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Investigators in several epidemiologic studies have observed an inverse association between body mass index (BMI) and lung cancer risk, while others have not. The authors used data from the Women's Health Initiative to study the association of anthropometric factors with lung cancer risk. Over 8 years of follow-up (1998-2006), 1,365 incident lung cancer cases were ascertained among 161,809 women. Cox proportional hazards models were used to estimate hazard ratios adjusted for covariates. Baseline BMI was inversely associated with lung cancer in current smokers (highest quintile vs. lowest: hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.42, 0.92). When BMI and waist circumference were mutually adjusted, BMI was inversely associated with lung cancer risk in both current smokers and former smokers (HR = 0.40 (95% CI: 0.22, 0.72) and HR = 0.61 (95% CI: 0.40, 0.94), respectively), and waist circumference was positively associated with risk (HR = 1.56 (95% CI: 0.91, 2.69) and HR = 1.50 (95% CI: 0.98, 2.31), respectively). In never smokers, height showed a borderline positive association with lung cancer. These findings suggest that in smokers, BMI is inversely associated with lung cancer risk and that waist circumference is positively associated with risk. [ABSTRACT FROM AUTHOR]

Flavonoids are found in a variety of foods and have anticarcinogenic properties in experimental models. Few epidemiologic studies have examined whether flavonoid intake is associated with breast cancer in humans. In this study, the authors investigated whether dietary flavonoid intake was associated with reduced risk of breast cancer in a population-based sample of US women. They conducted a case-control study among women who resided in Nassau and Suffolk counties on Long Island, New York. Cases and controls were interviewed about known and suspected risk factors and asked to complete a food frequency questionnaire regarding their average intake in the prior 12 months. A total of 1,434 breast cancer cases and 1,440 controls provided adequate responses. A decrease in breast cancer risk was associated with flavonoid intake; the decrease was most pronounced among postmenopausal women for flavonols (odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.40, 0.73), flavones (OR = 0.61, 95% CI: 0.45, 0.83), flavan-3-ols (OR = 0.74, 95% CI: 0.55, 0.99), and lignans (OR = 0.69, 95% CI: 0.51, 0.94). The authors conclude that intake of flavonols, flavones, flavan-3-ols, and lignans is associated with reduced risk of incident postmenopausal breast cancer among Long Island women. These results suggest that US women can consume sufficient levels of flavonoids to benefit from their potential chemopreventive effects. [ABSTRACT FROM AUTHOR]

Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological studies conducted to evaluate this hypothesis have not assessed all flavonoids, including classes that could contribute to intake among Americans, which would result in an underestimation of intake. This misclassification could mask variability among individuals, resulting in attenuated effect estimates for the association between flavonoids and cancer. To augment flavonoid and lignan intake estimates, we developed a database that can be used in conjunction with a food-frequency questionnaire (FFQ). Coupling information derived from the available literature with the U.S. Department of Agriculture databases, we estimated content of 6 flavonoid classes and lignans for 50 food group items. We combined these estimates with responses from a modified Block FFQ that was self-completed in 1996-1997 by a population-based sample of women without breast cancer on Long Island, New York (n = 1,500). Total flavonoid and lignan content of food items ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and grapefruit. Individual intake estimates, from highest to lowest, were flavan-3-ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones. Each class of flavonoids and lignans exhibited a wide range of intake levels. This database is useful to quantify flavonoid and lignan intake for other observational studies conducted in the United States that utilize the Block FFQ. [ABSTRACT FROM AUTHOR]

Understanding risk perceptions for breast cancer among women smokers is important because smokers tend to underutilize breast cancer screening. Perceptions of the relative importance of a variety of factors which may increase breast cancer risk and the benefits/barriers of mammography, were examined among women who were current (n = 185), ex- (n = 632) and never (n = 623) smokers. Participants were a subset of women taking part in a project to increase mammography utilization among women aged 50 and over. Current smokers, but not ex-smokers, were significantly less likely than never smokers to agree that health risk behaviors most frequently seen in smokers (e.g., smoking cigarettes, high-fat diet, low intake of fruits and vegetables, physical inactivity, drinking alcohol) may increase risk for breast cancer. Current smokers, but not ex-smokers, perceived more barriers and fewer benefits of mammography, than never smokers. [ABSTRACT FROM AUTHOR]

Purpose: A recent meta-analysis of five case-control studies and one cohort study reported that exposure to glyphosate was associated with increased risk of non-Hodgkin's lymphoma (NHL). The meta-analysis was based on estimates of risk from the included studies at the highest reported exposure level obtained from analyses with the longest lag period. The extent to which the summary estimate depends upon the exposure definitions and assumed latency period is uncertain., Methods: We carried out sensitivity analyses to determine how the definition of exposure and the choice of latency period affect the summary estimate from meta-analyses of the 6 studies included in the recent meta-analysis. We also conducted a meta-analysis of ever-exposure to glyphosate incorporating the most updated results from the case-control studies., Results: The summary estimates of risk varied considerably depending on both the assumptions about exposure level and latency. Using the highest reported exposure levels, evidence of an association between glyphosate and NHL was strongest when estimates from analyses in the cohort study with a 20-year lag [RR = 1.41 (95% CI 1.13-1.76)] and a 15-year lag [RR = 1.25 (95% CI 1.01-1.25)] were included. In our meta-analysis of ever-exposure with no lag period, the summary relative risk with updated estimates was 1.05 (95% CI 0.87-1.28)., Conclusion: The results of meta-analyses of glyphosate exposure and NHL risk depend on assumptions made about both exposure level and latency period. Our results for ever-exposure are consistent with those of two recent meta-analyses conducted using somewhat different study inclusion criteria.

Background: Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE 1 ) and 16-hydroxyestrone (16-OHE 1 ) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer., Methods: This population-based study was initiated in 1996-1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE 1 and 16-OHE 1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided., Results: Urinary concentrations of the 2-OHE 1 to 16-OHE 1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; P interaction = .008)., Conclusions: The urinary 2-OHE 1 to 16-OHE 1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Obesity 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., Methods: We 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., Results: When 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., Conclusions: Our findings suggest that MetS may predict risk of endometrial cancer independent of obesity among women with the remaining four Mets components.

Purpose: The purpose of this study was to examine the association of type II diabetes and anthropometric variables with risk of pancreatic cancer among postmenopausal women., Methods: Weight, height, waist circumference, and hip circumference were measured by trained personnel, whereas history of diabetes and weight earlier in life were self-reported. Pancreatic cancer was ascertained via central review of medical records by physician adjudicators. After exclusions, 1045 cases of pancreatic cancer were diagnosed among 156,218 women over a median follow-up of approximately 18 years. Cox proportional hazards models were used to estimate the associations of study factors with pancreatic cancer risk., Results: Diabetes (hazards ratio (HR): 1.30; 95% confidence intervals (95% CI): 1.01-1.66), and in particular, waist circumference, waist-to-hip ratio, and waist-to-height ratio showed positive associations with pancreatic cancer risk (HRs for highest vs. lowest level 1.38; 95% CI: 1.14-1.66, 1.40; 1.17-1.68; and 1.36; 1.13-1.64, respectively). Body mass index at the baseline showed only a borderline positive association with risk (HR: 1.21; 95% CI: 0.97-1.51). Body mass index at age 50 years, but not at ages 18 and 35 years, was also associated with increased pancreatic cancer risk., Conclusions: In this study of postmenopausal women, central adiposity and, to a lesser extent, general adiposity and a history of diabetes, were associated with increased pancreatic cancer risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/objective: Many studies have shown a U-shaped association of sleep duration with mortality; however, this association is difficult to interpret owing to possible reverse causation, residual confounding, and measurement issues. We used data from the Women's Health Initiative to examine the associations of sleep duration, insomnia, and use of sleep aids with death from cardiovascular disease (CVD), cancer, "other" causes, and all causes combined., Methods: Cox proportional hazards models were used in the analysis of baseline data and in time-dependent analyses of repeated measures to estimate associations of sleep-related factors with mortality. Among 158,203 women with information regarding sleep, 30,400 total deaths, 8857 CVD deaths, 9284 cancer deaths, and 11,928 other deaths were ascertained over a median of 17.8 years., Results: In both baseline and time-dependent analyses, both short (≤5 h) and long sleep (≥9 h) durations were associated with increased risk of total, CVD, and "other" deaths, but not with cancer deaths. Insomnia showed no association with mortality, whereas use of sleep medications was associated with an increased mortality risk., Conclusions: While our findings showed a small but robust association of sleep duration with mortality in postmenopausal women, studies including objective measurements of sleep quality and efficiency are needed to clarify these associations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Obesity is a chronic inflammatory condition strongly associated with the risk of numerous cancers. We examined the association between circulating high-sensitivity C-reactive protein (hsCRP), a biomarker of inflammation and strong correlate of obesity, and the risk of three understudied obesity-related cancers in postmenopausal women: ovarian cancer, kidney cancer, and multiple myeloma., Methods: Participants were 24,205 postmenopausal women who had measurements of baseline serum hsCRP (mg/L) in the Women's Health Initiative (WHI) CVD Biomarkers Cohort, a collection of four sub-studies within the WHI. Incident cancers were identified over 17.9 years of follow-up (n = 153 ovarian, n = 110 kidney, n = 137 multiple myeloma). hsCRP was categorized into study-specific quartiles. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of baseline hsCRP with the risk of these cancers., Results: There was no clear association between baseline hsCRP concentration and the risk of ovarian cancer (quartile 4 vs. 1: HR 0.87, 95% CI 0.56-1.37), kidney cancer (HR 0.95, 95% CI 0.56-1.61), or multiple myeloma (HR 0.82, 95% CI 0.52-1.29). HRs for 1 mg/L increases in hsCRP also approximated the null value for each cancer., Conclusions: The results of this study suggest that elevated CRP is not a major risk factor for these obesity-related cancers (ovarian or kidney cancers, or multiple myeloma) among postmenopausal women. Given the importance of elucidating the mechanisms underlying the association of obesity with cancer risk, further analysis with expanded biomarkers and in larger or pooled prospective cohorts is warranted.

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-<25.0, 25.0-<30.0 and ≥30.0 kg/m 2 ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis., (© 2018 UICC.)

