Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey... more
Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.
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Epidemiological studies have demonstrated a strong association between tobacco use and lung cancer; however, the genetic targets of these carcinogens and the role of other environmental agents in this process have yet to be defined. We... more
Epidemiological studies have demonstrated a strong association between tobacco use and lung cancer; however, the genetic targets of these carcinogens and the role of other environmental agents in this process have yet to be defined. We examined the contribution of alcohol use and cigarette smoking top53 gene mutations in patients with non-small cell lung cancer. Mutations of the p53 gene were detected by sequence analysis in 105 patients with non-small cell lung cancer. Patient characteristics significantly associated with p53 gene mutations were determined using logistic regression. Mutations in the p53 gene were present in 53% of the patients (56 of 105). p53 mutations were more common in patients who used alcohol than in patients who consumed less than one drink per day (72 versus 39%; P = 0.003), and were detected more often smokers than nonsmokers (58% versus 10%, P = 0.02). Mutations in the p53 gene were present more often (P = 0.01) in alcohol drinkers who smoked cigarettes [...
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Ovarian cancer risk factors differ by histotype; however, within subtype there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and... more
Ovarian cancer risk factors differ by histotype; however, within subtype there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n=864), very aggressive (death in 1-<3 years, n=1,390), moderately aggressive (death in 3-<5 years, n=639), and less aggressive (lived 5+ years, n=1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (p =0.01), family history of ovarian cancer (p =0.02), body mass index (BMI; p ≤0.04) and smoking (p <0.01) and ovarian cancer risk differed by aggressiveness. A first/single p...
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To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study. We pooled data on 2854 cases and 10 743 controls from nine studies... more
To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study. We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect. Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumu...
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The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk... more
The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, ...
Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2... more
Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic...
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Using pooled multivariable-adjusted rate ratios (RR), we explored relationships between prediagnostic body-mass-index (BMI), waist-to-hip-ratio (WHR), and weight-gain during adulthood, and ALS in 419,894 women and 148,166 men from 10... more
Using pooled multivariable-adjusted rate ratios (RR), we explored relationships between prediagnostic body-mass-index (BMI), waist-to-hip-ratio (WHR), and weight-gain during adulthood, and ALS in 419,894 women and 148,166 men from 10 community-based cohorts in USA, Europe, and Australia; 428 ALS deaths were documented in women and 204 in men. Higher mid-to-later adulthood BMI was associated with lower ALS mortality. For 5 kg/m increased BMI, the rate was 15% lower (95% confidence interval [CI]: 4-24%; p = 0.005). Although a clear linear trend was not evident for WHR at enrollment (p = 0.099) individuals in the highest cohort-specific quartile had 27% (95% CI: 0-47%; p = 0.053) lower ALS compared to those in the lowest. BMI in early adulthood did not predict ALS; fewer than 10% of participants had early adulthood BMI >25 kg/m, limiting power. Weight-gain during adulthood was strongly associated with lower ALS; for an additional 1kg gain in weight/year, the RR = 0.43 (95% CI: 0.28-...
Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with... more
Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these. We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association ...
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Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and... more
Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for...
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Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week... more
Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic mino...
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Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer... more
Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35-64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women. BMI at age 18 years was inve...
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Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between... more
Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. We investigated associations between TNF-α -308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1 Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years). Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. Carriers of the PPARγ variant allele had statistically significantly lower r...
After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal... more
After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal trends in serum PFAS levels among 1257 middle-aged and older California women (ages 40-94) during a four year period, beginning approximately 5-10 years after these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long-chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from a subset of participants in the California Teachers Study. Results from multivariable linear regression analyses indicated that serum concentrations of nearly all PFASs declined on average 10% to 20% per year. Serum levels of perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the exception of PFHxS, the downward trend in serum concentrations was evident for all PFASs across all ages, although declines were comparativel...
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We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors. We used pooled data from 3288 patients with BE, 2511 patients with EAC, and... more
We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors. We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett's and EAC consortium as well as the United Kingdom's BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations o...
Research Interests: Gastroenterology, Australia, Life Style, Molecular Epidemiology, Humans, and 15 moreEurope, Female, Male, Phenotype, Clinical Sciences, North America, Middle Aged, Odds ratio, Neurosciences, Logistic Models, Area Under Curve, Adenocarcinoma, Case Control Studies, Decision Support Techniques, and Paediatrics and reproductive medicine
We examined the degree of over- and under-reporting of cardiovascular diseases (CVDs) among female breast cancer survivors comparing self-reports to diagnostic codes from the Danish National Patient Register (NPR). The study comprised 357... more
We examined the degree of over- and under-reporting of cardiovascular diseases (CVDs) among female breast cancer survivors comparing self-reports to diagnostic codes from the Danish National Patient Register (NPR). The study comprised 357 Danish breast cancer patients from the WECARE study who completed a telephone interview concerning CVDs. Disease diagnoses for these women were obtained from the NPR. Agreement was calculated as the number of diagnoses that were both self-reported and in the NPR divided by (1) number of self-reported diagnoses (over-reporting) or (2) number of diagnoses in the NPR (under-reporting). In total, 68 women reported 96 specific cardiovascular outcomes of which 56 (58%) were found in the NPR. Ninety cardiovascular diagnoses were found in the NPR of which 56 (62%) were specifically reported at the interview. There was 80% agreement as to the occurrence of a cardiovascular diagnosis overall. Of 289 women reporting no CVD, 273 (94%) had no diagnoses in the N...
