Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists.
OBJECTIVE
Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk.


METHODS
We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose-response across genotypes.


RESULTS
There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2-12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0-3.8) and EOR/Gy < 0 (95%CI < 0-14.8) for the GC and CC genotypes, respectively, (p (interaction) = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined.


CONCLUSIONS
This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.
Schonfeld
Sara J
SJ
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, 6120 Executive Blvd MSC 7238, Bethesda, MD 20892, USA. schonfes@mail.nih.gov
Bhatti
Parveen
P
Brown
Elizabeth E
EE
Linet
Martha S
MS
Simon
Steven L
SL
Weinstock
Robert M
RM
Hutchinson
Amy A
AA
Stovall
Marilyn
M
Preston
Dale L
DL
Alexander
Bruce H
BH
Doody
Michele M
MM
Sigurdson
Alice J
AJ
D000488:Allied Health Personnel; D001943:Breast Neoplasms / Q000150:complications / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics; D009784:Occupational Diseases / Q000209:etiology* / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011839:Radiation, Ionizing; D012306:Risk; D013679:Technology, Radiologic
D051546:Cyclooxygenase 2