Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China.
The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs.
Shen
Min
M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7240, USA. shenmi@mail.nih.gov
Berndt
Sonja I
SI
Rothman
Nathaniel
N
Demarini
David M
DM
Mumford
Judy L
JL
He
Xingzhou
X
Bonner
Matthew R
MR
Tian
Linwei
L
Yeager
Meredith
M
Welch
Robert
R
Chanock
Stephen
S
Zheng
Tongzhang
T
Caporaso
Neil
N
Lan
Qing
Q
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014157:Transcription Factors / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5
D004265:DNA Helicases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C513287:RAD23B protein, human; C095888:xeroderma pigmentosum group F protein; C086985:RAD23A protein, human; C086984:XPC protein, human; C071447:ERCC1 protein, human; C497292:ERCC2 protein, human