Genetic risk factors for colorectal cancer in multiethnic Indonesians

印度尼西亚多民族人群结肠直肠癌的遗传风险因素

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作者:Irawan Yusuf #, Bens Pardamean #, James W Baurley #, Arif Budiarto, Upik A Miskad, Ronald E Lusikooy, Arham Arsyad, Akram Irwan, George Mathew, Ivet Suriapranata, Rinaldy Kusuma, Muhamad F Kacamarga, Tjeng W Cenggoro, Christopher McMahan, Chase Joyner, Carissa I Pardamean

Abstract

Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

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