title: 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.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan. tomo@rerf.or.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Ito
authors.forename: John
authors.initials: J
authors.lastname: Cologne
authors.forename: Mayumi
authors.initials: M
authors.lastname: Maki
authors.forename: Yukari
authors.initials: Y
authors.lastname: Morishita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagamura
authors.forename: Keiko
authors.initials: K
authors.lastname: Sasaki
authors.forename: Ikue
authors.initials: I
authors.lastname: Hayashi
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.forename: Seishi
authors.initials: S
authors.lastname: Kyoizumi
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.forename: Saeko
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Masazumi
authors.initials: M
authors.lastname: Akahoshi
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D059647:Gene-Environment Interaction; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000097:blood / Q000235:genetics* / Q000473:pathology; D054043:Nuclear Weapons; D020641:Polymorphism, Single Nucleotide; D011829:Radiation Dosage; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D016753:Interleukin-10