Background: Little is known about risk factors for adult glioma. Adiposity has received some attention as a possible risk factor., Methods: We examined the association of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR), measured at enrollment, as well as self-reported weight earlier in life, with risk of glioma in a large cohort of postmenopausal women. Over 18 years of follow-up, 217 glioma cases were ascertained, including 164 glioblastomas. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals., Results: There was a modest, non-significant trend toward increasing risk of glioma and glioblastoma with increasing measured BMI and WHR. No trend was seen for WC. Self-reported BMI earlier in life showed no association with risk., Conclusions: Our weak findings regarding the association of adiposity measures with risk of glioma are in agreement the results of several large cohort studies. In view of the available evidence, adiposity is unlikely to represent an important risk factor for glioma., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Limited evidence suggests that hyperinsulinemia may contribute to the risk of breast, endometrial, and, possibly, ovarian cancer. The aim of this study was to assess the association of serum glucose and insulin with risk of these cancers in postmenopausal women, while taking into account potential confounding and modifying factors. We studied 21 103 women with fasting baseline insulin and glucose measurements in a subsample of the Women's Health Initiative. The subsample was composed of four studies within Women's Health Initiative with different selection and sampling strategies. Over a mean of 14.7 years of follow-up, 1185 breast cancer cases, 156 endometrial cancer cases, and 130 ovarian cancer cases were diagnosed. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) by quartile of glucose or insulin. Serum insulin was positively associated with breast cancer risk (multivariable-adjusted HR for highest vs. lowest quartile 1.41, 95% CI: 1.16-1.72, Ptrend<0.0003), and glucose and insulin were associated with roughly a doubling of endometrial cancer risk (for glucose: HR: 2.00, 95% CI: 1.203.35, Ptrend=0.01; for insulin: HR: 2.39, 95% CI: 1.32-4.33, Ptrend=0.008). These associations remained unchanged or were slightly attenuated after mutual adjustment, adjustment for serum lipids, and assessment of possible reverse causation. Glucose and insulin showed no association with ovarian cancer. Our findings provide support for a role of insulin-related pathways in the etiology of cancers of the breast and endometrium. However, because of the unrepresentative nature of the sample, our results need confirmation in other populations.

Purpose: Obesity, which is commonly accompanied by dyslipidemia, is associated with an increased risk of certain cancers. However, the association of serum lipids with specific obesity-related cancers is unclear., Methods: We examined the association of baseline lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) with risk of developing seven obesity-related cancers in a subcohort of 24,208 participants in the Women's Health Initiative. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of lipids with cancers of the breast, colorectum, pancreas, endometrium, ovary, and kidney, and multiple myeloma., Results: Total cholesterol and LDL-C showed no association with these outcomes. HDL-C was inversely associated, and triglycerides were positively associated, with several cancers. However, after adjustment for other lipids or insulin, consideration of preclinical disease, and exclusion of women taking statins, most associations were attenuated and no longer significant. Only the inverse association of HDL-C with pancreatic cancer (HR for highest vs. lowest quartile 0.52, 95% CI 0.32-0.85, p for trend 0.007) and the positive association of triglycerides with kidney cancer (HR for highest vs. lowest quartile 3.21, 95% CI 1.63-6.33, p for trend = 0.0001) remained significant. However, the inverse association of HDL-C with pancreatic cancer was no longer significant when women who lost substantial weight before diagnosis were excluded., Conclusions: Our results suggest that when possible sources of confounding and bias are taken into account there are few robust associations of lipids with obesity-related cancers.

Background: Obesity and the metabolic syndrome (MetS) have both been linked to increased risk of postmenopausal breast cancer; however, their relative contributions are poorly understood. Methods: We examined the association of metabolic phenotypes of obesity defined by presence of the MetS (yes and no) and body mass index (BMI; normal, overweight, obese) with risk of postmenopausal breast cancer in a prospective analysis of a cohort of postmenopausal women ( n ∼ 21,000) with baseline measurements of blood glucose, triglycerides, HDL-cholesterol, blood pressure, waist circumference, and BMI. Women were classified into 6 metabolic obesity phenotypes according to their BMI (18.5-<25.0, 25.0-<30.0, ≥30.0 kg/m 2 ) and presence of the MetS (≥3 of the following: waist circumference ≥88 cm, triglycerides ≥150 mg/dL, HDL-C <50 mg/dL, glucose ≥100 mg/dL, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension). HRs for incident breast cancer and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models. Results: Over 15 years of follow-up, 1,176 cases of invasive breast cancer were diagnosed. Obesity, regardless of metabolic health, was associated with increased risk of breast cancer. Being obese and metabolically unhealthy was associated with the highest risk: HR, 1.62; 95% CI, 1.33-1.96. These associations were stronger in women who had never used hormone therapy. Conclusions: Our findings suggest that both obesity and metabolic dysregulation are associated with breast cancer risk. Impact: Beyond BMI, metabolic health should be considered a clinically relevant and modifiable risk factor for breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1730-5. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Compared to non-Hispanic whites, African-American women tend to be diagnosed with breast cancer at an earlier age, to have less favorable tumor characteristics, and to have poorer outcomes from breast cancer. The extent to which differences in clinical characteristics account for the black/white disparity in breast cancer mortality is unclear. The purpose of this investigation was to examine the association of clinical, demographic, and treatment variables with total mortality and breast cancer recurrence by race/ethnicity in a cohort of women diagnosed with invasive breast cancer., Methods: To this end, we used data on 3890 invasive breast cancer cases diagnosed at a single medical center. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association of tumor characteristics and treatment variables with mortality and recurrence., Results: Compared to white women, black women with breast cancer presented with tumors that had worse prognostic factors, particularly higher stage, lower frequency of hormone-receptor positive tumors, and higher frequency of comorbidities. Hispanics also generally had less favorable prognostic factors compared to non-Hispanic whites. Among estrogen receptor-positive cases, blacks had roughly a two-fold increased risk of recurrence compared to non-Hispanic whites. However, ethnicity/race was not associated with total mortality. Tumor stage, tumor size, and Charlson comorbidity index were positively associated with mortality, and mammography and chemotherapy and hormone therapy were inversely associated with mortality., Conclusion: In spite of poorer prognostic factors among blacks compared whites, race/ethnicity was not associated with total mortality in our study.