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Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report... more
Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10(-8). The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide ave...
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Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594... more
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10(-8) with ten variants at nine new loci. At P…
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Research Interests: Risk, Multivariate Analysis, California, Stroke, Humans, and 15 moreFemale, Exercise, School Teachers, Incidence, Clinical Sciences, Aged, Middle Aged, Adult, American Heart Association, Self report, Neurosciences, Proportional Hazards Models, Leisure Activities, Guideline Adherence, and Cardiovascular medicine and haematology
Personal predictive models for disease development play important roles in chronic disease prevention. The performance of these models is evaluated by applying them to the baseline covariates of participants in external cohort studies,... more
Personal predictive models for disease development play important roles in chronic disease prevention. The performance of these models is evaluated by applying them to the baseline covariates of participants in external cohort studies, with model predictions compared to subjects' subsequent disease incidence. However, the covariate distribution among participants in a validation cohort may differ from that of the population for which the model will be used. Since estimates of predictive model performance depend on the distribution of covariates among the subjects to which it is applied, such differences can cause misleading estimates of model performance in the target population. We propose a method for addressing this problem by weighting the cohort subjects to make their covariate distribution better match that of the target population. Simulations show that the method provides accurate estimates of model performance in the target population, while un-weighted estimates may no...
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Background: Few studies have focused on the relationship of exonic variation with breast cancer and subtypes defined by tumor markers: estrogen receptor (ER), progesterone receptor (PR), and HER2.Methods: We genotyped 1,764 breast cancer... more
Background: Few studies have focused on the relationship of exonic variation with breast cancer and subtypes defined by tumor markers: estrogen receptor (ER), progesterone receptor (PR), and HER2.Methods: We genotyped 1,764 breast cancer patients and 1,400 controls from the California Teachers Study cohort using the Infinium HumanExome Beadchip. Individual variant and gene-based analyses were conducted for overall breast cancer and by individual tumor marker subtype.Results: No exonic variants or gene-based analyses were statistically significantly associated with breast cancer overall or by ER-, PR-, or HER2-defined subtype.Conclusions: We did not detect any novel statistically significant exonic variants with overall breast cancer risk or by subtype.Impact: Exonic variants in the exome chip may not be associated with overall breast cancer or subtype susceptibility. Cancer Epidemiol Biomarkers Prev; 26(9); 1462-5. ©2017 AACR.
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Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family... more
Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history. The Women's Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tum...
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A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant... more
A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women ...
Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in... more
Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This paper describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June ...
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Genome-wide association studies have identified ~100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Due to different patterns of linkage disequilibrium,... more
Genome-wide association studies have identified ~100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Due to different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER and ROOT). Fifty-four of the 74 variants (73%) were found to have odds ratios that were directionally consistent with those previously reported, of which twelve were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13) we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions ...
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In response to health concerns and widespread human exposures, two widely used commercial formulations of polybrominated diphenyl ethers (PBDEs) were banned in the United States in 2005. Initial biomonitoring data have provided early... more
In response to health concerns and widespread human exposures, two widely used commercial formulations of polybrominated diphenyl ethers (PBDEs) were banned in the United States in 2005. Initial biomonitoring data have provided early indications of reduced human exposures since these bans took effect. Our objective was to evaluate temporal trends in PBDE serum levels among a population of older California women during a four-year period, beginning approximately five years after these formulations were banned. Automated solid phase extraction and gas chromatography/high resolution mass spectrometry were used to measure PBDE levels in blood collected during 2011-2015 among 1253 women (ages 40-94) participating in the California Teachers Study. Only congeners with detection frequencies (DF) ≥ 75% were included in the present analysis: BDE-47 (DF = 88%); BDE-100 (DF = 78%); and BDE-153 (DF = 80%). Results from age- and race/ethnicity-adjusted linear regression analyses indicated modest,...
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Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size... more
Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m(2), HR: 1.24; 95% CI, 1.13-1.35), young adult ...
