Kato S, Onda M, Matsukura N, Tokunaga A, Matsuda N, Yamashita K, Shields P G
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Biomed Pharmacother. 1997;51(4):145-9. doi: 10.1016/s0753-3322(97)85581-3.
The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.
胃癌的发生是一个多步骤、多因素的过程。幽门螺杆菌感染、胃萎缩与胃癌之间的关联最近受到了关注。本研究的目的是通过使用分子流行病学技术来阐明胃癌的危险因素，这些技术涉及遗传易感性、胃萎缩以及包括幽门螺杆菌感染在内的血清标志物。我们采用了年龄和性别匹配的病例对照研究，以患有良性胃部病变的患者作为对照。低血清胃蛋白酶原I水平（临界值<50 ng/mL）和低胃蛋白酶原I/胃蛋白酶原II比值（临界值<3.0）与胃癌风险显著相关（比值比[OR]=3.53；95%置信区间[CI]=2.46 - 5.09；以及OR = 4.73；3.26 - 6.88）。然而，血清抗幽门螺杆菌免疫球蛋白G（IgG）抗体呈阳性（OR = 1.09；0.7 – 1.61）与胃癌无关，即使按年龄大于或小于50岁进行分析也是如此。细胞色素P450 2E1（CYP2E1）RsaI多态性和谷胱甘肽 - S - 转移酶（GST）M1基因缺失的特定基因型已被确定，但与胃癌无关；然而，Lmyc基因多态性与胃癌有关（OR = 1.55；1.03 - 2.34）。因此，在这项日本研究中，血清胃蛋白酶原水平所表明的萎缩性黏膜变化可能是胃癌的一个危险因素。