Introduction: The epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women., Methods: We used data from the Women's Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest., Results: Being parous vs. nulliparous was associated with reduced risk (HR=0.84, 95% CI 0.70-1.00), and women who had 1-2 and 3-4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20-29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00-1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk., Conclusions: Together with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

White blood cell (WBC) count appears to predict total mortality and coronary heart disease (CHD) mortality, but it is unclear to what extent the association reflects confounding by smoking, underlying illness, or comorbid conditions. We used data from the Women's Health Initiative to examine the associations of WBC count with total mortality, CHD mortality, and cancer mortality. WBC count was measured at baseline in 160,117 postmenopausal women and again in year 3 in 74,375 participants. Participants were followed for a mean of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline WBC count and of the mean of baseline + year 3 WBC count. High deciles of both baseline and mean WBC count were positively associated with total mortality and CHD mortality, whereas the association with cancer mortality was weaker. The association of WBC count with mortality was independent of smoking and did not appear to be influenced by previous disease history. The potential clinical utility of this common laboratory test in predicting mortality risk warrants further study., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We used data from the Women's Health Initiative to examine the association of platelet count with total mortality, coronary heart disease (CHD) mortality, cancer mortality, and non-CHD/noncancer mortality., Methods: Platelet count was measured at baseline in 159,746 postmenopausal women and again in year 3 in 75,339 participants. Participants were followed for a median of 15.9 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline platelet count and of the mean of baseline + year 3 platelet count., Results: Low and high deciles of both baseline and mean platelet count were positively associated with total mortality, CHD mortality, cancer mortality, and non-CHD/noncancer mortality. The association was robust and was not affected by adjustment for a number of potential confounding factors, exclusion of women with comorbidity, or allowance for reverse causality. Low- and high-platelet counts were associated with all four outcomes in never smokers, former smokers, and current smokers., Conclusions: In this large study of postmenopausal women, both low- and high-platelet counts were associated with total and cause-specific mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The inter-relationships between smoking habits and weight gain are complex. However, few studies have examined the association of smoking habits with weight gain over the life course., Methods: Major smoking parameters and weight gain over time were examined in a large cohort of postmenopausal women aged 50-79 years at enrollment between 1993 and 1998 (N=161,808) and followed through 2014 (analyses conducted in 2016). Cross-sectional analyses were used to assess the association of smoking and body weight at baseline. Retrospective data were used to correlate smoking status with body weight over a 45-year period prior to enrollment. In addition, the association of smoking with weight gain over 6 years of follow-up was examined., Results: At baseline, women who had quit smoking prior to enrollment weighed 4.7 kg more than current smokers and 2.6 kg more than never smokers. Former, never, and current smokers all gained weight over the 45-year period from age 18 years to time of enrollment (average age, 63 years): 16.8, 16.4, and 14.6 kg, respectively. In prospective analyses, women who were current smokers at baseline but who quit smoking during follow-up gained more than 5 kg by Year 6 compared with current smokers at baseline who continued to smoke. Among long-term quitters, greater intensity of smoking and more recent quitting were associated with greater weight gain., Conclusions: These results suggest that excess weight gain associated with smoking cessation occurs soon after quitting and is modest relative to weight gain in never smokers over the adult lifespan., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The possibility that a subset of persons who are obese may be metabolically healthy-referred to as the 'metabolically healthy obese' (MHO) phenotype-has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS)., Methods: We used repeated measurements available for a subcohort of participants enrolled in the Women's Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5-<25.0, 25.0-<30.0, ⩾30.0 kg m -2 ) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another., Results: Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of 'regressing' to the metabolically healthy normal-weight phenotype was 52%., Conclusions: The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: The relationship between obesity and circulating levels of antioxidants is poorly understood. Most studies that have examined the association of adiposity with blood or tissue concentrations of antioxidant micronutrients have been cross-sectional, and few have compared the associations for indices of overall obesity and central obesity. Our aim was to prospectively examine the longitudinal association of body mass index (BMI), waist circumference (WC), waist circumference-height ratio (WCHtR) and waist-hip ratio (WHR) with major serum antioxidants in a population of postmenopausal women., Subjects/methods: We used a subsample of participants in the Women's Health Initiative aged 50-79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (N=2672). Blood samples were used to measure α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, α-tocopherol, γ-tocopherol and retinol at baseline, and at years 1, 3 and 6. We used mixed-effects linear regression analyses to examine associations between anthropometric measures and serum antioxidants at baseline and over time, controlling for covariates., Results: In longitudinal analyses, carotenoids, and particularly β-carotene, were strongly and inversely associated with BMI, WC and WCHtR and less so with WHR. α-Tocopherol showed a strong positive association with WHR but not with other anthropometric measures, whereas γ-tocopherol was positively and strongly associated with BMI, WC, WCHtR and less so with WHR. Retinol was positively associated with WHR. The inverse association of several carotenoids with anthropometric measures was stronger in never and former smokers compared with current smokers and in women without the metabolic syndrome. The inverse association of carotenoids with obesity measures may reflect reduced micronutrient concentrations owing to inflammation associated with obesity., Conclusions: In the present study, the strongest observed associations between anthropometric variables and micronutrients were an inverse association of WC with serum β-carotene and a positive association of WC with γ-tocopherol.

