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1.
Am J Epidemiol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31504108

RESUMO

Previous studies have suggested a "J-shaped" relationship between body mass index (BMI, kg/m2) and survival among head and neck cancer (HNC) patients. However, BMI is a vague measure of body composition. To provide greater resolution we used Bayesian sensitivity analysis, informed by external data, to model the relationship between predicted fat mass index (FMI, kg adipose tissue/m2), lean mass index (LMI, kg lean tissue/m2) and survival. We estimated posterior median hazard ratios (HR) and 95% credible intervals for the BMI-mortality relationship in a Bayesian framework using data from 1,180 adults in North Carolina with HNC diagnosed between 2002 and 2006. Risk factors were assessed by interview shortly after diagnosis and vital status through 2013 via the National Death Index. The relationship between BMI and all-cause mortality was convex with a nadir at 28.6 with greater risk observed throughout the normal weight range. The sensitivity analysis indicated that this was consistent with opposing increases in risk with FMI (1 kg/m2 increase, HR = 1.04 [1.00, 1.08]) and decreases with LMI (1 kg/m2 increase, HR = 0.90 [0.85, 0.95]). Patterns were similar for HNC-specific mortality but associations were stronger. Measures of body composition, rather than BMI, should be considered in relation to mortality risk.

2.
Am J Hum Genet ; 105(3): 658-668, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31474320

RESUMO

Neuroblastoma is a cancer of the developing sympathetic nervous system. It is diagnosed in 600-700 children per year in the United States and accounts for 12% of pediatric cancer deaths. Despite recent advances in our understanding of this malignancy's complex genetic architecture, the contribution of rare germline variants remains undefined. Here, we conducted a genome-wide analysis of large (>500 kb), rare (<1%) germline copy number variants (CNVs) in two independent, multi-ethnic cohorts totaling 5,585 children with neuroblastoma and 23,505 cancer-free control children. We identified a 550-kb deletion on chromosome 16p11.2 significantly enriched in neuroblastoma cases (0.39% of cases and 0.03% of controls; p = 3.34 × 10-9). Notably, this CNV corresponds to a known microdeletion syndrome that affects approximately one in 3,000 children and confers risk for diverse developmental phenotypes including autism spectrum disorder and other neurodevelopmental disorders. The CNV had a substantial impact on neuroblastoma risk, with an odds ratio of 13.9 (95% confidence interval = 5.8-33.4). The association remained significant when we restricted our analysis to individuals of European ancestry in order to mitigate potential confounding by population stratification (0.42% of cases and 0.03% of controls; p = 4.10 × 10-8). We used whole-genome sequencing (WGS) to validate the deletion in paired germline and tumor DNA from 12 cases. Finally, WGS of four parent-child trios revealed that the deletion primarily arose de novo without maternal or paternal bias. This finding expands the clinical phenotypes associated with 16p11.2 microdeletion syndrome to include cancer, and it suggests that disruption of the 16p11.2 region may dysregulate neurodevelopmental pathways that influence both neurological phenotypes and neuroblastoma.

3.
Cancer ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31398265

RESUMO

BACKGROUND: After controlling for baseline disease factors, researchers have found that black women have worse breast cancer survival, and this suggests that treatment differences may contribute to poorer outcomes. Delays in initiating and completing treatment are one proposed mechanism. METHODS: Phase 3 of the Carolina Breast Cancer Study involved a large, population-based cohort of women with incident breast cancer. For this analysis, we included black women (n = 1328) and white women (n = 1331) with stage I to III disease whose treatment included surgery with or without adjuvant therapies. A novel treatment pathway grouping was used to benchmark the treatment duration (surgery only, surgery plus chemotherapy, surgery plus radiation, or all 3). Models controlled for the treatment pathway, age, and tumor characteristics and for demographic factors related to health care access. Exploratory analyses of the association between delays and cancer recurrence were performed. RESULTS: In fully adjusted analyses, blacks had 1.73 times higher odds of treatment initiation more than 60 days after their diagnosis in comparison with whites (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.04-2.90). Black race was also associated with a longer treatment duration. Blacks were also more likely to be in the highest quartile of treatment duration (OR, 1.69; 95% CI, 1.41-2.02), even after adjustments for demographic and tumor characteristics (OR, 1.31; 95% CI, 1.04-1.64). A nonsignificant trend toward a higher recurrence risk was observed for patients with delayed initiation (hazard ratio, 1.44; 95% CI, 0.89-2.33) or the longest duration (hazard ratio, 1.17; 95% CI, 0.87-1.59). CONCLUSIONS: Black women more often had delayed treatment initiation and a longer duration than whites receiving similar treatment. Interventions that target access barriers may be needed to improve timely delivery of care.

