Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population

被引:79
作者
Dai, Juncheng [1 ,2 ]
Shen, Wei [1 ]
Wen, Wanqing [3 ]
Chang, Jiang [4 ,5 ,6 ,7 ]
Wang, Tongmin [8 ]
Chen, Haitao [9 ]
Jin, Guangfu [1 ,2 ]
Ma, Hongxia [1 ,2 ]
Wu, Chen [4 ,5 ]
Li, Lian [10 ]
Song, Fengju [10 ]
Zeng, Yixin [8 ]
Jiang, Yue [1 ]
Chen, Jiaping [1 ]
Wang, Cheng [1 ]
Zhu, Meng [1 ]
Zhou, Wen [1 ]
Du, Jiangbo [1 ]
Xiang, Yongbing [11 ]
Shu, Xiao-Ou [3 ]
Hu, Zhibin [1 ,2 ]
Zhou, Weiping [12 ]
Chen, Kexin [10 ]
Xu, Jianfeng [9 ]
Jia, Weihua [8 ]
Lin, Dongxin [4 ,5 ]
Zheng, Wei [3 ]
Shen, Hongbing [1 ,2 ]
机构
[1] Nanjing Med Univ, Sch Publ Hlth,Dept Epidemiol & Biostat, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Collaborat Innovat Ctr Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China
[3] Vanderbilt Univ, Med Ctr, Div Epidemiol,Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA
[4] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China
[5] Peking Union Med Coll, Beijing, Peoples R China
[6] Huazhong Univ Sci & Technol, Inst Occupat Med, Wuhan, Peoples R China
[7] Huazhong Univ Sci & Technol, Sch Publ Hlth, Key Lab Environm & Hlth, Minist Educ, Wuhan, Peoples R China
[8] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China
[9] Fudan Univ, Huashan Hosp, Fudan Inst Urol, Shanghai, Peoples R China
[10] Tianjin Med Univ, Canc Inst & Hosp, Key Lab Canc Prevent & Therapy Tianjin, Dept Epidemiol & Biostat,Natl Clin Res Ctr Canc, Tianjin, Peoples R China
[11] Shanghai Canc Inst, Shanghai, Peoples R China
[12] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
cancer; heritability; single-nucleotide polymorphisms; Chinese population; genome-wide complex trait analysis; COMPLEX TRAIT ANALYSIS; SUSCEPTIBILITY LOCI; OVARIAN-CANCER; EAST ASIANS; MISSING HERITABILITY; GENETIC ARCHITECTURE; LARGE PROPORTION; FAMILIAL RISK; SNPS EXPLAIN; IDENTIFIES;
D O I
10.1002/ijc.30447
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWASs) have identified a number of common single-nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (LC) (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for hepatitis B virusrelated hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250 kb or 500 kb upward and downward of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for LC (R-2 = 0.641, p = 0.001) and esophageal squamous cell cancer (R-2 = 0.633, p = 0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese.
引用
收藏
页码:329 / 336
页数:8
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