Background: Several health agencies have issued guidelines promoting behaviors to reduce chronic disease risk; however, little is known about the impact of such guidelines, particularly on cancer incidence., Objective: The objective was to determine whether greater adherence to the American Cancer Society (ACS) cancer prevention guidelines is associated with a reduction in cancer incidence, cancer mortality, and total mortality., Design: The NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults aged 50-71 y at recruitment in 1995-1996, was followed for a median of 10.5 y for cancer incidence, 12.6 y for cancer mortality, and 13.6 y for total mortality. Participants who reported a history of cancer or who had missing data were excluded, yielding 476,396 subjects for analysis. We constructed a 5-level score measuring adherence to ACS guidelines, which included baseline body mass index, physical activity, alcohol intake, and several aspects of diet. Cox proportional hazards models were used to compute HRs and 95% CIs for the association of the adherence score with cancer incidence, cancer mortality, and total mortality. All analyses included fine adjustment for cigarette smoking., Results: Among 476,396 participants, 73,784 incident first cancers, 16,193 cancer deaths, and 81,433 deaths from all causes were identified in the cohort. Adherence to ACS guidelines was associated with reduced risk of all cancers combined: HRs (95% CIs) for the highest compared with the lowest level of adherence were 0.90 (0.87, 0.93) in men and 0.81 (0.77, 0.84) in women. Fourteen of 25 specific cancer sites showed a reduction in risk associated with increased adherence. Adherence was also associated with reduced cancer mortality [HRs (95% CIs) were 0.75 (0.70, 0.80) in men and 0.76 (0.70, 0.83) in women] and reduced all-cause mortality [HRs (95% CIs) were 0.74 (0.72, 0.76) in men and 0.67 (0.65, 0.70) in women]., Conclusions: In both men and women, adherence to the ACS guidelines was associated with reductions in all-cancer incidence and the incidence of cancer at specific sites, as well as with reductions in cancer mortality and total mortality. These data suggest that, after accounting for cigarette smoking, adherence to a set of healthy behaviors may have considerable health benefits., (© 2015 American Society for Nutrition.)

Background: Obesity is a risk factor for several cancers in postmenopausal women. We attempted to determine cutoffs of adiposity measures in relation to risk of obesity-related cancers among postmenopausal women and to examine the effects of hormone therapy (HT) use on the cutoffs, neither of which has been broadly studied., Methods: We used data from the Women's Health Initiative cohort (n=144,701) and applied Cox-proportional hazards regressions to each combination of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI], weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist to height ratio). Interactions between the anthropometric measures and HT use were also examined. Cutoffs were determined by applying a grid search followed by a two-fold cross validation method. Survival ROC analysis of 5- and 10-year incidence followed., Results: Breast, colorectal, colon, endometrium, kidney, and all cancers combined were significantly positively associated with all six anthropometric measures, whereas lung cancer among ever smokers was significantly inversely associated with all measures except WHR. The derived cutoffs of each obesity measure varied across cancers (e.g., BMI cutoffs for breast and endometrium cancers were 30 kg/m(2) and 34 kg/m(2), respectively), and also depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10-year cancer incidence were higher among HT never users., Conclusion: Using a panel of different anthropometric measures, we derived optimal cut-offs categorizing populations into high- and low-risk groups, which differed by cancer type and HT use. Although the discrimination abilities of these risk categories were generally poor, the results of this study could serve as a starting point from which to determine adiposity cutoffs for inclusion in risk prediction models for specific cancer types.

Purpose: A body shape index (ABSI) has been proposed as a possible improvement over waist circumference (WC) as a marker of abdominal adiposity because it removes the correlation of WC with body mass index (BMI) and with height. We assessed the association of ABSI with four obesity-related cancers compared to that of other anthropometric measures of adiposity., Methods: We used data from the Women's Health Initiative, a large cohort of postmenopausal women, recruited between 1993 and 1998 and followed until September 2013, to assess the associations of ABSI and other anthropometric measures with risk of cancers of the breast, endometrium, colorectum, and kidney. The four comparison anthropometric measures were BMI, WC, waist circumference-to-height ratio (WHtR), and waist-hip ratio (WHR). Over a median of 12.7 years of follow-up, among 143,901 women, we identified 7,039 invasive breast cancers, 1,157 endometrial cancers, 1,908 colorectal cancers, and 376 kidney cancers. We used Cox proportional hazards models to estimate the association of quintiles of the five measures with risk of the four cancers., Results: Unlike the other anthropometric indices, ABSI was not associated with increased risk of breast or endometrial cancer. BMI and WC were comparable as predictors of breast and endometrial cancer, and these associations were unchanged after mutual adjustment. For colorectal and kidney cancers, ABSI was a significant predictor comparable to BMI; however, WC showed the strongest association with colorectal cancer, and WC, WHtR, and WHR all showed stronger associations with kidney cancer., Conclusion: In contrast to other anthropometric measures, ABSI showed no association with risk of breast or endometrial cancer and was more weakly associated with risk of colorectal and kidney cancers compared to more established measures of central adiposity.

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se., (©2014 American Association for Cancer Research.)

Purpose: Some studies suggest that anthropometric measures of abdominal obesity may be superior to body mass index (BMI) for the prediction of cardiometabolic risk factors; however, most studies have been cross-sectional. Our aim was to prospectively examine the association of change in BMI, waist-to-hip ratio (WHR), waist circumference (WC), and waist circumference-to-height ratio (WCHtR) with change in markers of cardiometabolic risk in a population of postmenopausal women., Methods: We used a subsample of participants in the Women's Health Initiative aged 50 to 79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (n = 2672). The blood samples were used to measure blood glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine associations at baseline and longitudinal associations between change in anthropometric measures and change in cardiometabolic risk factors, adjusting for covariates., Results: In longitudinal analyses, change in BMI, WC, and WCHtR robustly predicted change in cardiometabolic risk, whereas change in WHR did not. The strongest associations were seen for change in triglycerides, glucose, and HDL-C (inverse association)., Conclusion: Increase in BMI, WC, and WCHtR strongly predicted increases in serum triglycerides and glucose, and reduced HDL-C. WC and WCHtR were superior to BMI in predicting serum glucose, HDL-C, and triglycerides. WCHtR was superior to WC only in predicting serum glucose. BMI, WC, and WCHtR were all superior to WHR.

