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Introduction: The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy.Methods: We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (PACT).Results: The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (PACT= 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene PACT= 0.002; overall PACT= 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women.Conclusions: We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT. © 2011 Lee et al.; licensee BioMed Central Ltd.

Background: We investigated the association between hypertension, antihypertensive (AH) medication use, and breast cancer in a large prospective study, the California Teachers Study (CTS). Methods: Information on history of hypertension and lifetime regular use of AH medications was collected from 114,549 women in 1995-1996. Among them, 4,151 invasive breast cancers were diagnosed between 1995 and 2006. Additional information on AH use was collected from 73,742 women in 2000-2001, and 1,714 of these women were subsequently diagnosed with breast cancer. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for breast cancer. Results: Use of AH medication for ≥5 years, when compared with no use, was associated with a modest increased risk of invasive breast cancer (RR = 1.18, 95%CI 1.02-1.36). This increased risk appeared to be confined to estrogen receptor (ER)-positive tumors (RR = 1.21, 95%CI 1.03-1.43) and pre-/peri-menopausal women (RR = 1.58, 95%CI 1.11-2.25). Conclusions: Increased risk of invasive breast cancer was observed for long-term (≥5 years) AH use, and this appeared to be confined to ER + breast cancer and younger women. © 2010 The Author(s).

OBJECTIVE:To describe factors associated with vitamin supplement use in a large cohort of adult women. METHODS:California teachers and administrators (n = 133,479) completed a questionnaire on lifestyle factors and medical history. Specific supplement users regularly used at least one specific vitamin supplement in the past year; multivitamin users regularly used a multivitamin; and multivitamin and specific supplement users took a multivitamin and one or more specific supplements. Associations between supplement use and other variables were quantified using means, cross-tabulations, and age-adjusted prevalence odds ratios. RESULTS:Multivitamin and specific supplement users tended to be older and Caucasian. Compared to non-users, they were also leaner (odds ratio [OR] for BMI > or = 30 kg/m2 = 0.6 for specific supplement users with or without multivitamins, and OR = 0.7 for multivitamin only users), and were less likely to be current smokers (OR for current smoking = 0.8 for multivitamin plus specific supplement users, OR = 0.9 for specific supplement only users, and OR = 0.7 for multivitamin only users). Specific supplement users (with or without multivitamins) were more likely to use cancer screening tests, eat fruits and vegetables, and exercise than were multivitamin only users or non-users. CONCLUSIONS:A variety of demographic, dietary, and health-related factors were associated with different categories of supplement use.

Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.

Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.

With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined. [ABSTRACT FROM AUTHOR]

Background: Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites.Purpose: Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women.Methods: A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%).Results: A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate.Conclusions: Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life.Implications: Because heterogeneity in breast cancer risk in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer. [ABSTRACT FROM AUTHOR]

Objectives. We estimated trends in breast cancer incidence rates for specific Asian populations in California to determine if disparities exist by immigrant status and age. Methods. To calculate rates by ethnicity and immigrant status, we obtained data for 1998 through 2004 cancer diagnoses from the California Cancer Registry and imputed immigrant status from Social Security Numbers for the 26% of cases with missing birthplace information. Population estimates were obtained from the 1990 and 2000 US Censuses. Results. Breast cancer rates were higher among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI = 1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born Chinese and Filipina women who were younger than 55 years had higher rates than did White women of the same age. Rates increased over time in most groups, as high as 4% per year among foreign-born Korean and US-born Filipina women. From 2000DS2004, the rate among US-born Filipina women exceeded that of White women. Conclusions. These findings challenge the notion that breast cancer rates are uniformly low across Asians and therefore suggest a need for increased awareness, targeted cancer control, and research to better understand underlying factors. [ABSTRACT FROM AUTHOR]

Background: Cadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty., Objectives: To determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development., Methods: A cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth., Results: The baseline geometric mean creatinine-adjusted Cd concentration was 0.22 μg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 μg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 μg/L (hazard ratio = 0.42; 95% confidence interval, 0.23-0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline., Conclusions: These findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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

