Kim Juwon, Kim Jong-Won, Kim Yoonjung, Lee Kyung-A
Department of Laboratory Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Tumour Biol. 2014 Apr;35(4):3765-70. doi: 10.1007/s13277-013-1498-0. Epub 2013 Dec 11.
The aims of this study were to elucidate the association between RANTES-403 and an increased risk of gastric cancer in Korean males and to investigate the gene-gene interaction between IL-1B and RANTES. In total, 218 male patients with gastric cancer (114 diffuse types, 97 intestinal types, and 7 mixed types) and 377 male controls were included. RANTES-403 was genotyped, and age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression. A multifactor dimensionality reduction (MDR) test with three-way split interval validation confirmed by likelihood ratio and permutation analysis was carried out. A significant increase in the risk of gastric cancer for the intestinal-type group was observed for IL-1B-1464G carriers (OR = 2.535; 95% CI = 1.121-5.732; P = 0.02) as well as for those with IL-1B-1464 CG (OR = 2.342; 95% CI = 0.998-5.500; P = 0.05) or IL-1B-1464 GG (OR = 2.819; 95% CI = 1.170-6.793; P = 0.02). For the RANTES-403 genotype, there was no significant difference in the risk of gastric cancer between the overall gastric cancer and the control groups. When further stratified according to histological types, RANTES-403A carriers (OR = 1.743; 95% CI = 1.086-2.798; P = 0.021) or heterozygotes (OR = 1.791; 95% CI = 1.092-2.935; P = 0.021) showed increased risk for developing diffuse-type gastric cancer. MDR revealed a three-way locus-locus interaction between RANTES-403AA, IL-1B-1464GG, and IL-1B-511CT for diffuse-type gastric cancer in Korean males. We demonstrated that RANTES-403 was significantly associated with the risk of developing diffuse-type gastric cancer in men and found a possible gene-gene interaction between RANTES and IL-1B polymorphisms in gastric cancer carcinogenesis.
本研究的目的是阐明RANTES - 403与韩国男性胃癌风险增加之间的关联，并研究白细胞介素 - 1β（IL - 1B）和RANTES之间的基因 - 基因相互作用。总共纳入了218例男性胃癌患者（114例弥漫型、97例肠型和7例混合型）和377例男性对照。对RANTES - 403进行基因分型，并通过逻辑回归估计年龄调整后的比值比（OR）及95%置信区间（CI）。采用经似然比和置换分析确认的三向分割区间验证的多因素降维（MDR）测试。观察到对于肠型组，IL - 1B - 1464G携带者（OR = 2.535；95% CI = 1.121 - 5.732；P = 0.02）以及IL - 1B - 1464 CG（OR = 2.342；95% CI = 0.998 - 5.500；P = 0.05）或IL - 1B - 1464 GG（OR = 2.819；95% CI = 1.170 - 6.793；P = 0.02）的患者患胃癌的风险显著增加。对于RANTES - 403基因型，总体胃癌组和对照组之间患胃癌的风险无显著差异。当根据组织学类型进一步分层时，RANTES - 403A携带者（OR = 1.743；95% CI = 1.086 - 2.798；P = 0.021）或杂合子（OR = 1.791；95% CI = 1.092 - 2.935；P = 0.021）患弥漫型胃癌的风险增加MDR揭示了韩国男性弥漫型胃癌中RANTES - 403AA、IL - 1B - 1464GG和IL - 1B - 511CT之间的三向基因座 - 基因座相互作用。我们证明RANTES - 403与男性患弥漫型胃癌的风险显著相关，并发现RANTES和IL - 1B基因多态性在胃癌致癌过程中可能存在基因 - 基因相互作用。