4.
Am J Med Genet A ; 179(9): 1846-1856, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313509

RESUMO

Primary congenital glaucoma (PCG) is a rare but serious birth defect. Genetic mutations have been implicated in the development of PCG, but little is known about nongenetic risk factors. This study investigates potential risk factors for PCG in the National Birth Defects Prevention Study (NBDPS), a large population-based case-control study of major birth defects in the United States. The analysis includes case infants with PCG (N = 107) and control infants without birth defects (N = 10,084) enrolled in NBDPS from birth years 2000-2011. Pregnancy/infant clinical characteristics, demographics, and parental health history were collected through maternal interview. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to examine associations with all PCG cases and isolated PCG cases without other major malformations. Associations with all the cases included term low birth weight (<2,500 g; aOR = 2.80, CI 1.59-4.94), non-Hispanic black maternal race/ethnicity (aOR = 2.42, CI 1.42-4.13), maternal history of seizure (aOR = 2.73, CI 1.25-5.97), maternal antihypertensive use (aOR = 3.60, CI 1.52-8.53), and maternal sexually transmitted infection (aOR = 2.75, CI 1.17-6.44). These factors were also associated with isolated PCG, as was maternal use of nonsteroidal anti-inflammatory drugs (aOR = 2.70, CI 1.15-6.34). This study is among the first to examine a wide array of potential risk factors for PCG in a population-based sample.

5.
Birth Defects Res ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31322328

RESUMO

OBJECTIVE: To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). RESULTS: Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). CONCLUSION: The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

6.
Cancer Epidemiol ; 61: 165-171, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279991

RESUMO

BACKGROUND: There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake. METHODS: The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 case-parent sets through the Children's Oncology Group's Childhood Cancer Research Network. We ascertained dietary nutrient intake through questionnaires and genotyped 463 SNPs in vitamin A-related genes from saliva DNA. Offspring and maternal log-additive risk ratios (RR) and stratum-specific RR for gene-environment interaction were estimated with a log-linear model. We avoided false positives due to multiple testing by using the false discovery rate (FDR). RESULTS: When all neuroblastoma cases were considered together, no offspring variants met the significance criteria (FDR Q-value < 0.2). One maternal SNP (rs12442054) was associated with decreased risk of neuroblastoma (RR: 0.61; 95% Confidence Interval (CI): 0.47-0.79, Q = 0.076). When the cases were categorized according to prognostic risk category and age at onset, nine offspring SNPs were significantly associated with intermediate-risk neuroblastoma. Maternal rs6776706 was associated with (RR: 0.49; 95% CI: 0.33-0.72, Q = 0.161) high-risk neuroblastoma and maternal rs11103603 (RR: 0.60; 95% CI: 0.45-0.79, Q = 0.127) was associated with neuroblastoma aged <1 year. For gene-environment interaction, maternal rs729147 was associated with decreased risk of neuroblastoma among mothers with vitamin A consumption above the recommendation. CONCLUSIONS: Although there is biologic plausibility for the role of vitamin A in neuroblastoma, we found weak evidence of a relationship between vitamin A related genes and neuroblastoma.

7.
Birth Defects Res ; 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31328417

RESUMO

BACKGROUND: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens. METHODS: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA. RESULTS: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol. CONCLUSIONS: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers.