Purpose: Obesity is a public health epidemic and a major risk factor for endometrial cancer. Here, we identify key aspects of body size which jointly, over the life-course (since adolescence), are associated with endometrial cancer risk., Methods: Among 88,142 participants in the California Teachers Study, 887 were diagnosed with invasive type 1 endometrial cancer between 1997-1998 and 2012. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI) for endometrial cancer associated with life-course body size phenotypes, which incorporated validated measures., Results: Among women currently using hormone therapy, endometrial cancer risk was only associated with height (HR 1.78, 95% CI 1.32-2.40 for ≥67 vs. <67 inches). Among women not using hormone therapy, tall women who were overweight/obese in adolescence (HR 4.33, 95% CI 2.51-7.46) or who became overweight/obese as adults (HR 4.74, 95% CI 2.70-8.32) were at greatest risk., Conclusions: Considering absolute body mass, changes in adiposity over time, and body fat distribution together, instead of each measure alone, we identified lifetime obesity phenotypes associated with endometrial cancer risk. These results more clearly define specific risk groups, and may explain inconsistent findings across studies, improve risk prediction models, and aid in developing targeted interventions for endometrial cancer., Competing Interests: The authors declare they have no conflict of interest.

Background: Data are limited on effective methods for recruiting persons, especially from ethnically diverse populations, into population-based studies. The goal of this study was to evaluate the variation among and representativeness of controls identified using multiple methods for a population-based case-control study of breast cancer among Asian Americans, Native Hawaiians and Pacific Islanders (AANHPIs) in the San Francisco Bay Area., Methods: We used a unique combination of targeted recruitment strategies, including address-based sampling, community-based methods, and internet-based and media-based approaches for recruiting controls, frequency matched on age and ethnicity to a population-based sample of cases. To characterise the participating controls, we compared the distribution of sociodemographic characteristics and cancer risk factors between recruitment sources using χ(2) tests. To ensure that the controls we recruited were representative of the underlying at-risk population, we compared characteristics of the controls, by ethnicity and in aggregate, to data from the California Health Interview Survey (CHIS), and adjusted the relative mix of recruitment strategies throughout the study as needed to achieve representativeness., Results: As expected, controls (n=483) recruited by any single method were not representative. However, when aggregated across methods, controls were largely representative of the underlying source population, as characterised by CHIS, with regard to the characteristics under study, including nativity, education, marital status and body mass index., Conclusions: A multimode approach using targeted recruitment strategies is an effective and feasible alternative to using a single recruitment method in identifying a representative, diverse control sample for population-based studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Endometrial cancer is the most common gynecological malignancy in the developed world. Although there is evidence of genetic predisposition to the disease, most of the genetic risk remains unexplained. We present the meta-analysis results of four genome-wide association studies (4907 cases and 11 945 controls total) in women of European ancestry. We describe one new locus reaching genome-wide significance (P < 5 × 10 - 8 ) at 6p22.3 (rs1740828; P = 2.29 × 10 - 8 , OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts., Methods: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model., Results: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status., Conclusions: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality., Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information., Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04-1.10], BMI (per 5 kg/m2) = 1.06 [1.02-1.10], waist circumference (per 5 cm) = 1.03 [1.01-1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02-1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality., Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites., Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers., Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures., Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation., (Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Little epidemiologic research has focused on the role of immune function in papillary thyroid cancer risk despite scattered observations suggesting it may be important (e.g., hygiene hypothesis). Here we investigate papillary thyroid cancer risk associated with self-reported living environments across the lifespan reflecting immunologically relevant exposures to microbial-rich environments., Methods: Among 61,803 eligible participants in the California Teachers Study cohort, 100 were diagnosed with invasive papillary thyroid cancer between 2005 and 2012. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Results: Living in a rural area during early childhood was associated with significantly reduced risk of developing papillary thyroid cancer as an adult (HR=0.51, 95% CI: 0.28-0.94). Specifically, reduced risks were observed for living within a half mile of hoofed animals (HR=0.47, 95% CI: 0.26-0.84), as was having an indoor dog or cat (HR=0.51, 95% CI: 0.32-0.80). Neither sharing a bedroom or living in a rented home as a child nor attending daycare or kindergarten was associated with reduced risk., Conclusions: Early childhood exposures to hoofed animals or indoor furry pets were associated with reduced risk of subsequently developing papillary thyroid cancer., Impact: Our findings point to immunologically relevant, early-life exposures to microbial-rich environments as potentially important in reducing thyroid cancer risk, consistent with the hygiene hypothesis and suggesting that certain, possibly animal-derived, microbial exposures may be important to immune calibration or priming., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Few studies have focused on prognostic factors among adolescents and young adults (AYAs) 15 to 39 years of age when diagnosed with differentiated thyroid cancer (DTC). Our study expands upon prior work by including an evaluation of survival among AYA men and by neighborhood socioeconomic status, health insurance, and clinical factors to identify subgroups of young DTC patients at higher risk of mortality., Methods: Data for 16,827 AYA DTC patients diagnosed between 1988 and 2010 were obtained from the California Cancer Registry. Survival, through 2010, by sociodemographic and clinical factors was analyzed using Cox proportional hazards regression., Results: Of the 2.1% of AYAs who died, 16.7% died from thyroid cancer and 21.4% died from a subsequent cancer. In multivariate analyses, older AYAs 35 to 39 year of age (versus 15- to 29-year-olds), men (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.62-4.72), and AYAs of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer specific survival. In addition, residing in low socioeconomic status neighborhoods (HR 3.11 [CI 1.28-7.56]) and nonmetropolitan areas (HR 5.53 [CI 2.07-14.78]) was associated with worse thyroid cancer-specific survival among AYA men, but not AYA women., Conclusions: Despite the generally good prognosis among AYAs with DTC, we identified subgroups of AYA patients at risk for poor outcomes. Further study of the factors underlying these associations, including possible barriers to receiving high-quality treatment and follow-up care, as well as lifestyle factors, are critical to reducing these disparities.

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

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥ 35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥ 45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥ 10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes., (© 2014 UICC.)

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

The Asian American, Native Hawaiian, and Pacific Islander population is large, growing, and extremely heterogeneous. Not only do they bear unique burdens of incidence and outcomes for certain cancer types, they exhibit substantial variability in cancer incidence and survival patterns across the ethnic groups. By acknowledging and leveraging this heterogeneity through investing in cancer research within these populations, we have a unique opportunity to accelerate the availability of useful and impactful cancer knowledge. See all the articles in this CEBP Focus section, "Cancer in Asian and Pacific Islander Populations.", (©2014 American Association for Cancer Research.)

Background: There is convincing evidence that circadian disruption mediated by exposure to light at night promotes mammary carcinogenesis in rodents. The role that light at night plays in human breast cancer etiology remains unknown. We evaluated the relationship between estimates of indoor and outdoor light at night and the risk of breast cancer among members of the California Teachers Study., Methods: Indoor light-at-night estimates were based on questionnaire data regarding sleep habits and use of nighttime lighting while sleeping. Estimates of outdoor light at night were derived from imagery data obtained from the US Defense Meteorological Satellite Program assigned to geocoded addresses of study participants. Analyses were conducted among 106,731 California Teachers Study members who lived in California, had no prior history of breast cancer, and provided information on lighting while sleeping. Five thousand ninety-five cases of invasive breast cancer diagnosed 1995-2010 were identified via linkage to the California Cancer Registry. We used age-stratified Cox proportional hazard models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for breast cancer risk factors and neighborhood urbanization and socioeconomic class., Results: An increased risk was found for women living in areas with the highest quintile of outdoor light-at-night exposure estimates (HR = 1.12 [95% CI = 1.00-1.26]; test for trend, P = 0.06). Although more pronounced among premenopausal women (HR = 1.34 [95% CI = 1.07-1.69]; test for trend, P = 0.04), the associations did not differ statistically by menopausal status (test for interaction, P = 0.34)., Conclusions: Women living in areas with high levels of ambient light at night may be at an increased risk of breast cancer. Future studies that integrate quantitative measurements of indoor and outdoor light at night are warranted.

