Effects Of Il10 Haplotypes And Atomic Bomb Radiation Exposure On Risks Of Gastric Cancer Subtypes

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Gastric cancer is one of the cancers whose risks of incidence and mortality clearly increased among Japanese atomic-bomb (A-bomb) survivors. Gastric cancer incidence in the Radiation Effects Research Foundation's (RERF) Life Span Study cohort population increased with radiation dose and remains high even today, more than 65 years since exposure. In this study, we specifically examined the association between risk of gastric cancer (intestinal and diffuse types) and radiation exposure by haplotypes of the immunosuppressive gene IL10 to investigate inter-individual differences in gastric cancer susceptibility associated with radiation exposure. Methods: We analyzed the follow-up data from the RERF Immunogenome Study Cohort of 4,690 A-bomb survivors at baseline covering 1981-2005: a total of 200 gastric cancer cases comprising 93 intestinal-type, 96 diffuse-type, and 11 other subtypes. Relative risk (RR) for IL10 and excess relative risk (ERR) for radiation of gastric cancer subtypes were estimated. Using a single haplotype block composed of four haplotype-tagging single nucleotide polymorphisms (comprising major haplotype allele IL10-ATTA and minor haplotype allele IL10-GGCG), multiplicative and additive models for joint effects of radiation and this IL10 haplotyping were examined. Results: The RR of intestinal-type gastric cancer among A-bomb survivors harboring the minor homozygote was significantly high, being 2.2 (95% confidence interval (CI): 1.1-4.3), compared to those harboring the major homozygote. In other words, the IL10 minor haplotype allele was considered to be a risk factor for intestinal-type gastric cancer. However, no significant association was observed between radiation exposure and intestinal-type gastric cancer, and no statistical interaction was observed between radiation exposure and IL10 haplotypes. The IL10 minor haplotype allele was not a risk factor for diffuse-type gastric cancer. The ERR per Gy of radiation exposure by haplotype showed statistical significance only for the major homozygote (0.46/Gy, 95% CI: 0.02-1.4). On the other hand, the ERR per Gy for the minor homozygote was close to 0, with no statistical significance. Therefore, the IL10 minor haplotype allele might act to suppress the radiation-associated risk elevation of diffuse-type gastric cancer. Conclusion: This study of A-bomb survivors suggests that IL10 haplotypes may be associated with the development of radiation-related diffuse-type gastric cancer. There is a possibility, therefore, that immune/inflammatory-related gene polymorphisms may be involved in inter-individual differences in radiation-related cancer risks. Further studies based on genome-wide association analysis are currently underway. Citation Format: Tomonori Hayashi, John B. Cologne, Yiqun Hu, Kengo Yoshida, Waka Ohishi, Ikue Hayashi, Junko Kajimura, Seishi Kyoizumi, Yoichiro Kusunoki, Kei Nakachi. Effects of IL10 haplotypes and atomic bomb radiation exposure on risks of gastric cancer subtypes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2209. doi:10.1158/1538-7445.AM2014-2209