Purpose: To examine the association of adult height with risk of cancer at different anatomic sites in a cohort of men and women., Methods: The association of self-reported height with subsequent cancer risk was assessed in 288,683 men and 192,514 women enrolled in the National Institutes of Health-AARP Diet and Health Study. After a median follow-up of 10.5 years, incident cancer was diagnosed in 51,139 men and 23,407 women. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the association of height with cancer risk., Results: After adjustment for covariates, height was positively associated with increased risk of all cancers combined in both men [HR10 cm increase = 1.05 (95 % CI 1.04-1.06)] and women [HR10 cm increase = 1.08 (95 % CI 1.06-1.10)]. Several sites common to men and women showed significant positive associations with height: colon, rectum, kidney, melanoma, and non-Hodgkin's lymphoma. For other shared sites, the association differed by sex. For still other sites, there was no clear association with height. Positive associations were also observed with cancers of the breast, endometrium, and prostate., Conclusions: Different patterns were observed in the height-cancer association by sex. Studies investigating the biological mechanisms underlying the association of height with cancer risk should focus on those sites that show a reproducible association with attained height.

Background and Aims: Obesity has been associated with increased levels of hemostatic factors. However, few studies have compared change in different anthropometric measures of adiposity in relation to change in levels of hemostatic factors. Our aim was to examine prospectively the association of change in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and waist circumference-height ratio (WHtR) with change in markers of hemostasis in a population of postmenopausal women., Methods and Results: A subsample of women in the Women's Health Initiative (WHI) cohort had fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up. Of these, we studied the 2593 women who were not in the intervention arm of any WHI clinical trial. Their blood samples were used to measure plasma fibrinogen, factor VII antigen activity, and factor VII concentration at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine the longitudinal association between change in anthropometric factors and change in hemostatic factors, adjusting for a wide range of potential confounding factors. In longitudinal analyses using repeated measures, change in BMI, WC, and WHtR were all positively associated with change in all 3 hemostatic factors. Change in anthropometric variables was most strongly associated with change in fibrinogen., Conclusions: Our results suggest that an increase in adiposity over time is robustly associated with increased levels of hemostatic factors. Registration number of clinical trial: NCT00000611., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Testosterone supplementation is being prescribed increasingly to treat symptoms of hormone deficiency in pre- and postmenopausal women; however, studies of the association of testosterone therapy, alone or in combination with estrogen, with risk of breast cancer are limited. The current study assessed the association of combination conjugated esterified estrogen and methyltestosterone (CEE+MT) use and breast cancer risk in postmenopausal women in the Women's Health Initiative (WHI)., Study Design: At Year 3 of follow-up, women in the WHI observational study (N=71,964) provided information on CEE+MT use in the past two years, duration of use, and the brand name of the product. In addition, in each of years 4-8, women were asked whether they had used CEE+MT in the previous year. After 10 years of follow-up, 2832 incident breast cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association of CEE+MT use (irrespective of use of other hormones) and of exclusive CEE+MT use in relation to breast cancer risk., Results: Neither CEE+MT use nor exclusive use of CEE+MT was associated with risk: multivariable-adjusted HR 1.06, 95% CI 0.82-1.36 and HR 1.22, 95% CI 0.78-1.92, respectively. Among women with a natural menopause, the HR for exclusive use was 1.32 (95% CI 0.68-2.55). There was no indication of an association when repeated measures of CEE+MT use were included in a time-dependent covariates analysis., Conclusion: The present study, the largest prospective study to date, did not show a significant association of CEE+MT supplementation and risk of breast cancer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile = 1.80; 95% confidence interval, CI, 1.16-2.79; Ptrend = 0.003) as were levels of estradiol (OR for highest vs. lowest tertile = 1.89; 95% CI, 1.26-2.83; Ptrend = 0.02) and CRP (OR for highest vs. lowest quartile = 2.46; 95% CI, 1.59-3.80; Ptrend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile = 0.47; 95% CI, 0.31-0.71; Ptrend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development., (©2014 American Association for Cancer Research.)

Objective: Four body mass index (BMI) metrics--BMI, BMI z-score, BMI percentile and BMI%--are commonly used as proxy measures for children's adiposity. We sought to determine a BMI metric that is most strongly associated with measured percentage of body fat (%BF) in the US pediatric population stratified by sex, age and race/ethnicity, and to determine cutoffs that maximize the association for each BMI metric. SUBJECTS, DESIGN AND METHODS: %BF was measured by dual-energy X-ray absorptiometry among N=6120 US boys and girls aged 8.0-17.9 years old from the National Health and Nutrition Examination Survey 1999-2004. We fit piecewise linear regression models with cutoffs to %BF data using each BMI metric as the predictor stratified by sex, race/ethnicity and age. The slopes were modeled differently before and after the cutoffs which were determined on the basis of grid searches., Results: BMI z-score was in general most strongly associated with %BF for both boys and girls. The associations of the four BMI metrics were lowest for boys aged 12-13.9 years and girls aged 16-17.9 years, and strongest for Mexican-American boys and for non-Hispanic Black girls. Overall, the associations were stronger for girls than for boys. In boys, BMI had the lowest association with %BF (R(2)=0.39) for all ages combined. The fold changes in slopes before and after cutoffs were greatest in general for BMI percentiles regardless of age, sex and race/ethnicity. BMI z-score cutoffs were 0.4 for both boys and girls for all ages combined. Except for BMI, the slopes after the cutoffs were in general greater than those before., Conclusions: All BMI metrics were strongly associated with %BF when stratified by age and race/ethnicity except that BMI was the least associated with %BF in boys for all ages combined. Overall, BMI z-score was superior for evaluation of %BF, and its cutoff of 0.4 can also serve as a threshold for careful monitoring of weight status.