Introduction: Diabetes mellitus (DM) is an important risk factor for endocrine cancers; however, the association with thyroid cancer is not clear. We performed a systematic review and meta-analysis to clarify the association between thyroid cancer and DM., Methods: We searched MEDLINE, PUBMED and EMBASE databases through July 2012, using search terms related to diabetes mellitus, cancer, and thyroid cancer. We conducted a meta-analysis of the risk of incidence of thyroid cancer from pre-existing diabetes. Of 2,123 titles initially identified, sixteen articles met our inclusion criteria. An additional article was identified from a bibliography. Totally, 14 cohort and 3 case-control studies were selected for the meta-analysis. The risks were estimated using random-effects model and sensitivity test for the studies which reported risk estimates and used different definition of DM., Results: Compared with individuals without DM, the patients with DM were at 1.34-fold higher risk for thyroid cancer (95% CI 1.11-1.63). However, there was heterogeneity in the results (p<0.0001). Sensitivity tests and studies judged to be high quality did not show heterogeneity and DM was associated with higher risk for thyroid cancer in these sub-analyses (both of RRs = 1.18, 95% CIs 1.08-1.28). DM was associated with a 1.38-fold increased risk of thyroid cancer in women (95% CI 1.13-1.67) after sensitivity test. Risk of thyroid cancer in men did not remain significant (RR 1.11, 95% CI 0.80-1.53)., Conclusions: Compared with their non-diabetic counterparts, women with pre-existing DM have an increased risk of thyroid cancer.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Thyroid cancer incidence is increasing worldwide. Incorporating 22 years of incidence data through 2009, we extend examination of these trends among a wide array of subgroups defined by patient (age, sex, race/ethnicity, and nativity), tumor (tumor size and stage), and neighborhood (socioeconomic status and residence in ethnic enclaves) characteristics, to identify possible reasons for this increase., Methods: Thyroid cancer incidence data on 10,940 men and 35,147 women were obtained from the California Cancer Registry for 1988-2009. Population data were obtained from the 1990 and 2000 U.S. Census. Incidence rates and 95% confidence intervals (CI) were calculated and incidence trends were evaluated using Joinpoint regression to evaluate the timing and magnitude of change [annual percentage change (APC) and rate ratios]., Results: The incidence of papillary thyroid cancer continues to increase in both men (APC, 5.4; 95% CI, 4.5-6.3 for 1998-2009) and women (APC, 3.8; 95% CI, 3.4-4.2 for 1998-2001 and APC, 6.3; 95% CI, 5.7-6.9 for 2001-2009). Increasing incidence was observed in all subgroups examined., Conclusions: Although some variation in the magnitude or temporality of the increase in thyroid cancer incidence exists across subgroups, the patterns (i) suggest that changes in diagnostic technology alone do not account for the observed trends and (ii) point to the importance of modifiable behavioral, lifestyle, or environmental factors in understanding this epidemic., Impact: Given the dramatic and continued increase in thyroid cancer incidence rates, studies addressing the causes of these trends are critical. Cancer Epidemiol Biomarkers Prev; 23(6); 1067-79. ©2014 AACR., (©2014 American Association for Cancer Research.)

Objectives: To assess the independent effect of waist circumference on mortality across the entire body mass index (BMI) range and to estimate the loss in life expectancy related to a higher waist circumference., Patients and Methods: We pooled data from 11 prospective cohort studies with 650,386 white adults aged 20 to 83 years and enrolled from January 1, 1986, through December 31, 2000. We used proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for the association of waist circumference with mortality., Results: During a median follow-up of 9 years (maximum, 21 years), 78,268 participants died. After accounting for age, study, BMI, smoking status, alcohol consumption, and physical activity, a strong positive linear association of waist circumference with all-cause mortality was observed for men (HR, 1.52 for waist circumferences of ≥110 vs <90 cm; 95% CI, 1.45-1.59; HR, 1.07 per 5-cm increment in waist circumference; 95% CI, 1.06-1.08) and women (HR, 1.80 for waist circumferences of ≥95 vs <70 cm; 95% CI, 1.70-1.89; HR, 1.09 per 5-cm increment in waist circumference; 95% CI, 1.08-1.09). The estimated decrease in life expectancy for highest vs lowest waist circumference was approximately 3 years for men and approximately 5 years for women. The HR per 5-cm increment in waist circumference was similar for both sexes at all BMI levels from 20 to 50 kg/m(2), but it was higher at younger ages, higher for longer follow-up, and lower among male current smokers. The associations were stronger for heart and respiratory disease mortality than for cancer., Conclusions: In white adults, higher waist circumference was positively associated with higher mortality at all levels of BMI from 20 to 50 kg/m(2). Waist circumference should be assessed in combination with BMI, even for those in the normal BMI range, as part of risk assessment for obesity-related premature mortality., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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

