XRCC1 polymorphisms: Effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency

Ruth M. Lunn, Ronald G. Langlois, Ling Ling Hsieh, Claudia L. Thompson, Douglas A. Bell*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

553 Scopus citations

Abstract

Hereditary genetic defects in DNA repair lead to increased risk of cancer. Polymorphisms in several DNA repair genes have been identified; however, the impact on repair phenotype has not been elucidated. We explored the relationship between polymorphisms in the DNA repair enzyme, XRCC1 (codons 194, 280, and 399), and genotoxic end points measured in two populations: (a) placental aflatoxin B1 DNA (AFB1-DNA) adducts in a group of Taiwanese maternity subjects (n = 120); and (b) somatic glycophorin A (GPA) variants in erythrocytes from a group of North Carolina smokers and nonsmokers (n = 59). AFB1-DNA adducts were measured by ELISA, and erythrocyte GPA variant frequency (NN and NO) was assessed in MN heterozygotes with a flow cytometric assay. XRCC1 genotypes were identified by PCR-RFLPs. The XRCC1 399Gln allele was significantly associated with higher levels of both AFB1-DNA adducts and GPA NN mutations. Individuals with the 399Gln allele were at risk for detectable adducts (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.03). GPA NN variant frequency was significantly higher in 399Gln homozygotes (19.6 x 10-6) than in Gln/Arg heterozygotes (11.4 x 10-6; P < 0.05) or Arg/Arg homozygotes (10.1 x 10- 6; P = 0.01). No significant effects were observed for other XRCC1 polymorphisms. These results suggest that the Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in deficient DNA repair.

Original languageEnglish
Pages (from-to)2557-2561
Number of pages5
JournalCancer Research
Volume59
Issue number11
StatePublished - 01 06 1999
Externally publishedYes

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