title: Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists.
abstract: High-dose ionizing radiation exposure to the breast and rare autosomal dominant genes have been linked with increased breast cancer risk, but the role of low-to-moderate doses from protracted radiation exposure in breast cancer risk and its potential modification by polymorphisms in DNA repair genes has not been previously investigated among large numbers of radiation-exposed women with detailed exposure data. Using carefully reconstructed estimates of cumulative breast doses from occupational and personal diagnostic ionizing radiation, we investigated the potential modification of radiation-related breast cancer risk by 55 candidate single nucleotide polymorphisms in 17 genes involved in base excision or DNA double-strand break repair among 859 cases and 1083 controls from the United States Radiologic Technologists (USRT) cohort. In multivariable analyses, WRN V114I (rs2230009) significantly modified the association between cumulative occupational breast dose and risk of breast cancer (adjusted for personal diagnostic exposure) (p = 0.04) and BRCA1 D652N (rs4986850), PRKDC IVS15 + 6C > T (rs1231202), PRKDC IVS34 + 39T > C (rs8178097) and PRKDC IVS31 - 634C > A (rs10109984) significantly altered the personal diagnostic radiation exposure-response relationship (adjusted for occupational dose) (p < or = 0.05). None of the remaining 50 SNPs significantly modified breast cancer radiation dose-response relationships. The USRT genetic study provided a unique opportunity to examine the joint effects of common genetic variation and ionizing radiation exposure on breast cancer risk using detailed occupational and personal diagnostic exposure data. The suggestive evidence found for modification of radiation-related breast cancer risk for 5 of the 55 SNPs evaluated requires confirmation in larger studies of women with quantified radiation breast doses in the low-to-moderate range.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892-7238, USA. bhattip@mail.nih.gov
authors.forename: Parveen
authors.initials: P
authors.lastname: Bhatti
authors.forename: Jeffery P
authors.initials: JP
authors.lastname: Struewing
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Alexander
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: Laura
authors.initials: L
authors.lastname: Bowen
authors.forename: Lutecia H
authors.initials: LH
authors.lastname: Mateus-Pereira
authors.forename: Marbin A
authors.initials: MA
authors.lastname: Pineda
authors.forename: Steven L
authors.initials: SL
authors.lastname: Simon
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weinstock
authors.forename: Marvin
authors.initials: M
authors.lastname: Rosenstein
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Dale L
authors.initials: DL
authors.lastname: Preston
authors.forename: Martha S
authors.initials: MS
authors.lastname: Linet
authors.forename: Michele M
authors.initials: MM
authors.lastname: Doody
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000209:etiology; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011839:Radiation, Ionizing; D012189:Retrospective Studies; D012307:Risk Factors; D013679:Technology, Radiologic; D014481:United States / Q000453:epidemiology; D000078329:Workforce
chemical_list: D045643:DNA Repair Enzymes