9.
Oral Oncol ; 94: 47-57, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178212

RESUMO

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

10.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1417-1426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31209147

RESUMO

BACKGROUND: Few studies have examined noncancer outcomes among patients diagnosed with cancer as adolescents and young adults (AYA). We examined risk of mortality from noncancer causes after an AYA cancer diagnosis and investigated disparities according to race/ethnicity and other characteristics. METHODS: Patients with a first primary cancer at ages 15 to 39 years diagnosed during 1987 to 2015 were identified in the Surveillance, Epidemiology, and End Results database (N = 242,940 women, 158,347 men). Survival months were accrued from diagnosis until death or December 2015. Multivariable-adjusted HRs were used to examine disparities in mortality from all noncancer causes, cardiovascular diseases (CVD), and infectious diseases (ID) according to race/ethnicity, geographic region, and county-level characteristics. RESULTS: For all cancer types combined, the 10-year cumulative incidence of noncancer-related death after AYA cancer was 2% and 5% among women and men, respectively. With adjustment for cancer type, all noncancer mortality was increased among non-Hispanic Black AYAs [HR vs. non-Hispanic White: HRWomen = 2.31; 95% confidence interval (CI): 2.16-2.47; HRMen = 2.17; 95% CI: 2.05-2.30] and those in the South (HR vs. Northeast: HRWomen = 1.18; 95% CI: 1.07-1.29; HRMen = 1.42; 95% CI: 1.31-1.55) or in rural counties (HR vs. metro: HRWomen = 1.74; 95% CI: 1.47-2.07; HRMen = 1.57; 95% CI: 1.33-1.86). Mortality from CVD and ID was also elevated among non-Hispanic Black AYAs. CONCLUSIONS: Results of this study suggest that noncancer mortality after AYA cancer is highest among survivors who are non-Hispanic Black or live in the South or in rural counties. IMPACT: Our analyses highlight disparities among AYAs with cancer and identify subgroups that may be targeted for increased medical surveillance or behavioral interventions.

11.
Neurotoxicology ; 73: 150-160, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951742

RESUMO

Organophosphate esters (OPEs) are commonly used as plasticizers and flame retardants in consumer products, and exposure is relatively ubiquitous in most populations studied. This may be of concern as some OPEs may be neurotoxic, endocrine-disrupting, and interfere with behavioral development; however, observational evidence is limited. We used data from the Pregnancy, Infection, and Nutrition Study, a prospective birth cohort study, to investigate associations between maternal OPE metabolite concentrations during pregnancy and behavioral development in offspring. Women provided a urine sample during pregnancy that was analyzed for concentrations of OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). Offspring's behavioral development was assessed by the Behavioral Assessment System for Children (2nd Edition) (BASC-2) at approximately 36 months. Linear regression was used to estimate associations between tertiles in specific gravity-corrected OPE metabolite concentrations and children's scores on the BASC-2, adjusted for maternal age, maternal BMI, maternal race, maternal education, familial income, maternal depression, quality of the home environment, and sex. Higher BDCIPP concentrations were associated with higher scores on the Behavioral Symptoms Index (1st vs. 3rd tertile: ß = 3.03; 95% CI = 0.40, 5.67) and Externalizing Problems (1st vs. 3rd tertile: ß = 2.49; 95% CI: -0.12, 5.10) composites. Among BASC-2 scales, BDCIPP was most strongly associated with Withdrawal, Attention Problems, Depression, Hyperactivity, and Aggression. DPHP concentrations were also associated with higher scores on the Externalizing Problems and Behavioral Symptoms Index composites, but not as strongly as BDCIPP. Conversely, higher concentrations of ip-PPP were associated with fewer adverse behavioral symptoms, including an inverse association with the Internalizing Problems composite (1st vs. 3rd tertile: ß = -3.74; 95% CI = -6.75, -0.74) and constituent scales. BCIPHIPP was not strongly associated with any measured behavioral outcomes. Our results suggest that greater maternal exposure to tris(1,3-dichloro-2-propyl phosphate) (TDCIPP, parent compound of BDCIPP) and, to a lesser degree, triphenyl phosphate (TPHP, parent compound of DPHP) during pregnancy is associated with adverse behavioral development in children. Our study contributes to the growing body of evidence pertaining to adverse developmental effects of prenatal OPE exposure and highlights the need for further research to characterize risks associated with this ubiquitous family of chemicals.

