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Cancer Med ; 9(10): 3563-3573, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207560


BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

Cancer Epidemiol Biomarkers Prev ; 26(4): 587-596, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27908922


Background: Stomach cancer incidence shows substantial racial-ethnic disparity in the United States, with Korean Americans experiencing by far the highest incidence. We examined stomach cancer incidence trends in Korean Americans by tumor subsite, histology, and stage and compared them with incidence rates in racial-ethnic groups with the second highest rate (Japanese Americans) and the lowest rate (non-Hispanic whites; NHWs) as well as populations in South Korea and Japan.Methods: We calculated age-adjusted incidence rates by racial-ethnic groups, sex, and tumor characteristics, using the 1988-2012 California Cancer Registry data. Data on South Korea and Japan were obtained from the literature and other resources.Results: Between 1988 and 2012 in California, Korean Americans had about five times greater incidence than NHWs and twice that of Japanese Americans. Tumor characteristics differed by ethnic group and gender. The incidence in Korean Americans has declined during recent years, for both cardia and noncardia sites and for both intestinal- and diffuse-type histology. Although Korean Americans were diagnosed at an earlier stage than other Californians, the proportion with localized disease (43%) was much smaller than in South Korea (57%), where population-based screening is available.Conclusions: Stomach cancer incidence declined in the highest risk ethnic groups. However, the persistent disparity between Korean Americans and other racial-ethnic groups warrants additional strategies for prevention and earlier diagnosis.Impact: Analysis of California Cancer Registry data identified a racial-ethnic subgroup with stomach cancer disparity that may benefit from targeted prevention and screening efforts. Cancer Epidemiol Biomarkers Prev; 26(4); 587-96. ©2016 AACR.

Americanos Asiáticos/estatística & dados numéricos , Neoplasias Gástricas/epidemiologia , California/epidemiologia , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Japão/epidemiologia , Japão/etnologia , Masculino , Estadiamento de Neoplasias , Vigilância da População , República da Coreia/epidemiologia , República da Coreia/etnologia , Fatores de Risco , Distribuição por Sexo , Fumar/epidemiologia , Neoplasias Gástricas/etnologia
Cancer Causes Control ; 27(4): 527-43, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26898200


PURPOSE: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. METHODS: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. RESULTS: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. CONCLUSIONS: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.

Neoplasias da Mama/epidemiologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Adulto , Idoso , Animais , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Peixes , Humanos , Carne , Pessoa de Meia-Idade , Aves Domésticas , Carne Vermelha , Fatores de Risco
J Urol ; 194(2): 378-85, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25711194


PURPOSE: We assessed survival after radical prostatectomy, intensity modulated radiation therapy or conformal radiation therapy vs no local therapy for metastatic prostate cancer adjusting for patient comorbidity, androgen deprivation therapy and other factors. MATERIALS AND METHODS: We identified men 66 years old or older with metastatic prostate cancer treated with radical prostatectomy, intensity modulated radiation therapy, conformal radiation therapy or no local therapy in the SEER-Medicare linked database from 2004 to 2009. Multivariable Cox proportional hazards models before and after inverse propensity score weighting were used to assess all cause and prostate cancer specific mortality. Competing risk regression analysis was done to assess prostate cancer specific mortality. RESULTS: Of 4,069 men with metastatic prostate cancer radical prostatectomy in 47, intensity modulated radiation therapy in 88 and conformal radiation therapy in 107 were selected as local therapy vs no local therapy in 3,827. Radical prostatectomy was associated with a 52% decrease (HR 0.48, 95% CI 0.27-0.85) in the risk of prostate cancer specific mortality after adjusting for sociodemographics, primary tumor characteristics, comorbidity, androgen deprivation therapy and bone radiation within 6 months of diagnosis. Intensity modulated radiation therapy was associated with a 62% decrease (HR 0.38, 95% CI 0.24-0.61) in the risk of prostate specific cancer specific mortality. Conformal radiation therapy was not associated with improved survival compared to no local therapy. Propensity score weighting yielded comparable results. Competing risk analysis revealed a 42% and 57% decrease (SHR 0.58, 95% CI 0.35-0.95 and SHR 0.43, 95% CI 0.27-0.68, respectively) in the risk of prostate cancer specific mortality for radical prostatectomy and intensity modulated radiation therapy. CONCLUSIONS: Local therapy with radical prostatectomy and intensity modulated radiation therapy but not with conformal radiation therapy was associated with a survival benefit in men with metastatic prostate cancer. This finding warrants prospective evaluation in clinical trials.

Medicare , Prostatectomia/métodos , Neoplasias da Próstata/terapia , Medição de Risco , Programa de SEER , Idoso , Braquiterapia , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/secundário , Radioterapia Conformacional , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia