's Health Initiative study (1993-1998) were followed up to 25 years. Incident diabetes was assessed via a validated self-report of physician-diagnosed diabetes treated with insulin or other hypoglycemic medications. Mediation analyses were performed using approaches under a counterfactual framework.Results: An inverse association of optimism with diabetes was significantly mediated by a factor primarily extracted from physical activity, diet quality, and sleep quality with a mediated proportion of 28%. Positive associations for hostility and negative emotional expressiveness were substantially mediated by a factor primarily composed of body mass index and waist circumference with mediated proportions of 32% and 44%, respectively.Conclusions: Our data revealed that less than half of the associations between personality traits and risk of T2DM were explained by indirect health behavior pathways. Women's personality traits should be considered in prevention of diabetes in addition to promoting health behaviors. [ABSTRACT FROM AUTHOR]

Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders.Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI).Methods: A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI.Results: In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β = 0.092; 95% CI 0.026, 0.158) and IL-6 (β = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β = -0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (β = -0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels.Conclusions: Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI. [ABSTRACT FROM AUTHOR]