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A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China
  1. Somdat Mahabir1,
  2. Christian C Abnet2,
  3. You-Lin Qiao3,
  4. Luke D Ratnasinghe4,
  5. Sanford M Dawsey2,
  6. Zhi-Wei Dong3,
  7. Philip R Taylor5,
  8. Steven D Mark6
  1. 1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  3. 3Department of Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
  4. 4Center for Structural Genomics, NCTR, Food and Drug Administration, Jefferson and Arkansas Cancer Research Center, UAMS, Little Rock, Arkansas, USA
  5. 5Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  6. 6Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  1. Correspondence to:
 Dr S Mahabir
 Department of Epidemiology, CPB4.3247, UT MD Anderson Cancer Center, Unit 1340, 1155 Pressler Blvd, Houston, TX 77030, USA;smahabir{at}mdanderson.org

Abstract

Background: Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations.

Aim: To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref-1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China.

Methods: The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real-time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age- and a sex-stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs.

Results: No association was observed between polymorphisms in APE/ref-1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010).

Conclusions: Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke.

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Footnotes

  • Competing interests: None declared.

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