Authors' Affiliations: Department of Chronic Disease Epidemiology, Yale School of Public Health; Department of Surgery, Yale School of Medicine, New Haven, Connecticut; Department of Epidemiology, Shanghai Cancer Institute, Jiao Tong University; Department of Pancreas and Hepatobiliary Surgery, Shanghai Medical College, Fudan University, Shanghai, China; and Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):172-8. doi: 10.1158/1055-9965.EPI-13-0447. Epub 2013 Nov 14.
Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain-specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common.
We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays.
Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index.
Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma.
H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site.
幽门螺杆菌定植引起的胃内酸度变化可能会通过 CagA 阴性菌菌株类型、胃酸过多和增加胰腺癌风险，或 CagA 阳性菌菌株、胃酸过少和降低胰腺癌风险，来调节胰腺致癌物质的作用。我们旨在确定在 CagA 阳性菌株定植较为常见的人群中，幽门螺杆菌菌株与胰腺癌之间的特定关联。
我们在中国上海进行了一项大型胰腺癌病例对照研究。从 761 名病例患者和 794 名按年龄和性别类别匹配的随机选择的对照者中抽取静脉血标本。采用商业酶联免疫吸附 IgG 测定法检测 H. pylori 及其毒力蛋白 CagA 的抗体血清阳性率。
与既无 H. pylori 又无 CagA 抗体血清阳性的个体相比，CagA 抗体血清阳性与胰腺癌风险降低相关（调整后的 OR，0.68；95%置信区间[CI]，0.54-0.84），而 CagA 阴性 H. pylori 抗体血清阳性则提示风险略有增加（OR，1.28；95%CI，0.76-2.13）。在 CagA 血清阳性与性别、吸烟或年龄 21 岁时的体重指数之间未观察到风险交互作用。
与动物模型中的观察结果相似，我们的结果为人类提供了提示性证据，表明通过 H. pylori CagA 菌株类型的定植，胃酸的双向变化可能参与了胰腺癌的发病风险。
幽门螺杆菌定植可能对癌症风险产生多种影响，这取决于生物体菌株类型以及特定的癌症部位。
