TEX15: A DNA repair gene associated with prostate cancer risk in Han Chinese

被引：9

作者：

Lin, Xiaoling ^{[1
,2
,3
]}

Chen, Zhongzhong ^{[3
]}

Gao, Peng ^{[1
,2
]}

Gao, Zhimei ^{[4
]}

Chen, Haitao ^{[5
]}

Qi, Jun ^{[6
]}

Liu, Fang ^{[1
,2
]}

Ye, Dingwei ^{[7
,8
]}

Jiang, Haowen ^{[1
,2
]}

Na, Rong ^{[1
,2
]}

Yu, Hongjie ^{[3
]}

Shi, Rong ^{[9
]}

Lu, Daru ^{[3
]}

Zheng, Siqun Lilly ^{[10
]}

Mo, Zengnan ^{[11
,12
]}

Sun, Yinghao ^{[13
]}

Ding, Qiang ^{[1
,2
]}

Xu, Jianfeng ^{[1
,2
]}

机构：

[1] Fudan Univ, Fudan Inst Urol, Huashan Hosp, Shanghai, Peoples R China

[2] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai, Peoples R China

[3] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Cent Lab, Shanghai, Peoples R China

[5] Fudan Univ, Sch Publ Hlth, Ctr Genom Translat Med & Prevent, Shanghai, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Urol, Shanghai, Peoples R China

[7] Fudan Univ, Shanghai Canc Ctr, Dept Urol, Shanghai, Peoples R China

[8] Fudan Univ, Dept Oncol, Shanghai Med Coll, Shanghai, Peoples R China

[9] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai, Peoples R China

[10] NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL USA

[11] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning, Guangxi Zhuang, Peoples R China

[12] Guangxi Med Univ, Dept Urol, Affiliated Hosp 1, Nanning, Guangxi Zhuang, Peoples R China

[13] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Urol, Shanghai, Peoples R China

来源：

PROSTATE | 2017年 / 77卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Chinese; DNA repair; exome array; genome-wide association study; prostate cancer; GENOME-WIDE ASSOCIATION; STRAND BREAK REPAIR; SUSCEPTIBILITY LOCI; CHROMOSOMAL SYNAPSIS; ANDROGEN RECEPTOR; VARIANTS; MUTATIONS; MLH3; RARE; MEN;

D O I：

10.1002/pros.23387

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundBoth common and rare genetic variants may contribute to risk of developing prostate cancer. Genome-wide association studies (GWASs) have identified approximate to 100 independent, common variants associated with prostate cancer risk. However, little is known about the association of rare variants (minor allele frequency [MAF] <1%) in the genome with prostate cancer risk. MethodsA two-stage study was used to test the association of rare, deleterious coding variants, annotated using predictive algorithms, with prostate cancer risk in Chinese men. Predicted rare, deleterious coding variants in the Illumina HumanExome-12 v1.1 beadchip were first evaluated in 1343 prostate cancer patients and 1008 controls. Significant variants were then validated in an additional 1816 prostate cancer patients and 1549 controls. ResultsIn the discovery stage, 14 predicted rare, deleterious coding variants were significantly associated with prostate cancer risk (P<0.01). In the confirmation stage, Q1631H in TEX15 (rs142485241), a DNA repair gene, was significantly associated with prostate cancer risk (P=0.0069). The estimated odds ratio (OR) of the variant in the combined analysis was 3.24 (95% Confidence Interval 1.85-6.06), P=8.81x10(-5). Additionally, rs28756990 (V741F) at MLH3 (P=0.06) and rs2961144 (I126V) at OR2A5 (P=0.065) were marginally associated with prostate cancer risk in the replication stage. ConclusionsOur study provided preliminary evidence that the rare variant Q1631H in DNA repair gene TEX15 is associated with prostate cancer risk. This finding complements known common prostate cancer risk-associated variants and suggests the possible role of DNA repair genes in prostate cancer development.

引用

页码：1271 / 1278

页数：8

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