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A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking.

Publication ,  Journal Article
Hu, Z; Ma, H; Lu, D; Zhou, J; Chen, Y; Xu, L; Zhu, J; Huo, X; Qian, J; Wei, Q; Shen, H
Published in: Pharmacogenet Genomics
July 2005

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base-excision repair pathway. Functional Polymorphisms in the XRCC1 gene may lead to decreased DNA repair capacity and thus confer inherited predisposition to cancer risk. In this case-control study of 710 patients with incident lung cancer and 710 cancer-free controls who were frequency matched on age, sex and residential area, we genotyped a novel T>C transition at the promoter region (-77T>C) of XRCC1 and other two common non-synonymous polymorphisms (Arg194Trp and Arg399Gln) to determine their associations with risk of lung cancer. We found that compared with the -77TT wild-type homozygote, the variant genotypes were associated with significantly increased risk of lung cancer [adjusted odds ratio (OR)=1.51; 95% confidence interval (CI)=1.17-1.94 for -77TC; OR=2.98; 95% CI=0.93-9.59 for -77CC; and OR=1.55; 95% CI=1.21-1.98 for -77TC/CC]. By contrast, no significant associations were observed between the other two exonic variants (Arg194Trp and Arg399Gln) and lung cancer risk. Furthermore, we observed a 9.82-fold increased risk (95% CI=5.66-17.02) for heavy smokers carrying the -77C variant (-77TC/CC) and a 4.07-fold increased risk (95% CI=2.85-5.81) for heavy smokers not carrying the variant. However, the interaction between the -77T>C variant and cumulative smoking was not statistically significant (P=0.1560). These findings indicate that the new XRCC1 -77T>C polymorphism may contribute to the aetiology of lung cancer. Further functional studies are warranted to elucidate the underlying molecular mechanisms of the association.

Duke Scholars

Published In

Pharmacogenet Genomics

DOI

ISSN

1744-6872

Publication Date

July 2005

Volume

15

Issue

7

Start / End Page

457 / 463

Location

United States

Related Subject Headings

  • X-ray Repair Cross Complementing Protein 1
  • Smoking
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Hu, Z., Ma, H., Lu, D., Zhou, J., Chen, Y., Xu, L., … Shen, H. (2005). A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics, 15(7), 457–463. https://doi.org/10.1097/01.fpc.0000167329.85163.0d
Hu, Zhibin, Hongxia Ma, Daru Lu, Jiannong Zhou, Yijiang Chen, Lin Xu, Jingfu Zhu, et al. “A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking.Pharmacogenet Genomics 15, no. 7 (July 2005): 457–63. https://doi.org/10.1097/01.fpc.0000167329.85163.0d.
Hu Z, Ma H, Lu D, Zhou J, Chen Y, Xu L, et al. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics. 2005 Jul;15(7):457–63.
Hu, Zhibin, et al. “A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking.Pharmacogenet Genomics, vol. 15, no. 7, July 2005, pp. 457–63. Pubmed, doi:10.1097/01.fpc.0000167329.85163.0d.
Hu Z, Ma H, Lu D, Zhou J, Chen Y, Xu L, Zhu J, Huo X, Qian J, Wei Q, Shen H. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics. 2005 Jul;15(7):457–463.

Published In

Pharmacogenet Genomics

DOI

ISSN

1744-6872

Publication Date

July 2005

Volume

15

Issue

7

Start / End Page

457 / 463

Location

United States

Related Subject Headings

  • X-ray Repair Cross Complementing Protein 1
  • Smoking
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male