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多民族印度尼西亚人群结直肠癌的遗传风险因素。

Genetic risk factors for colorectal cancer in multiethnic Indonesians.

机构信息

Faculty Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.

Mochtar Riady Institute for Nanotechnology, Pelita Harapan University, Tangerang, Banten, Indonesia.

出版信息

Sci Rep. 2021 May 11;11(1):9988. doi: 10.1038/s41598-021-88805-4.

DOI:10.1038/s41598-021-88805-4
PMID:33976257
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8113452/
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.

摘要

结直肠癌是印度尼西亚常见的癌症,但在资源有限的情况下,对其研究较少。我们进行了一项全基因组关联研究,重点评估和初步发现印度尼西亚人结直肠癌的风险因素。我们对印度尼西亚望加锡的 162 例结直肠癌病例进行了详细的问卷调查和血液样本采集。我们还建立了一个由 193 名健康个体组成的对照组,按年龄、性别和种族进行频率匹配。对 84 例病例和 89 例通过质量控制的对照进行全基因组关联分析。我们使用逻辑回归评估了已知的结直肠癌遗传变异,并使用贝叶斯变量选择技术建立了全基因组多基因风险模型。我们复制了染色体 6 上 rs9497673、rs6936461 和 rs7758229、染色体 10 上 rs11255841 以及染色体 15 上 rs4779584、rs11632715 和 rs73376930 的关联。多基因建模确定了 10 个与结直肠癌风险相关的 SNP。这项工作有助于描述 SCL22A3、SCG5、GREM1 和 STXBP5-AS1 基因中的变异与印度尼西亚多样化人群结直肠癌之间的关系。随着生物银行和国际研究合作的进一步发展,将确定印度尼西亚人结直肠癌风险的特定变异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/f89f98acd6dd/41598_2021_88805_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/d6ac7ced3f3d/41598_2021_88805_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/9fda76abc337/41598_2021_88805_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/d09f4ea5e96f/41598_2021_88805_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/c44dcf6e9e5a/41598_2021_88805_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/f89f98acd6dd/41598_2021_88805_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/d6ac7ced3f3d/41598_2021_88805_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/9fda76abc337/41598_2021_88805_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/d09f4ea5e96f/41598_2021_88805_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/c44dcf6e9e5a/41598_2021_88805_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1414/8113452/f89f98acd6dd/41598_2021_88805_Fig5_HTML.jpg

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