Journal article
Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study
Human mutation, Vol.33(1), pp.158-164
01/2012
DOI: 10.1002/humu.21604
PMCID: PMC3240722
PMID: 21898661
Abstract
Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a population-based study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiation-induced breast cancer.
Details
- Title: Subtitle
- Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study
- Creators
- Jennifer D Brooks - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. brooksj@mskcc.orgSharon N TeraokaAnne S ReinerJaya M SatagopanLeslie BernsteinDuncan C ThomasMarinela CapanuMarilyn StovallSusan A SmithShan Wei - Virginia Mason InstituteRoy E ShoreJohn D Boice JrCharles F LynchLene MellemkjaerKathleen E MaloneXiaolin LiangRobert W HailePatrick ConcannonJonine L BernsteinWecare Study Collaborative Group
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.33(1), pp.158-164
- DOI
- 10.1002/humu.21604
- PMID
- 21898661
- PMCID
- PMC3240722
- NLM abbreviation
- Hum Mutat
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Publisher
- United States
- Grant note
- R01 CA129639 / NCI NIH HHS U01 CA083178-01 / NCI NIH HHS U01 CA083178 / NCI NIH HHS R01 CA137420-01A1 / NCI NIH HHS P30 CA015704 / NCI NIH HHS R01 CA114236-01 / NCI NIH HHS R01CA097397 / NCI NIH HHS R01CA114236 / NCI NIH HHS R01 CA114236 / NCI NIH HHS R01 CA137420 / NCI NIH HHS R01 AG014358 / NIA NIH HHS R01CA137420 / NCI NIH HHS R01 CA097397 / NCI NIH HHS R01 CA097397-05 / NCI NIH HHS U01CA083178 / NCI NIH HHS
- Language
- English
- Date published
- 01/2012
- Academic Unit
- Epidemiology
- Record Identifier
- 9983995018502771
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