Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer.
DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents, such as those found in tobacco smoke. Reduced DNA repair capacity, therefore, can increase the susceptibility to smoking-related cancers. Recently, three coding polymorphisms in X-ray cross-complementing group 1 (XRCC1) DNA repair gene have been identified, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility. We investigated the relationship between the codon 399 polymorphism in XRCC1 gene and lung cancer risk in male smokers. The study population consisted of 192 lung cancer patients and 135 healthy controls. The distribution of XRCC1 genotypes was not significantly different between cases and controls. When the cases were categorized by histological type, however, the presence of at least one Gln allele was associated with a significant increased risk for squamous cell carcinoma [crude odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.06-2.93 and adjusted OR = 1.66, 95% CI = 0.99-2.79]. The risk for the disease increased as the number of Gln alleles increased (Arg/Gln genotype: adjusted OR = 1.45, 95% CI = 0.84-2.5; Gln/Gln genotype: adjusted OR = 3.26, 95% CI = 1.17-9.15). When the subjects dichotomized by cigarette consumption into two pack-year groups (< or =40 pack-years, >40 pack-years), the Gln allele was associated with an increased risk for squamous cell carcinoma only in the group of individuals having < or =40 pack-years of smoking (Arg/Gln genotype: adjusted OR = 1.48, 95% CI = 0.78-2.8; Gln/Gln genotype: adjusted OR = 5.75, 95% CI = 1.46-22.69). These results suggest that XRCC1 codon 399 polymorphism may be an important genetic determinant of squamous cell carcinoma of the lung in persons with lower degrees of cigarette use.
Park
Jae Yong
JY
Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Taegu, 700-412 Korea. jaeyong@kyungpook.ac.kr
Lee
Su Yeon
SY
Jeon
Hyo-Sung
HS
Bae
Nack Chun
NC
Chae
Sang Chul
SC
Joo
Soyoung
S
Kim
Chang Ho
CH
Park
Jae-Ho
JH
Kam
Sin
S
Kim
In San
IS
Jung
Tae Hoon
TH
D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D018287:Carcinoma, Large Cell / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human