量化多种癌症类型之间的遗传相关性。
Quantifying the Genetic Correlation between Multiple Cancer Types.
机构信息
Department of Epidemiology, University of Washington, Seattle, Washington.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
出版信息
Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1427-1435. doi: 10.1158/1055-9965.EPI-17-0211. Epub 2017 Jun 21.
Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies. In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits. After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant ( < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, = 0.003), lung and colorectal cancer (rg = 0.31, = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, = 0.009), and colorectal and breast cancer (rg = 0.22, = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, = 1.03 × 10). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer. Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors. This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. .
许多癌症具有特定的遗传风险因素，包括通过全基因组关联研究（GWAS）确定的罕见高外显率突变和常见 SNP。然而，人们对癌症之间整体共享遗传率知之甚少。量化两种不同癌症之间遗传起源的程度，可以深入了解癌症的共同生物学机制，并为未来的遗传关联研究提供信息。在这项研究中，我们使用基于欧洲血统的 66958 例病例和 70665 例对照的特定于癌症的 GWAS 汇总统计数据，估计了六种癌症（乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌和前列腺癌）之间的两两遗传相关性。我们还估计了癌症与 14 种非癌症疾病和特征之间的遗传相关性。在调整了癌症之间 15 对遗传相关性测试后，我们发现胰腺癌和结直肠癌之间存在显著的（<0.003）遗传相关性（rg=0.55，=0.003），肺癌和结直肠癌之间存在显著的（<0.003）遗传相关性（rg=0.31，=0.001）。我们还发现肺癌和乳腺癌之间存在提示性遗传相关性（rg=0.27，=0.009），以及结直肠癌和乳腺癌之间存在提示性遗传相关性（rg=0.22，=0.01）。相比之下，我们没有发现前列腺癌与其他癌症有相当大的遗传率共享证据。在调整了癌症类型与其他特征之间的 84 项遗传相关性研究（Bonferroni 校正的 值：0.0006）后，只有肺癌和吸烟之间的遗传相关性仍然显著（rg=0.41，=1.03×10）。我们还观察到体重指数与除卵巢癌以外的所有癌症之间存在名义上显著的遗传相关性。我们的研究结果突出了新的遗传相关性，并支持了之前观察到癌症与危险因素之间存在关联的观察性研究。本研究表明癌症之间存在适度的遗传相关性；特别是，乳腺癌、结直肠癌和肺癌具有一定程度的遗传基础。
Zotero 插件