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Large-scale environmental epidemiologic studies often rely on exposure estimates based on linkage to residential addresses. This approach, however, is limited by the lack of residential histories typically available for study... more
Large-scale environmental epidemiologic studies often rely on exposure estimates based on linkage to residential addresses. This approach, however, is limited by the lack of residential histories typically available for study participants. Our objective was to evaluate the feasibility of using address data from LexisNexis (a division of RELX, Inc., Dayton, Ohio), a commercially available credit reporting company, to construct residential histories for participants in the California Teachers Study (CTS), a prospective cohort study initiated in 1995-1996 to study breast cancer (n = 133,479). We evaluated the degree to which LexisNexis could provide retrospective addresses prior to study enrollment, as well as the concordance with existing prospective CTS addresses ascertained at the time of the completion of 4 self-administered questionnaires. For approximately 80% of CTS participants, LexisNexis provided at least 1 retrospective address, including nearly 25,000 addresses completely e...
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Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains unclear whether all of these are risk... more
Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains unclear whether all of these are risk factors for triple-negative breast cancer (TNBC). We evaluated the associations of these reproductive factors with TNBC, in 2658 patients with breast cancer (including 554 with TNBC) and 2448 controls aged 20-64 years, who participated in one of the three population-based case-control studies: the Women's Contraceptive and Reproductive Experiences Study, the Women's Breast Carcinoma in situ Study, or the Women's Learning the Influence of Family and Environment Study. We used multivariable polychotomous unconditional logistic regression methods to conduct case-control comparisons among breast cancer subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression status. TNBC risk decrease...
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Traditional methodologies for identifying and recruiting controls in epidemiologic case-control studies, such as random digit dialing or neighborhood walk, suffer from declining response rates. Here, we revisit the feasibility and... more
Traditional methodologies for identifying and recruiting controls in epidemiologic case-control studies, such as random digit dialing or neighborhood walk, suffer from declining response rates. Here, we revisit the feasibility and comparability of using alternative sources of controls, specifically friend and family controls. We recruited from a recently completed case-control study of non-Hodgkin lymphoma (NHL) among women in Los Angeles County where controls from the parent study were ascertained by neighborhood walk. We calculated participation rates and compared questionnaire responses between the friend/family controls and the original matched controls from the parent study. Of the 182 NHL case patients contacted, 111 (61%) agreed to participate in our feasibility study. 70 (63%) provided contact information for potential friend and/or family member controls. We were able to successfully contact and recruit a friend/family member for 92% of the case patients. This represented 4...
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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... more
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. 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). 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;...
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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. Among... more
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. 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. 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. Considering abso...
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Studies examining the relationship between body mass index (BMI) and risk of contralateral breast cancer (CBC) have reported mixed findings. We previously showed that obese postmenopausal women with estrogen receptor (ER)-negative breast... more
Studies examining the relationship between body mass index (BMI) and risk of contralateral breast cancer (CBC) have reported mixed findings. We previously showed that obese postmenopausal women with estrogen receptor (ER)-negative breast cancer have a fivefold higher risk of CBC compared with normal weight women. In the current analysis, we reexamined this relationship in the expanded Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study, focusing on the impact of menopausal status and ER status of the first breast cancer. The WECARE Study is a population-based case-control study of young women with CBC (cases, N = 1386) and with unilateral breast cancer (controls, N = 2045). Rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess the relationship between BMI and risk of CBC stratified by menopausal and ER status. Positive associations with obesity and weight gain were limited to women who became postmenopausal following their first primary ...
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Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707)... more
Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707) were diagnosed with stage I-IIIA breast cancer. Participants completed a 30-month post-diagnosis interview including questions on CAM use (natural products such as dietary and botanical supplements, alternative health practices, and alternative medical systems), weight, physical activity, and comorbidities. Outcomes were breast cancer-specific and total mortality, which were ascertained from the Surveillance Epidemiology and End Results registries in Western Washington, Los Angeles County, and New Mexico. Cox proportional hazards regression models were fit to data to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for mortality. Models were adjusted for potential confounding by sociodemographic, health, and cancer-related factors. Amo...
Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's... more
Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. We did a meta-analysis of all genome-wide association studies of…
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Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its... more
Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. We identified a significa...
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Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. A behavioral stress test was given to premenopausal (n = 13) and postmenopausal women (n =... more
Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. A behavioral stress test was given to premenopausal (n = 13) and postmenopausal women (n = 36). Biophysical and neuroendocrine responses were measured during and on completion of the stress test. The postmenopausal women were then randomized to placebo or transdermal estradiol treatment for 6 weeks, at which time another behavioral stress test was given. Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women (p &lt; 0.05). On retesting, significant biophysical responses that were present during the initial stress testing were still present (p &lt; 0.05) in the placebo group but were blunted with estrogen treatment. Plasma corticotropin, cortisol, androstenedione, and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women; this response was maintained after placebo treatment. Postmenopausal women treated with estrogen had blunted responses. Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women. The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women. Estrogen appears to blunt the stress-induced response.
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Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment... more
Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics. The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models. Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last...