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The MYH gene encodes a DNA glycosylase involved in the excision repair of adenines paired with 8-hydroxyguanines, a major component of oxidative DNA damage, and bi-allelic germline MYH mutations have been reported to predispose individuals to multiple colorectal adenomas and carcinoma. To determine whether the MYH gene is involved in gastric carcinogenesis, we examined blood specimens from 20 Japanese familial gastric cancer (GC) patients for MYH mutations by polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP) analysis followed by direct sequencing. Bi-allelic germline MYH mutations were not found in any of the specimens, but in addition to four known variants, a novel splice-site variant, IVS10-2A > G (c.892-2A > G), was found in two patients as its heterozygote. Reverse transcription–PCR analysis revealed that the IVS10-2A > G variant caused the production of an aberrant mRNA transcript encoding a truncated MYH protein. Immunofluorescence analysis showed that the wild-type MYH protein, but not the variant-type, is localized in the nucleus. We then searched for the IVS10-2A > G variant in 128 digestive tract cancer patients by PCR with confronting two-pair primers, and eight cancers from six patients with the IVS10-2A/G genotype were identified. However, no other germline MYH mutations or inactivation of the remaining wild-type allele was detected. We next tested the presumed correlation of the IVS10-2G allele with GC risk in a case-control study of 148 GC cases and 292 controls, but no significant difference in the distribution of the IVS10-2A > G variant was found between the cases and controls. Interestingly, the homozygote for the IVS10-2G allele was found in one GC case, but not in any controls. These results suggested that the ability to repair 8-hydroxyguanine in nuclear DNA may differ among Japanese individuals due to the splicing abnormality based on the MYH IVS10-2A > G variant, and that the bi-allelic IVS10-2A > G variation may be responsible for the occurrence of GC. [ABSTRACT FROM AUTHOR]

Background Although Helicobacter pylori infection is a major risk factor for gastric cancer, it does not explain the full picture of stomach carcinogenesis. There have been few epidemiological studies, however, which examined both H. pylori and environmental factors simultaneously. The aims of this study were to estimate the association of environmental factors (smoking and dietary factors) with gastric cancer in consideration of H. pylori infection, and to investigate the effects of the interaction between environmental factors and H. pylori infection. Methods A multicenter, hospital-based, case-control study of gastric cancer was conducted at four hospitals in Nagano prefecture, Japan, between October 1998 and March 2002. For 153 newly diagnosed gastric cancer cases, two controls matched by age (within 3 years), sex, and residence area were randomly selected from the participants of a health check-up program during the same period in the same hospitals. We conducted a questionnaire survey and obtained blood samples. Consequently, 122 non-cardia gastric cancer cases and 235 controls were available for this analysis. Results Results. H. pylori infection was strongly associated with non-cardia gastric cancer after adjustment for possible confounding factors (odds ratio [OR], 8.2; 95% confidence interval [CI], 3.7?18.2). Cigarette smoking (OR, 2.8; 95% CI, 1.2?6.5) and frequent intake of miso (fermented soy bean) soup (OR, 2.1; 95% CI, 0.9?5.1) and rice (OR, 2.5; 95% CI, 1.0?6.1) were determined to be risk factors even after adjusting for possible confounding factors, including H. pylori infection. However, no statistically significant interaction between environmental factors and H. pylori infection was detected. Conclusion This finding suggests that although H. pylori infection is clearly an important risk factor for gastric cancer, smoking cessation and dietary modification may be practical strategies for the prevention of non-cardia gastric cancer among both H. pylori-positive and -negative subjects in Japan. [ABSTRACT FROM AUTHOR]