Polymorphisms in estrogen biosynthesis and metabolism-related genes, ionizing radiation exposure, and risk of breast cancer among US radiologic technologists.
Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1,083 controls within the US radiologic technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR = 0.3; 95% CI 0.1-0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR = 1.2; 95% CI 0.9-1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic X-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (p (interaction) = 0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic X-ray exposure (p (interaction) = 0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.
Sigurdson
Alice J
AJ
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, EPS 7060, MSC 7238, Bethesda, MD, 20892-7238, USA. sigurdsa@mail.nih.gov
Bhatti
Parveen
P
Chang
Shih-Chen
SC
Rajaraman
Preetha
P
Doody
Michele M
MM
Bowen
Laura
L
Simon
Steven L
SL
Weinstock
Robert M
RM
Linet
Martha S
MS
Rosenstein
Marvin
M
Stovall
Marilyn
M
Alexander
Bruce H
BH
Preston
Dale L
DL
Struewing
Jeffery P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008660:Metabolism / Q000235:genetics*; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D009784:Occupational Diseases / Q000209:etiology / Q000235:genetics*; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011839:Radiation, Ionizing; D011859:Radiography / Q000009:adverse effects*; D011874:Radiometry; D012306:Risk; D013679:Technology, Radiologic; D014481:United States / Q000453:epidemiology
D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1