Influence of polymorphisms of loci encoding DNA repair proteins on cancer susceptibility and G2 chromosomal radiosensitivity

Craig S. Wilding, Gillian B. Curwen, E. Janet Tawn, Xiaohua Sheng, Jeanette F. Winther, Ranajit Chakraborty, John D. Boice

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Sixteen condidate polymorphisms (13 SNPs ond 3 microsotellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G2 chromosomal radiosensitivity. Genotype at the Asp 148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G2 radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G 2 radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity.

Original languageEnglish
Pages (from-to)48-57
Number of pages10
JournalEnvironmental and Molecular Mutagenesis
Volume48
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Cancer susceptibility
  • Chromosomal radiosensitivity
  • DNA repair genes

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