Effects of IL-10 haplotype and atomic bomb radiation exposure on gastric cancer risk.

Abstract

Gastric cancer (GC) is one of the cancers that reveal increased risk of mortality and incidence in atomic bomb survivors. The incidence of gastric cancer in the Life Span Study cohort of the Radiation Effects Research Foundation (RERF) increased with radiation dose (gender-averaged excess relative risk per Gy = 0.28) and remains high more than 65 years after exposure. To assess a possible role of gene-environment interaction, we examined the dose response for gastric cancer incidence based on immunosuppression-related IL-10 genotype, in a cohort study with 200 cancer cases (93 intestinal, 96 diffuse and 11 other types) among 4,690 atomic bomb survivors participating in an immunological substudy. Using a single haplotype block composed of four haplotype-tagging SNPs (comprising the major haplotype allele IL-10-ATTA and the minor haplotype allele IL-10-GGCG, which are categorized by IL-10 polymorphisms at -819A>G and -592T>G, +1177T>C and +1589A>G), multiplicative and additive models for joint effects of radiation and this IL-10 haplotyping were examined. The IL-10 minor haplotype allele(s) was a risk factor for intestinal type gastric cancer but not for diffuse type gastric cancer. Radiation was not associated with intestinal type gastric cancer. In diffuse type gastric cancer, the haplotype-specific excess relative risk (ERR) for radiation was statistically significant only in the major homozygote category of IL-10 (ERR = 0.46/Gy, P = 0.037), whereas estimated ERR for radiation with the minor IL-10 homozygotes was close to 0 and nonsignificant. Thus, the minor IL-10 haplotype might act to reduce the radiation related risk of diffuse-type gastric cancer. The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer.

• Authors: Tomonori Hayashi, Reiko Ito, John Cologne, Mayumi Maki, Yukari Morishita, Hiroko Nagamura, Keiko Sasaki, Ikue Hayashi, Kazue Imai, Kengo Yoshida, Junko Kajimura, Seishi Kyoizumi, Yoichiro Kusunoki, Waka Ohishi, Saeko Fujiwara, Masazumi Akahoshi, Kei Nakachi
• Journal: Radiation research (Radiat Res) Vol. 180 Issue 1 Pg. 60-9 (Jul 2013) ISSN: 1938-5404 [Electronic] United States
• PMID: 23772925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2013 by Radiation Research Society

Chemical References

• Interleukin-10

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Gene-Environment Interaction
• Haplotypes
• Humans
• Interleukin-10 (blood, genetics)
• Male
• Middle Aged
• Neoplasms, Radiation-Induced (blood, genetics, pathology)
• Nuclear Weapons
• Polymorphism, Single Nucleotide
• Radiation Dosage
• Risk Factors
• Stomach Neoplasms (blood, genetics, pathology)