Abstract
An epidemiologic study was conducted to determine whether polymorphisms in DNA repair genes modify the association between breast cancer risk and exposure to ionizing radiation. Self-reported exposure to ionizing radiation from medical sources was evaluated as part of a population-based, case-control study of breast cancer in African-American (894 cases and 788 controls) and White (1,417 cases and 1,234 controls) women. Genotyping was conducted for polymorphisms in four genes involved in repair of radiation-induced DNA damage, the double-strand break repair pathway: X-ray cross-complementing group 3 (XRCC3) codon 241 Thr/Met, Nijmegen breakage syndrome 1 (NBS1) codon 185 Glu/Gln, X-ray cross-complementing group 2 (XRCC2) codon 188 Arg/His, and breast cancer susceptibility gene 2 (BRCH2) codon 372 Asn/His. Allele and genotype frequencies were not significantly different in cases compared with controls for all four genetic polymorphisms, and odds ratios for breast cancer were close to the null. Combining women with two, three, and four variant genotypes, a positive association was observed between breast cancer and number of lifetime mammograms (P(trend) < 0.0001). No association was observed among women with zero or one variant genotype (P = 0.86). Odds ratios for radiation treatments to the chest and number of lifetime chest X-rays were slightly elevated but not statistically significant among women with two to four variant genotypes. The study has several limitations, including inability to distinguish between diagnostic and screening mammograms or reliably classify prediagnostic mammograms and chest X-rays in cases. Prospective studies are needed to address whether common polymorphisms in DNA repair genes modify the effects of low-dose radiation exposure from medical sources.
Highlights
Exposure to ionizing radiation is a well-established risk factor for breast cancer [1,2,3]
single-nucleotide polymorphisms (SNP) were chosen according to the following criteria: (a) essential role for the gene in HRR, (b) minimum frequency for the less common allele of z5% in African Americans or Whites, (c) previous laboratory data and/or computer simulations suggesting significant functional effect, (d) previous epidemiologic studies showing an association with breast cancer or susceptibility to ionizing radiation, and (e) calculations that showed we had sufficient power to stratify on combinations of four genetic polymorphisms when estimating Odds ratios (ORs) for number of lifetime mammograms
We studied the effects of exposure to ionizing radiation from medical procedures in a population-based, case-control study of breast cancer in African-American and White women in North Carolina
Summary
Exposure to ionizing radiation is a well-established risk factor for breast cancer [1,2,3]. Epidemiologic studies consistently show elevated breast cancer risk following moderate to highdose radiation exposure. Risk of breast cancer from exposure to very low levels of ionizing radiation, such as chest X-rays and mammograms, is controversial [1]. Based on linear extrapolation from high to low dose, some researchers estimate the carcinogenic effects of very low level radiation exposure to be negligible [4]. Assessing cancer risk from low-dose radiation presents several obstacles, including the difficulties in measuring lifetime exposure, the large sample sizes needed to quantify effects, and the appropriateness of linear extrapolation from high to low dose [1, 4]
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