12.
Int J Pediatr Otorhinolaryngol ; 122: 18-26, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30928866

RESUMO

OBJECTIVE: Anotia and microtia are congenital malformations of the external ear with few known risk factors. We conducted a comprehensive assessment of a wide range of potential risk factors using data from the National Birth Defects Prevention Study (NBDPS), a population-based case-control study of non-chromosomal structural birth defects in the United States. METHODS: Mothers of 699 infants with anotia or microtia (cases) and 11,797 non-malformed infants (controls) delivered between 1997 and 2011 were interviewed to obtain information about sociodemographic, health behavioral, and clinical characteristics. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated with logistic regression. RESULTS: Infants with anotia/microtia were more likely to be male (aOR, 1.29; 95% CI, 1.10-1.50) and from a multifetal pregnancy (aOR, 1.68; 95% CI, 1.16-2.42). Cases were also more likely to have parents of Hispanic ethnicity (maternal aOR, 3.19; 95% CI, 2.61-3.91; paternal aOR, 2.11; 95% CI, 1.54-2.88), and parents born outside the United States (maternal aOR, 1.29; 95% CI, 1.06-1.57; paternal aOR, 1.92; 95% CI, 1.53-2.41). Maternal health conditions associated with increased odds of anotia/microtia included obesity (aOR, 1.31; 95% CI, 1.06-1.61) and pre-pregnancy diabetes (type I aOR, 9.89; 95% CI, 5.46-17.92; type II aOR, 4.70; 95% CI, 2.56-8.63). Reduced odds were observed for black mothers (aOR, 0.57; 95% CI, 0.38-0.85) and mothers reporting daily intake of folic acid-containing supplements (aOR, 0.59; 95% CI, 0.46-0.76). CONCLUSION: We identified several risk factors for anotia/microtia, some which have been previously reported (e.g., diabetes) and others which we investigate for perhaps the first time (e.g., binge drinking) that warrant further investigation. Our findings point to some potentially modifiable risk factors and provide further leads toward understanding the etiology of anotia/microtia.


Assuntos
Microtia Congênita/epidemiologia , Diabetes Mellitus/epidemiologia , Adulto , Afro-Americanos/estatística & dados numéricos , Estudos de Casos e Controles , Microtia Congênita/etnologia , Suplementos Nutricionais , Orelha Externa/anormalidades , Pai/estatística & dados numéricos , Feminino , Ácido Fólico/uso terapêutico , Comportamentos Relacionados com a Saúde , Hispano-Americanos/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Obesidade/epidemiologia , Gravidez , Gravidez Múltipla , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
13.
Cancer ; 125(12): 2107-2114, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30892701

RESUMO

BACKGROUND: Relative to the general population, cancer patients and survivors may have an elevated risk of mortality from noncancer causes, such as cardiovascular disease and infections, but few studies have examined rates of noncancer mortality among patients diagnosed as adolescents and young adults (AYAs) (ages 15-39 years). METHODS: The Surveillance, Epidemiology, and End Results database was used to identify AYA patients who were diagnosed with a first malignant cancer between 1973 and 2015. Rates of mortality from noncancer causes among AYAs with cancer were compared with those in the general US population using standardized mortality ratios (SMRs), adjusted for age, sex, race, and calendar year. RESULTS: Among 235,541 AYAs with cancer, a total of 12,948 deaths from noncancer causes occurred over 3.1 million total person-years of follow-up. Overall, noncancer mortality was significantly increased among AYAs with cancer relative to the general population (SMR, 1.84; 95% CI, 1.80-1.87). SMRs were particularly elevated for infectious diseases (SMR, 5.13; 95% CI, 4.95-5.32), cardiovascular disease (SMR, 1.55; 95% CI, 1.50-1.60), and renal diseases (SMR, 2.40; 95% CI, 2.12-2.71). These associations persisted for more than 20 years after cancer diagnosis. Cancer types associated with the highest SMRs for all noncancer mortality included leukemias (SMR, 5.26), Hodgkin lymphoma (SMR, 3.12), non-Hodgkin lymphoma (SMR, 6.33), central nervous system tumors (SMR, 3.38), head and neck cancers (SMR, 2.09), and cervical/uterine cancers (SMR, 2.03). CONCLUSIONS: AYAs with cancer have an elevated burden of mortality from noncancer causes that persists many years after cancer diagnosis, highlighting the importance of comprehensive, long-term follow-up care for noncancer conditions throughout survivorship.

14.
Am J Epidemiol ; 188(5): 814-817, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877290

RESUMO

In 2018, the Society for Epidemiologic Research and its partner journal, the American Journal of Epidemiology, assembled a working group to develop a set of papers devoted to the "future of epidemiology." These 14 papers covered a wide range of topic areas and perspectives, from thoughts on our profession, teaching, and methods to critical areas of substantive research. The authors of those papers considered current challenges and future opportunities for research and education. In light of past commentaries, 4 papers also include reflections on the discipline at present and in the future.

15.
Oral Oncol ; 89: 115-120, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732948

RESUMO

OBJECTIVE: There is considerable variation in the travel required for a patient with head and neck squamous cell carcinoma (HNSCC) to receive a diagnosis. The impact of this travel on the late diagnosis of cancer remains unexamined, even though presenting stage is the strongest predictor of mortality. Our aim is to determine whether travel time affects HNSCC stage at diagnosis independently of other risk factors, and whether this association is affected by socioeconomic status. MATERIALS AND METHODS: Cases were obtained from the CHANCE database, a population-based case-control study in North Carolina (n = 808). The mean age was 59.6 and 72% were male. Stage at diagnosis was categorized as early (T1-T2) or advanced (T3-T4) T stage and the presence or absence of nodal metastasis. Multivariate logistic regression models were used to estimate odds ratios for stage-at-diagnosis based on travel time, after adjustment for variables including demographics, income, insurance status, alcohol, and tobacco use. RESULTS: The adjusted odds ratio (OR) of advanced T-stage at diagnosis was 1.97 for each hour driven (95% CI 1.36-2.87). There was no association with nodal metastases. There was a significant interaction between travel time and income (p = 0.026) with a pattern of higher ORs for increased distance among lower income (<$20,000) patients compared to the ORs for higher income (>$20,000) patients. DISCUSSION: Travel time was an independent contributor to advanced T stage at diagnosis among low income patients. This suggests travel burden may be a barrier to early diagnosis of HNSCC for impoverished patients.

16.
Environ Int ; 125: 161-171, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716576

RESUMO

OBJECTIVES: To examine plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) in association with survival among women with breast cancer who participated in a population-based case-control study. METHODS: Participants included 456 white and 292 black women from the Carolina Breast Cancer Study Phase I who were diagnosed with primary invasive breast cancer from 1993 to 1996, and who had available DDE/DDT and lipid measurements from blood samples obtained on average 4.1 months after diagnosis. Using the National Death Index, we identified 392 deaths (210 from breast cancer) over a median follow-up of 20.6 years. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific 5-year mortality, and 20-year mortality conditional on 5-year survival, for lipid-standardized DDE and DDT levels. Associations stratified by race and estrogen receptor (ER) status were also examined. RESULTS: The highest versus lowest DDE tertile and the highest vs non-detectable DDT quantile were associated with HRs of 1.95 (95% CI = 1.31-2.92) and 1.64 (95% CI = 1.10-2.44), respectively, for 20-year conditional all-cause mortality. DDE levels above versus below the median were associated with a HR of 1.69 (95% CI = 1.06-2.68) for 20-year conditional breast cancer-specific mortality among women overall, and HRs were 2.36 (95% CI = 1.03-5.42) among black women and 1.57 (95% CI = 0.86-2.89) among white women (PInteraction = 0.42), and 3.24 (95% CI = 1.38-7.58) among women with ER- tumors and 1.29 (95% CI = 0.73-2.28) among women with ER+ tumors (PInteraction = 0.03). CONCLUSION: Exposure to DDE/DDT may adversely impact overall and breast cancer-specific survival. DDE exposure may contribute to the racial disparities in breast cancer survival.

17.
PLoS One ; 14(1): e0211488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682163

RESUMO

PURPOSE: Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A lesions. METHODS: We conducted a case-control analysis using data from the Carolina Breast Cancer Study (1993-2001). Analyses were restricted to Luminal A tumors and screen-detected tumors among mammography-eligible women, to limit confounding by mode of detection (N = 108 DCIS; N = 203 invasive). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between risk factors and lesion type. RESULTS: In stratified analyses, we observed qualitative differences in the direction of association for ever smoking, obese BMI, high waist-to-hip-ratio (WHR), and ≥10 years of oral contraceptive use between DCIS and invasive disease. Breastfeeding was inversely associated with invasive disease and was not associated with DCIS. Interaction tests for risk factor associations between Luminal A DCIS and invasive breast cancer were not statistically significant (p>0.05). CONCLUSIONS: Among Luminal A tumors, established breast cancer risk factors may exert stronger effects on progression of early lesions to invasive disease, with lesser effects on risk of DCIS.

18.
Cancer Epidemiol ; 59: 8-14, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30640041

RESUMO

PURPOSE: A recent study using national data from 2000 to 2009 identified colorectal cancer (CRC) mortality "hotspots" in 11 counties of North Carolina (NC). In this study, we used more recent, state-specific data to investigate the county-level determinants of geographic variation in NC through a geospatial analytic approach. METHOD: Using NC CRC mortality data from 2003 to 2013, we first conducted clustering analysis to confirm spatial dependence. Spatial economic models were then used to incorporate spatial structure to estimate the association between determinants and CRC mortality. We included county-level data on socio-demographic characteristics, access and quality of healthcare, behavioral risk factors (CRC screening, obesity, and cigarette smoking), and urbanicity. Due to correlation among screening, obesity and quality of healthcare, we combined these factors to form a cumulative risk group variable in the analysis. RESULTS: We confirmed the existence of spatial dependence and identified clusters of elevated CRC mortality rates in NC counties. Using a spatial lag model, we found significant interaction effect between CRC risk groups and socioeconomic deprivation. Higher CRC mortality rates were also associated with rural counties with large towns compared to urban counties. CONCLUSION: Our findings depicted a spatial diffusion process of CRC mortality rates across NC counties, demonstrated intertwined effects between SES deprivation and behavioral risks in shaping CRC mortality at area-level, and identified counties with high CRC mortality that were also deprived in multiple factors. These results suggest interventions to reduce geographic variation in CRC mortality should develop multifaceted strategies and work through shared resources in neighboring areas.

19.
Cancer Causes Control ; 30(1): 31-39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30617775

RESUMO

BACKGROUND: The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype. METHODS: Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808). RESULTS: Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242). CONCLUSIONS: While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Grupos de Populações Continentais , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
20.
Laryngoscope ; 2019 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-30637762

RESUMO

OBJECTIVES/HYPOTHESIS: Literature examining long-term survival in head and neck squamous cell carcinoma (HNSCC) with human papillomavirus (HPV) status is lacking. We compare 10-year overall survival (OS) rates for cases to population-based controls. STUDY DESIGN: Prospective cohort study. METHODS: Cases surviving 5 years postdiagnosis were identified from the Carolina Head and Neck Cancer Study. We examined 10-year survival by site, stage, p16, and treatment using Kaplan-Meier and Cox proportional hazard models. Cases were compared to age-matched, noncancer controls with stratification by p16 and smoking status. RESULTS: Ten-year OS for HNSCC is less than controls. In 581 cases, OS differed between sites with p16+ oropharynx having the most favorable prognosis (87%), followed by oral cavity (69%), larynx (67%), p16- oropharynx (56%), and hypopharynx (51%). Initial stage, but not treatment, also impacted OS. When compared to controls matched on smoking status, the hazard ratio (HR) for death in p16+ oropharynx cases was 1.5 (95% confidence interval [CI]: 0.7-3.1) for smokers and 2.4 (95% CI: 0.7-8.8) for nonsmokers. Similarly, HR for death in non-HPV-associated HNSCC was 2.2 (95% CI: 1.7-3.0) for smokers and 2.4 (95% CI: 1.4-4.9) for nonsmokers. CONCLUSIONS: OS for HNSCC cases continues to decrease 5 years posttreatment, even after stratification by p16 and smoking status. Site, stage, smoking, and p16 status are significant factors. These data provide important prognostic information for HNSCC. LEVEL OF EVIDENCE: 2 Laryngoscope, 2019.

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