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Carcinogenesis Advance Access published online on November 21, 2006
Carcinogenesis, doi:10.1093/carcin/bgl225
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 4, 2006
Revised November 9, 2006
Accepted November 11, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

172G>T variant in the 5' untranslated region of DNA repair gene RAD51 reduces risk of squamous cell carcinoma of the head and neck and interacts with a P53 codon 72 variant

Jiachun Lu 1, Li-E Wang 1, Ping Xiong 1, Erich M. Sturgis 2, Margaret R. Spitz 1, and Qingyi Wei 1 *

1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
2 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA

* To whom correspondence should be addressed.
Qingyi Wei, E-mail: qwei{at}mdanderson.org


  Abstract

RAD51 participates in homologous recombination (HR) repair of double-stranded DNA breaks (DSBs) that may cause genomic instability and cancer. Two single nucleotide polymorphisms (SNPs) and three P53 binding sites have been found in the RAD51 promoter and 5' untranslated region. We hypothesized that RAD51 and P53 SNPs may interact and alter risk of squamous cell carcinoma of the head and neck (SCCHN) and we genotyped for RAD51 135G>C and 172G>T and P53 Arg72Pro SNPs in 716 SCCHN patients and 719 matched controls (all non-Hispanic whites) and evaluated their effects on gamma radiation-induced mutagen sensitivity. We found that RAD51 172TT homozygotes had a significantly decreased risk (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI] = 0.50-0.87) of SCCHN, compared with carriers of other genotypes, particularly in P53 Arg72Arg homozygotes (adjusted OR = 0.60; 95% CI = 0.41-0.89) (homogeneity test P = 0.047), although no alterations in the risk were associated with the RAD51 135G>C and P53 Arg72Pro SNPs. Consistent with a protective effect of the 172 TT genotype, significantly fewer gamma radiation-induced chromatid breaks per cell were present in 172 TT homozygotes (mean ± SD = 0.36 ± 0.13) than in subjects with other genotypes (mean ± SD = 0.46 ± 0.13; P < 0.001) among 148 control subjects we tested. These finding that the functional RAD51 172G>T SNP, particularly in the presence of the P53 Arg72Arg genotype, may be a marker of susceptibility to SCCHN needs to be validated by larger studies of different ethnic populations.

Keywords: Case-control study; DNA repair; Genetic susceptibility; Molecular epidemiology; Mutagen sensitivity.
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