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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.

Publication ,  Journal Article
Lu, J; Wang, L-E; Xiong, P; Sturgis, EM; Spitz, MR; Wei, Q
Published in: Carcinogenesis
May 2007

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 172TT genotype, significantly fewer gamma radiation-induced chromatid breaks per cell were present in 172TT 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. The 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.

Duke Scholars

Published In

Carcinogenesis

DOI

ISSN

0143-3334

Publication Date

May 2007

Volume

28

Issue

5

Start / End Page

988 / 994

Location

England

Related Subject Headings

  • Thymidine
  • Radiation Effects
  • Rad51 Recombinase
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms
 

Citation

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Lu, J., Wang, L.-E., Xiong, P., Sturgis, E. M., Spitz, M. R., & Wei, Q. (2007). 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. Carcinogenesis, 28(5), 988–994. https://doi.org/10.1093/carcin/bgl225
Lu, Jiachun, Li-E Wang, Ping Xiong, Erich M. Sturgis, Margaret R. Spitz, and Qingyi Wei. “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.Carcinogenesis 28, no. 5 (May 2007): 988–94. https://doi.org/10.1093/carcin/bgl225.
Lu, Jiachun, et al. “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.Carcinogenesis, vol. 28, no. 5, May 2007, pp. 988–94. Pubmed, doi:10.1093/carcin/bgl225.
Journal cover image

Published In

Carcinogenesis

DOI

ISSN

0143-3334

Publication Date

May 2007

Volume

28

Issue

5

Start / End Page

988 / 994

Location

England

Related Subject Headings

  • Thymidine
  • Radiation Effects
  • Rad51 Recombinase
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms