PO.PS01.07 · 人群科学

A body mass index polygenic risk score (PRS BMI ) and obesity-related cancer risk among women in the Hispanic Community Health Study/Study of Latinos

编号 3585 展板 3 时间 4/20 02:00–05:00 区域 Section 35 主讲 Humberto Parada, BS;MPH;PhD

分会场 Genetic Epidemiology 1: GxE, GWAS, Polygenic Risk Scores, and Post-GWAS

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作者与单位

Humberto Parada¹, Tamar Sofer², Margaret Pichardo³, Krista M. Perreira⁴, Laura Zhou⁵, Frank J. Penedo⁶, Amber Pirzada⁷, Martha Daviglus⁸, Gregory A. Talavera⁹, Linda C. Gallo⁹

¹School of Public Health, San Diego State University, San Diego, CA,²Department of Biostatistics, Harvard Medical School, Boston, MA,³Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA,⁴Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC,⁵Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC,⁶Department of Psychology, University of Miami, Coral Gables, FL,⁷College of Medicine, University of Illinois, Chicago, IL,⁸Department of Medicine, University of Illinois Chicago, Chicago, IL,⁹Department of Psychology, San Diego State University, San Diego, CA

摘要 Abstract

Background. Obesity is associated with an increased risk of cancer including cancers of the colon and rectum, endometrium, and breast among women. Polygenic risk scores (PRS), which sum the effects of risk variants, estimate an individual's genetic predisposition to complex phenotypic traits, such as obesity. We constructed a PRS for body mass index (PRS BMI ) and examined whether the PRS BMI was associated with the risk of obesity-related cancers (ORCs) among Hispanic/Latina women. We also examined whether BMI moderated or mediated the association between PRS BMI and ORC risk. Methods . This prospective cohort study included 8,380 Hispanic/Latina women (mean age at baseline=41.8±0.3 years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). At baseline in 2008-2011, height and weight were measured and used to compute BMI, and participants provided blood samples for genotyping. The PRS BMI was constructed using previously published weights downloaded from the polygenic score (PGS) catalog. The incidence of 13 obesity-related cancers diagnosed from baseline through 2021 was ascertained through linkages with four state cancer registries ( n =223 incident ORCs were diagnosed over a mean follow-up of 10.8 years). Survey multivariable Cox regression models estimated the associations (hazard ratios, HRs, and 95% confidence intervals, CIs) between the PRS BMI (per standard deviation, SD) and ORC risk overall and by BMI (<25 vs. ≥25 kg/m 2 ). Survey multivariable Cox regression and linear regression models tested the mediating effect of BMI (continuous, kg/m 2 ) on the association between PRS BMI (per SD) and ORC risk. Results. In stratified analyses, a 1-SD increase in the PRS BMI was associated with an ORC HR of 0.74 (95%CI=0.56-0.97) among women with BMI<30 kg/m 2 , but not among women with a BMI≥30 kg/m 2 (HR=0.95; 95%CI=0.68-1.33; P Interaction =0.15). In mediation analyses, PRS BMI was significantly associated with BMI (beta a =1.86; 95%CI=1.66-2.06); BMI was significantly associated with ORC risk, adjusting for PRS BMI (beta b =0.07; SE=0.01; HR=1.07; 95%CI=1.05-0.19); and BMI significantly mediated the association between PRS BMI and ORC risk (indirect effect, beta a *beta b =0.13; 95%CI=0.07-0.19). Conclusion . Genes predisposing women to a higher BMI may primarily impact ORC risk through BMI. These results highlight the importance of weight management for cancer prevention among Hispanic/Latina women.

利益披露 Disclosure

H. Parada, None.. T. Sofer, None.. M. Pichardo, None.. K. M. Perreira, None.. L. Zhou, None.. F. J. Penedo, None.. A. Pirzada, None.. M. Daviglus, None.. G. A. Talavera, None.. L. C. Gallo, None.

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