title: Interaction of polymorphisms in the interleukin 1B-31 and general transcription factor 2A1 genes on the susceptibility to gastric cancer.
abstract: Proinflammatory genotypes of the IL-1 (interleukin-1) gene have been associated with an increased gastric cancer risk in Caucasians, whereas some studies in Asian populations did not find such association. Furthermore, the risk genotypes differed somewhat between Caucasian and Asian populations. These findings might reflect more complex genetic mechanisms in Asian compared with Caucasian populations. Therefore, we examined a polymorphism (rs1864169) in the general transcription factor 2A1 (GTF2A1) gene as a test of the hypothesis that this transcription factor and IL-IB gene polymorphisms interact in the effects on the gastric cancer risk due to the possible biological relationship between the two genes. Genotyping of the 515 control and 342 case samples was performed by primer extension assay and SNaPshot assays. We found an association between carriage of the IL1B-31C allele and gastric cancer among Koreans, which was observed only in subjects with GTF2A1 GG genotype. The GTF2A1GG/IL1B-31C carrier genotype combination showed stronger association with diffuse type gastric cancer cases. These findings indicate that the effect of the two genetic polymorphisms on risk of gastric cancer is synergistic. Our results also suggest that an additional host genetic factor acting epistatically may differentially contribute to the histogenesis of the diffuse and intestinal subtypes.
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Sohn
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Rhee
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics*; D035165:Transcription Factors, General / Q000235:genetics*
chemical_list: D053583:Interleukin-1beta; D035165:Transcription Factors, General