Identification of polymorphisms in the XIAP gene and analysis of association with lung cancer risk in a Korean population.
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.
Kang
Hyo-Gyoung
HG
Cancer Research Institute, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, 700-422, Republic of Korea.
Lee
Su Jeong
SJ
Chae
Myung Hwa
MH
Lee
Won Kee
WK
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Kam
Sin
S
Park
Rang-Woon
RW
Kim
In-San
IS
Kim
Dong Sun
DS
Kim
Young Chul
YC
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
D051636:X-Linked Inhibitor of Apoptosis Protein