Zhao Xue Ke, Mao Yi Min, Meng Hui, Song Xin, Hu Shou Jia, Lv Shuang, Cheng Rang, Zhang Tang Juan, Han Xue Na, Ren Jing Li, Qi Yi Jun, Wang Li Dong
Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Henan Key Laboratory of Cancer Epigenetic, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
PLoS One. 2017 May 18;12(5):e0177504. doi: 10.1371/journal.pone.0177504. eCollection 2017.
Cancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population.
A total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson's Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival.
Four of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107-1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100-1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098-1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089-1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with gender, TNM stage, histopathological type, smoking, family history and overall survival.
The present study identified four high-risk SNPs at 2q33 locus for Chinese lung cancer and demonstrated the shared susceptibility loci at 2q33 region for Chinese lung and esophageal cancers.
肺癌和食管癌是中国癌症相关死亡的主要原因，在组织学类型、危险因素和基因变异方面有许多相似之处。最近在中国食管癌患者中进行的全基因组关联研究（GWAS）已经证实了六个高风险候选单核苷酸多态性（SNP）。因此，本研究旨在确定这些SNP在中国人群中诱发肺癌的风险。
本研究从中国北方河南省食管癌高发地区招募了1170例肺癌患者和1530例正常受试者。采集所有受试者5毫升血液进行基因分型。使用TaqMan等位基因鉴别分析对从食管癌、肺癌和胃癌的全基因组关联研究（GWAS）中鉴定出的20个高风险SNP位点进行基因分型。使用χ2检验检查多态性是否偏离哈迪-温伯格平衡（HWE）。采用Bonferroni校正来校正20个与肺癌风险相关的SNP的统计学显著性。采用Pearson's χ2检验比较肺癌易感性基因型在性别、TNM分期、组织病理学类型、吸烟和家族史方面的分布。进行Kaplan-Meier和Cox回归分析以评估基因变异与总生存期之间 的关联。
在中国食管癌中被鉴定为高风险SNP的20个SNP中有4个显示中国肺癌风险增加, 其中包括rs3769823（OR = 1.26；95% CI = 1.107 - 1.509；P = 0.02）、rs10931936（OR = 1.283；95% CI = 1.100 - 1.495；P = 0.04）、rs2244438（OR = 1.294；95% CI = 1.098 - 1.525；P = 0.04）和rs13016963（OR = 1.268；95% CI = 1.089 - 1.447；P = 0.04）。所有这些SNP都位于2q33区域，该区域包含CASP8、ALS2CR12和TRAK2基因。然而，未观察到这些易感性SNP中的任何一个与性别、TNM分期、组织病理学类型、吸烟、家族史和总生存期有显著关联。
本研究鉴定出中国肺癌在2q33位点的四个高风险SNP，并证明了中国肺癌和食管癌在2q33区域存在共同的易感性位点。
