Association of genetic polymorphism in the DNA repair gene XPD with risk of lung cancer in nonsmoking females / 中国肺癌杂志

ABSTRACT

<p><b>BACKGROUND</b>Xeroderma pigmentosum group D (XPD) is one of the important DNA repair genes. XPD polymorphism at Lys751Gln site has been shown to alter XPD protein function, modulate DNA repair capacity and therefore affect cancer risk. The aim of this study is to explore the relationship between XPD polymorphism and susceptibility to lung cancer in nonsmoking female via a population-based case-control study.</p><p><b>METHODS</b>There were 105 female patients who were diagnosed with lung cancer between January 2004 and December 2005 from Liaoning Tumor Hospital and 202 Hospital, and the control group included 105 healthy volunteers who were obtained from community centers at the same time. Information concerning demographic and risk factors was obtained for each case and control by a trained interviewer. XPD genotypes of cases and controls were determined by PCR-RFLP method. Two-sided Chi-Square test was used to compare the distribution of the genotypes and risk factors between cases and controls. Unconditional logistic regression analysis was performed to calculate the odds ratios (OR) with 95% confidence intervals (CI) for estimating the association between certain genotypes and lung cancer and exploring the interaction of environmental risk factors and genetic polymorphism.</p><p><b>RESULTS</b>All of the subjects in this study were nonsmoking females in Shenyang. There was no significant demographic difference (age, economic level and education) between cases and controls. There was a significant difference in the frequencies of XPD polymorphism between cancer cases and controls. The frequencies of XPD 751Gln allele were 6.2% in controls and 13.8% in cases (P < 0.05). The risk of lung cancer was higher in those with the Lys/Gln or Gln/Gln genotype than in those with the Lys/Lys genotype and adjusted OR was 2.80 (95% CI 1.21-6.48). The result showed that cooking fumes exposure was a risk factor for lung cancer (OR was 2.44). Furthermore, an interaction between environmental risk factors and the variant XPD 751Gln allele on the risk of lung cancer was observed. Individuals with both risk gen-otype and exposure to cooking fumes had a higher elevated risk of cancer than those with only one of them (adjusted OR= 6.85 ; 95% CI 1.69-27.67; P=0.007).</p><p><b>CONCLUSIONS</b>The above findings indicate that the Lys751Gln polymorphism in XPD gene is associated with the risk of lung cancer in nonsmoking females. Individuals with both XPD 751Gln allele genotype and exposure to cooking fumes have a higher elevated risk of cancer than those with only one of them in nonsmoking female population.</p>