Identification of polymorphisms in the XIAP gene and analysis of association with lung cancer risk in a Korean population

Hyo Gyoung Kang, Su Jeong Lee, Myung Hwa Chae, Won Kee Lee, Sung Ick Cha, Chang Ho Kim, Sin Kam, Rang Woon Park, In San Kim, Dong Sun Kim, Young Chul Kim, Tae Hoon Jung, Jae Yong Park

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Abstract

The X-linked inhibitor of apoptosis protein (XIAP) is a potent mammalian IAP, and has been shown to play an important role in development and progression of cancer. Polymorphisms in the XIAP gene may influence XIAP production or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we first screened for polymorphisms in the XIAP gene by direct sequencing of genomic DNA samples from 27 healthy Korean women and then performed a case-control study to evaluate the association between the polymorphisms and the risk of lung cancer. The XIAP genotypes were determined by polymerase chain reaction amplification and melting curve analysis in 582 lung cancer patients and in 582 healthy control subjects who were frequency-matched for age and sex. We identified 12 single nucleotide polymorphisms (SNPs), one novel SNP [30051C>G (A321G) in exon 3] and the following 11 known SNPs: 192G>C (rs5956578), 262C>T (rs28382699), 318C>T (rs5958318), and 374C>T (rs12687176) in the putative promoter; 26615A>G (rs2355676) in intron 1; 41725A>G (rs5958338) in intron 5; 42009A>C (Q423P, rs5956583) in exon 6; 48162T>C (rs17334739) and 48228C>T (rs28382739) in intron 6; and 48542A>G (rs28382740) and 49333G>T (rs28382742) in 3′-UTR. Four of these 12 SNPs were selected for large-scale genotyping based on their frequencies and haplotype tagging status: 262C>T, 318C>T, 374C>T, and 42009A>C. The four XIAP polymorphisms and their haplotypes exhibited no apparent relationship with the risk of lung cancer. In addition, we observed no evidence of effect modification by age, sex, smoking history, or tumor histology. These results suggest that XIAP polymorphisms do not significantly affect susceptibility to lung cancer in Koreans.

Original languageEnglish
Pages (from-to)6-13
Number of pages8
JournalCancer Genetics and Cytogenetics
Volume180
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kang, H. G., Lee, S. J., Chae, M. H., Lee, W. K., Cha, S. I., Kim, C. H., Kam, S., Park, R. W., Kim, I. S., Kim, D. S., Kim, Y. C., Jung, T. H., & Park, J. Y. (2008). Identification of polymorphisms in the XIAP gene and analysis of association with lung cancer risk in a Korean population. Cancer Genetics and Cytogenetics, 180(1), 6-13. https://doi.org/10.1016/j.cancergencyto.2007.07.021