Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

Are there any real Helicobacter pylori infection-negative gastric cancers in Asia?

The great variability in gastric cancer rates across Asia, with very high incidences in Japan and Korea, and exceedingly low incidences in ethnic Malays, whether in Malaysia or Indonesia, appears largely due to variation in Helicobacter pylori infection rates. While between 2% and 10.6% of gastric cancers in a recent Japanese survey were considered to be negative for bacterial infection on the basis of seropositivity and H. pylori-dependent mucosal atrophy, it is notoriously difficult to preclude past infection. The situation is greatly complicated by reported differences in the etiology of gastric cardia and non-cardia cancers. In the Western world there do appear to be tumours arising close to the esophageal-gastric junction which are not related to H. pylori and associated inflammation, but in most Asian populations these appear to be very rare. Therefore preventive efforts, and particularly screening, should be focused on markers of bacterial infection, with avoidance of unnecessary exposure to X-ray radiation.