The incidence of cancer of the urinary bladder is three- to five-fold lower in women than in men. This difference may be partially explained by lower exposure to cigarette smoking and occupational chemicals. In addition, female endogenous hormones may also play a protective role in the etiology of this disease. However, limited information is available from cohort studies that have examined reproductive factors and hormone use in relation to the risk of bladder cancer. We assessed the association of menstrual and reproductive factors and exogenous hormone use with the risk of incident transitional cell cancer of the urinary bladder in a cohort of 145,548 postmenopausal women (ages 50-79 years at baseline) enrolled in the Women's Health Initiative. Over 12.7 years of follow-up, 480 cases of transitional cell bladder cancer were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the exposures of interest. Relative to nulliparous women, parous women had a reduced risk of transitional cell cancer: multivariable-adjusted HR 0.77, 95% CI 0.59-1.01; however, there was no clear trend with increasing number of births. Risk was significantly increased in women with a history of at least two miscarriages (HR 1.52, 95% CI 1.15-2.00). Neither other reproductive variables we studied nor the use of exogenous hormones, including type of hormone therapy, were associated with altered risk of bladder cancer. In conclusion, in this large prospective study of postmenopausal women, we found limited evidence for associations of reproductive factors or exogenous hormone use with the risk of bladder cancer.

Background: Body mass index (BMI; weight (Wt)/height (Ht) (in kg m(-2)) and waist circumference (WC) are widely used as proxy anthropometric measures for total adiposity. Little is known about what scaling power of 'x' in both Wt(kg)/Ht(m)(x) and WC(m)/Ht(m)(x) is maximally associated with measured total body fat mass (TBFM). Establishing values for x would provide the information needed to create optimum anthropometric surrogate measures of adiposity., Objective: To estimate the value of 'x' that renders Wt/Ht(x) and WC/Ht(x) maximally associated with DXA-measured TBFM., Subjects: Participants of the NHANES 1999-2004 surveys, stratified by sex (men, women), race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Mexican-Americans), and age(18-29, 30-49, 50-84 years)., Methods: We apply a grid search by increasing x from 0.0-3.0 by increments of 0.1 to the simple regression models, TBFM=b0+b1*(Wt/Ht(x)) and TBFM=b0+b1*(WC/Ht(x)) to obtain an estimate of x that results in the greatest R(2), taking into account complex survey design features and multiply imputed data., Results: R(2)'s for BMI are 0.86 for men (N=6544) and 0.92 for women (N=6362). The optimal powers x for weight are 1.0 (R(2)=0.90) for men and 0.8 (R(2)=0.96) for women. The optimal power x for WC is 0, that is, no scaling of WC to height, for men (R(2)=0.90) or women (R(2)=0.82). The optimal powers for weight across nine combinations of race/ethnicity and age groups for each sex vary slightly (x=0.8-1.3) whereas the optimal scaling powers for WC are all 0 for both sexes except for non-Hispanic black men aged 18-29y (x=0.1). Although the weight-for-height indices with optimal powers are not independent of height, they yield more accurate TBFM estimates than BMI., Conclusion: In reference to TBFM, Wt/Ht and Wt/Ht(0.8) are the optimal weight-for-height indices for men and women, respectively, whereas WC alone, without Ht adjustment, is the optimal WC-for-height index for both sexes. Thus, BMI, an index independent of height, may be less useful when predicting TBFM.

Background: Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors., Methods: We examined the association between height measured at enrollment in 144,701 women participating in the Women's Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers., Results: Height was significantly positively associated with risk of all cancers (HR = 1.13; 95% CI, 1.11-1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification., Conclusions: This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites., Impact: Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association., (©2013 AACR)

Studies of the relationship between anthropometric indices of obesity and colorectal cancer risk in women have shown only weak and inconsistent associations. Given the limitations of such indices, we used dual-energy X-ray absorptiometry (DXA)-derived measures of body fat obtained in the Women's Health Initiative to examine the association between body fat and risk of incident colorectal cancer. We compared these risk estimates with those obtained using conventional anthropometric measurements (body mass index and waist circumference). After exclusions, the study population consisted of 11,124 postmenopausal women with DXA measurements at baseline and no history of colorectal cancer. After a median follow-up period of 12.9 years, 169 incident colorectal cancer cases were ascertained. Cox's proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for the exposures of interest. Neither DXA-derived body fat measures nor anthropometric measures showed significant associations with risk. In view of the limited number of cases, we cannot rule out the existence of weak associations of these measures with risk of colorectal cancer.

Background: Aside from exposure to ionizing radiation and benzene, little is known about lifestyle risk factors for chronic myeloid leukemia (CML) in the general population., Methods: We examined the relation between lifestyle and dietary risk factors for CML in 493,188 participants (294,271 males and 198,917 females) aged 50 to 71 years who completed a baseline questionnaire in the National Institutes of Health-AARP Diet and Health Study in 1995 to 1996. Over a median of 10.5 years of follow-up, 178 incident cases of CML (139 males and 39 females) were ascertained from state registries. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for exposures of interest, adjusting for potential confounding variables., Results: In multivariable analysis of all participants combined, female sex, years of education, and vigorous physical activity (HR for ≥3 times/week vs. <1 time/week 0.70; 95% CI, 0.49-0.99) were inversely associated with risk of CML, whereas smoking intensity (HR for smokers of ≥20 cigarettes per day vs. never smokers: 1.53; 95% CI, 1.03-2.27) and body mass (HR for BMI ≥ 30 vs. <25 kg/m(2) 1.46; 95% CI, 0.95-2.23) were associated with increased risk. A range of dietary factors was not associated with disease., Conclusions: This study adds to the sparse information about lifestyle factors, which affect the risk of CML in the general population., Impact: If these findings are confirmed, it would suggest that CML may be amenable to preventive strategies.

