ABSTRACT
It is widely reported that reactive oxygen species (ROS) cause apotosis and carcinogenesis. Marked infiltration of activated leukocyte and enhanced production of ROS appear to occur in the gastric mucosa infected with Helicobacter pylori (H. pylori). The previous studies reported that the mutation of the succinate dehydrogenase subunit C (SDHC) gene caused the increase in superoxide anion (O(2)(-)) and oxidative stress. To extend these findings, we epidemiologically investigated the association of a SDHC polymorphism at 3'-untranslated region of exon 6 (JST173800) with H. pylori infection, gastric atrophy and gastric cancer risk in Japan. The subjects consisted of 454 health checkup examinees without a history of cancer and 202 gastric cancer patients. The SDHC polymorphism was not associated with H. pylori infection seropositivity, gastric atrophy, and cancer risk in this study. Although the polymorphism at the 3'-untranslated region could be hypothesized to be functional, this study did not demonstrate any significant association of the SDHC gene polymorphism with gastric atrophy and cancer.
Subject(s)
Adult , Aged , Aged, 80 and over , Atrophy , Case-Control Studies , Chi-Square Distribution , Exons , Female , Genotype , Helicobacter Infections/complications , Helicobacter pylori/pathogenicity , Humans , Japan/epidemiology , Logistic Models , Male , Middle Aged , Oxidative Stress , Pepsinogens/blood , Polymorphism, Genetic , Risk Factors , Stomach Neoplasms/enzymology , Succinate Dehydrogenase/geneticsABSTRACT
Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.