Dai Juncheng, Shen Wei, Wen Wanqing, Chang Jiang, Wang Tongmin, Chen Haitao, Jin Guangfu, Ma Hongxia, Wu Chen, Li Lian, Song Fengju, Zeng YiXin, Jiang Yue, Chen Jiaping, Wang Cheng, Zhu Meng, Zhou Wen, Du Jiangbo, Xiang Yongbing, Shu Xiao-Ou, Hu Zhibin, Zhou Weiping, Chen Kexin, Xu Jianfeng, Jia Weihua, Lin Dongxin, Zheng Wei, Shen Hongbing
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Int J Cancer. 2017 Jan 15;140(2):329-336. doi: 10.1002/ijc.30447. Epub 2016 Oct 11.
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 virus-related 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 = 0.641, p = 0.001) and esophageal squamous cell cancer (R = 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.
家族聚集性表明癌症风险具有遗传性。近期的全基因组关联研究(GWAS)已经鉴定出许多常见的单核苷酸多态性(SNP)。后续的遗传力分析表明,SNP可以解释高加索人群中不同癌症表型的适度变异。然而,在中国人群中相关信息较少。我们对中国人群中九个解剖部位的常见癌症进行了全基因组复杂性状分析(14629例癌症病例与17554例对照),并基于常见SNP估计了这些癌症的遗传力。我们发现,常见SNP对所有九个癌症部位都解释了一定程度的遗传力且具有显著性:胃癌(20.26%)、食管鳞状细胞癌(19.86%)、结直肠癌(16.30%)、肺癌(LC)(15.17%)、上皮性卵巢癌(13.31%),以及与乙型肝炎病毒相关的肝细胞癌、前列腺癌、乳腺癌和鼻咽癌的遗传力相似,约为10%。我们发现,去除GWAS报告的SNP上下游250 kb或500 kb扩展区域时,显示出近25%或小于25%的变化。我们还发现,仅对于LC(R = 0.641,p = 0.001)和食管鳞状细胞癌(R = 0.633,p = 0.002),每条染色体划分的变异与染色体长度之间存在强线性相关性,这向我们暗示了癌症的复杂异质性。这些结果表明中国人群中九种常见癌症的多基因遗传结构。应进一步努力发现中国人中不同癌症类型隐藏的遗传力。