Although the influence of body mass index on cancer risk has been intensively investigated, few epidemiologic studies have examined the association of adult height with risk of cancer. We assessed the association of height with risk of all cancer and of 19 site-specific cancers in the Canadian National Breast Screening Study, a prospective cohort of nearly 90,000 women. Weight and height were measured at enrollment, and information on reproductive and medical history as well as lifestyle exposures was obtained by means of questionnaire. After exclusions, 5,679 incident invasive cancers were identified among 88,256 women. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) per 10 cm increase in height. All tests of statistical significance were two sided. All cancers combined and ten specific sites (colorectum, colon, premenopausal breast, postmenopausal breast, endometrium, ovary, kidney, thyroid, melanoma and leukemia) showed statistically significant positive associations with height. The HR for all cancers combined was 1.13 (95% CI: 1.08-1.18), and the magnitude of the associations for specific sites ranged from HR 1.11 (95% CI: 1.03-1.20) for postmenopausal breast cancer to HR 1.51 (95% CI: 1.27-1.80) for melanoma. Our study provides strong support for a positive association of adult height with risk of certain cancers. The underlying biological mechanisms are not clear but may differ by anatomic site., (Copyright © 2012 UICC.)

Associations between anthropometric indices of obesity and breast cancer risk may fail to capture the true relationship between excess body fat and risk. We used dual-energy-X-ray-absorptiometry- (DXA-) derived measures of body fat obtained in the Women's Health Initiative to examine the association between body fat and breast cancer risk; we compared these risk estimates with those for conventional anthropometric measurements. The study included 10,960 postmenopausal women aged 50-79 years at recruitment, with baseline DXA measurements and no history of breast cancer. During followup (median: 12.9 years), 503 incident breast cancer cases were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. All baseline DXA-derived body fat measures showed strong positive associations with breast cancer risk. The multivariable-adjusted HR for the uppermost quintile level (versus lowest) ranged from 1.53 (95% CI 1.14-2.07) for fat mass of the right leg to 2.05 (1.50-2.79) for fat mass of the trunk. Anthropometric indices (categorized by quintiles) of obesity (BMI (1.97, 1.45-2.68), waist circumference (1.97, 1.46-2.65), and waist : hip ratio (1.91, 1.41-2.58)) were all strongly, positively associated with risk and did not differ from DXA-derived measures in prediction of risk.

Many studies have examined the associations of body mass index (weight (kg)/height (m)(2)) with risk of various cancers. However, optimal scaling of weight for height may depend on the population studied. The authors used data from a large cohort study of women (Canadian National Breast Cancer Screening Study, 1980-2000; n = 89,835) to examine how the scaling of weight for height (W/H(x)) influenced the association with risk of 19 different cancers. Cox proportional hazards models were used to estimate the hazard ratio for each cancer site with W/H(x), with x increasing from 0 to 3.0 by increments of 0.1. The correlation between weight and W/H(x) decreased monotonically with increasing x, whereas W/H(x) was minimally correlated with height when x = 1.4. W/H(x) showed significant positive associations with postmenopausal breast cancer, endometrial cancer, kidney cancer, and lung cancer in never smokers. W/H(x) was inversely associated with lung cancer in ever smokers. The value of x for which W/H(x) produced the largest statistically significant hazard ratio ranged from 0.8 (endometrial cancer) to 1.7 (postmenopausal breast cancer). For lung cancer in ever smokers, the inverse association was statistically significant for all values of x. These findings suggest that the scaling of weight for height may vary depending on the cancer site and that optimal scaling may be considerably different from W/H(2) or, alternatively, that a range of scaling should be considered when examining the association of body weight with risk of disease.

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we used interview data from a population-based sample of 1463 breast cancer cases and 1500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was used to account for biologically plausible nutrient pathways (1-carbon metabolism, oxidative stress, glycemic control, and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the 1-carbon metabolism, oxidative stress, and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer.

The metabolic syndrome is associated with increased risk of diabetes and coronary heart disease. Although higher BMI and other related factors have been frequently associated with colorectal cancer, whether the metabolic syndrome is associated with the risk of colorectal cancer is unclear. We therefore assessed the association of the metabolic syndrome with the risk of colorectal cancer in a subsample of participants of the Women's Health Initiative who had repeated measurements of the components of the syndrome at baseline and during follow-up. Women with diabetes at baseline enrollment were excluded. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) at baseline and in time-dependent analyses. Among 4862 eligible women, 81 incident cases of colorectal cancer were identified over a median follow-up of 12 years. Presence of the metabolic syndrome at baseline was associated with increased risk of colorectal cancer (HR 2.15, 95% CI 1.30-3.53) and colon cancer (HR 2.28, 95% CI 1.31-3.98). These associations were largely explained by positive associations of serum glucose and systolic blood pressure with both outcomes. Time-dependent covariate analyses supported the baseline findings. Our results suggest that the positive association of the metabolic syndrome with risk of colorectal cancer is largely accounted for by serum glucose levels and systolic blood pressure. The biological mechanism underlying these associations remains to be clarified.