Background: Evidence that diet is associated with breast cancer risk is inconsistent. Most studies have examined risks associated with specific foods and nutrients, rather than measures of overall diet., Objective: This study aimed to evaluate dietary patterns and their relation to breast cancer risk in a large cohort of women., Design: Data from 91,779 women in the California Teachers Study cohort were analyzed, including data from 4140 women with a diagnosis of invasive breast cancer made between 1995 and 2009. Five predominant dietary patterns were identified by using principal components factor analysis: a plant-based diet, high in fruit and vegetables; a high-protein, high-fat diet, high in meats, eggs, fried foods, and high-fat condiments; a high-carbohydrate diet, high in convenience foods, pasta, and bread products; an ethnic diet, high in legumes, soy-based foods, rice, and dark-green leafy vegetables; and a salad and wine diet, high in lettuce, fish, wine, low-fat salad dressing, and coffee and tea., Results: The plant-based pattern was associated with a reduction in breast cancer risk (RR: 0.85; 95% CI: 0.76, 0.95 for the highest compared with the lowest consumption quintile; P-trend = 0.003); risk reduction was greater for estrogen receptor-negative progesterone receptor-negative (ER-PR-) tumors (RR: 0.66; 95% CI: 0.48, 0.91; P-trend = 0.03). The salad and wine pattern was associated with an increased risk of estrogen receptor-positive progesterone receptor-positive tumors (RR: 1.29; 95% CI: 1.12, 1.49); this effect was only slightly attenuated after adjustment for alcohol consumption., Conclusion: The finding that greater consumption of a plant-based dietary pattern is associated with a reduced breast cancer risk, particularly for ER-PR- tumors, offers a potential avenue for prevention.

Female steroid hormones are hypothesized to play a protective role in pancreatic cancer risk. However, results from epidemiologic studies that examined hormone-related exposures have been inconsistent. The California Teachers Study is a cohort study of female public school professionals that was established in 1995-1996. Of the 118,164 eligible study participants, 323 women were diagnosed with incident invasive pancreatic cancer through December 31, 2009. Multivariable Cox proportional hazards regression methods were used to estimate hazard ratios and 95% confidence intervals for the association of pancreatic cancer risk with reproductive factors and exogenous hormone use. Current users of estrogen-only therapy at baseline (1995-1996) had a lower risk of pancreatic cancer than did participants who had never used hormone therapy (hazard ratio = 0.59, 95% confidence interval: 0.42, 0.84). Use of estrogen-plus-progestin therapy was not associated with the risk of pancreatic cancer. A longer duration of oral contraceptive use (≥10 years of use compared with never use) was associated with an increased risk of cancer (hazard ratio = 1.72, 95% confidence interval: 1.19, 2.49). Reproductive factors, including age at menarche, parity, breastfeeding, and age at menopause, were not associated with pancreatic cancer risk. Our results suggest that increased estrogen exposure through estrogen-only therapy may reduce pancreatic cancer risk in women.

Background: Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size., Methods: Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size., Results: Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95% CI, 0.63-0.92). This inverse association was observed among overweight/obese women (body mass index ≥25 kg m(-2); Ptrend=0.006), but not among thinner women (Ptrend=0.12). Baseline moderate activity was associated with lower risk among overweight/obese women., Conclusion: Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.

Purpose: Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors., Patients and Methods: Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors., Results: Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar., Conclusion: The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.

