Arisawa Tomiyasu, Tahara Tomomitsu, Shibata Tomoyuki, Nagasaka Mitsuo, Nakamura Masakatsu, Kamiya Yoshio, Fujita Hiroshi, Yoshioka Daisuke, Arima Yuko, Okubo Masaaki, Hirata Ichiro, Nakano Hiroshi, De la Cruz Vidal
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan.
Oncol Rep. 2008 Jan;19(1):223-8.
The macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. Two functional polymorphisms have been identified in the promoter region of the MIF gene. We attempted to clarify the associations of these polymorphisms with the development of gastric cancer. The study was performed in 229 patients with gastric cancer and 428 subjects with no evidence of gastric malignancies on the upper gastro-duodenal endoscopy. The severity of histological chronic gastritis was classified according to the updated Sydney system. Overall, the 5-CATT carriers had a reduced risk of developing gastric cancer (OR, 0.67; 96% CI, 0.48-0.93; p=0.015), especially the diffuse type cancer. In subjects >60 years, the adjusted risk for gastric cancer among individuals who were -173C carriers was 1.71 (range, 1.03-2.84; p=0.038) compared to the G/G homozygous genotype. The number of 7-CATT alleles was also positively correlated with the development of intestinal type gastric cancer (adjusted OR, 1.70; 95% CI, 1.02-2.58; p=0.043). In subjects <60 years, the 7/7-CATT homozygous genotype was linked with a risk for the progression of atrophic gastritis (adjusted OR, 8.74; 95% CI, 1.31-58.6; p=0.026). In addition, the number of 7-CATT alleles was significantly correlated with the activity and inflammation scores (p=0.010 and 0.030, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene are associated with the progression of gastric mucosal inflammation and the development of mucosal atrophy at an early stage in life and these genotypes may increase the risk for the subsequent development of gastric cancer, especially the intestinal type, in older subjects.
巨噬细胞移动抑制因子（MIF）是一种关键的促炎介质。在MIF基因的启动子区域已鉴定出两种功能性多态性。我们试图阐明这些多态性与胃癌发生之间的关联。该研究纳入了229例胃癌患者和428例经上消化道十二指肠内镜检查未发现胃恶性肿瘤迹象的受试者。根据更新后的悉尼系统对组织学慢性胃炎的严重程度进行分类。总体而言，携带5-CATT的个体患胃癌的风险降低（比值比[OR]，0.67；96%可信区间[CI]，0.48 - 0.93；p = 0.015），尤其是弥漫型癌症。在年龄大于60岁的受试者中，与G/G纯合基因型相比，-173C携带者患胃癌的校正风险为1.71（范围，1.03 - 2.84；p = 0.038）。7-CATT等位基因的数量也与肠型胃癌的发生呈正相关（校正OR，1.70；95%CI，1.02 - 2.58；p = 0.043）。在年龄小于60岁的受试者中，7/7-CATT纯合基因型与萎缩性胃炎进展风险相关（校正OR，8.74；95%CI，1.31 - 58.6；p = 0.026）。此外，7-CATT等位基因的数量与活动度和炎症评分显著相关（分别为p = 0.010和0.030）。我们的结果表明，MIF基因启动子的功能性多态性与胃黏膜炎症的进展以及生命早期黏膜萎缩的发生相关，并且这些基因型可能会增加老年受试者后续发生胃癌尤其是肠型胃癌的风险。
