Associations between polymorphisms in DNA repair genes and TP53 mutations in non-small cell lung cancer.
This study was conducted to identify genetic factors predisposing to TP53 mutations in patients with non-small cell lung cancer (NSCLC). A comprehensive panel of potentially functional single nucleotide polymorphisms (SNPs) in DNA repair genes was evaluated in relation to TP53 mutations. Thirty-seven SNPs in 28 DNA repair genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. Four SNPs (XPA rs1800975, OGG1 rs1052133, ADPRT rs1136410, and NBS1 rs1805794) were significantly associated with the prevalence of TP53 mutations in multivariate analysis for each SNP. When the 4 SNPs were combined, the prevalence of TP53 mutations was increased as the number of bad genotypes increased (P(trend)=0.001). Patients with 3 and 4 bad genotypes had a significantly higher frequency of TP53 mutations than those with 0-1 bad genotypes (adjusted odds ratio=5.18, 95% confidence interval=1.51-17.81, P=0.01 and adjusted odds ratio=18.26, 95% confidence interval=2.87-116.09, P=0.002, respectively). These findings suggest that the 4 SNPs may modulate the occurrence of TP53 mutations and contribute to lung carcinogenesis. However, larger studies are required to confirm our findings in other ethnic populations.
Department of Thoracic Surgery, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu 700-412, Republic of Korea.
Sukki
S
Cho
Min Jung
MJ
Kim
Yi Young
YY
Choi
Seung Soo
SS
Yoo
Won Kee
WK
Lee
Eun Jin
EJ
Lee
Eun Jeong
EJ
Jang
Eun Young
EY
Bae
Guang
G
Jin
Hyo-Sung
HS
Jeon
Shin Yup
SY
Lee
Sung-Ick
SI
Cha
Tae In
TI
Park
Chang Ho
CH
Kim
Jae Yong
JY
Park
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53