Background: Cadmium (Cd) is a toxic metal associated with increased morbidity and mortality. Urinary Cd (U-Cd) concentration is considered a biomarker of long-term exposure., Objectives: Our objectives were to evaluate the within-person correlation among repeat samples and to identify predictors of U-Cd concentrations., Methods: U-Cd concentrations (micrograms per liter) were measured in 24-hr urine samples collected from 296 women enrolled in the California Teachers Study in 2000 and a second 24-hr sample collected 3-9 months later from 141 of the participants. Lifestyle and sociodemographic characteristics were obtained via questionnaires. The Total Diet Study database was used to quantify dietary cadmium intake based on a food frequency questionnaire. We estimated environmental cadmium emissions near participants' residences using a geographic information system., Results: The geometric mean U-Cd concentration was 0.27 µg/L and the range was 0.1-3.6 µg/L. The intraclass correlation among repeat samples from an individual was 0.50. The use of a single 24-hr urine specimen to characterize Cd exposure in a case-control study would result in an observed odds ratio of 1.4 for a true odds ratio of 2.0. U-Cd concentration increased with creatinine, age, and lifetime pack-years of smoking among ever smokers or lifetime intensity-years of passive smoking among nonsmokers, whereas it decreased with greater alcohol consumption and number of previous pregnancies. These factors explained 42-44% of the variability in U-Cd concentrations., Conclusion: U-Cd levels varied with several individual characteristics, and a single measurement of U-Cd in a 24-hr sample did not accurately reflect medium- to long-term body burden.

Background: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes., Methods: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma., Results: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01)., Conclusion: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Background: Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer., Methods: Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided., Results: Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04)., Conclusions: We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.

Purpose: Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women., Methods: 116,939 women in the California Teachers Study, aged 22-79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort)., Results: Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR = 0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m(2), trend p = 0.03) than among overweight or obese women (trend p = 0.35; homogeneity-of-trends p = 0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m(2), trend p = 0.11; BMI≥25 kg/m(2), trend p = 0.16; homogeneity-of-trends p = 0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood)., Conclusions: Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today., Methods: Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI)., Results: Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users [RR, 1.60; 95% confidence interval (CI), 1.13-2.26 and RR, 2.11; 95% CI, 1.41-3.15 for <20 and ≥20 g/d of alcohol], with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3 to 4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for estrogen receptor positive (ER+) and ER+PR+ progesterone receptors positive (PR+) tumors; while power was limited, no increase in risk was observed for ER- tumors., Conclusions: Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a nonsignificant increased risk was observed among women who never used HT., Impact: Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced., (©2012 AACR.)

Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7-20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.

We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in the hormone metabolism in 286 endometrial cancer cases and 488 controls. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each haplotype using unconditional logistic regression, adjusting for age. The strongest interaction was observed between duration of estrogen therapy (ET) use and haplotype 1A in CYP11A1 (p(interaction) = 0.0027; p(interaction) = 0.010 after correcting for multiple testing within each gene). The OR for endometrial cancer per copy of haplotype 1A was 2.00 (95% CI: 1.05-3.96) for long-term ET users and 0.90 (95% CI: 0.69-1.18) for never users. The most significant interaction with estrogen-progestin therapy (EPT) was found for two haplotypes on CYP19A1 and EPT use (haplotype 4A, p(interaction) = 0.024 and haplotype 3B, p(interaction) = 0.043). However, neither this interaction, nor the ET or EPT interactions for any other genes, was statistically significant after correction for multiple testing. Variations in CYP11A1 may modify the effect of ET use on risk of postmenopausal endometrial cancer; however, larger studies are needed to explore these findings further., (Copyright © 2011 UICC.)

Objectives: We considered interactions between physical activity and body mass index (BMI) and neighborhood factors., Methods: We used recursive partitioning to identify predictors of low recreational physical activity (< 2.5 hours/week) and overweight and obesity (BMI ≥ 25.0 kg/m(2)) among 118,315 women in the California Teachers Study. Neighborhood characteristics were based on 2000 US Census data and Reference US business listings., Results: Low physical activity and being overweight or obese were associated with individual sociodemographic characteristics, including race/ethnicity and age. Among White women aged 36 to 75 years, living in neighborhoods with more household crowding was associated with a higher probability of low physical activity (54% vs 45% to 51%). In less crowded neighborhoods where more people worked outside the home, the existence of fewer neighborhood amenities was associated with a higher probability of low physical activity (51% vs 46%). Among non-African American middle-aged women, living in neighborhoods with a lower socioeconomic status was associated with a higher probability of being overweight or obese (46% to 59% vs 38% in high-socioeconomic status neighborhoods)., Conclusions: Associations between physical activity, overweight and obesity, and the built environment varied by sociodemographic characteristics in this educated population.

Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited., Objective: We investigated these associations in a pooled analysis of 18 cohort studies., Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model., Results: α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer., Conclusions: Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.