Journal
CANCER CAUSES & CONTROL
Volume 25, Issue 11, Pages 1513-1521Publisher
SPRINGER
DOI: 10.1007/s10552-014-0454-7
Keywords
Heterocyclic amines; Aromatic amines; PhIP; 4-Aminobiphenyl; Smoking
Funding
- Prevent Cancer Foundation
- National Institutes of Health [R01 GM61753]
- NIH/NIEHS training grant in Molecular and Environmental Toxicology [T32 ES007015]
- Specialized Program of Research Excellence (SPORE) in Breast Cancer at UNC [NIH/NCI P50-CA58223]
- Lineberger Comprehensive Cancer Center Core Grant [P30-CA16086]
- NIH/NIGMS grant [U19 GM061388]
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Cytochrome b (5) (encoded by CYB5A) and NADH cytochrome b (5) reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women. We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking. A CYB5R3 variant, I1M+6T (rs8190370), was significantly more common in breast cancer cases (MAF 0.0238) compared with controls (0.0169, p = 0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared with AfrAm controls (0.0441, p = 0.046; adjusted OR 1.41, CI 0.98-2.04; p = 0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08-4.07; p = 0.028) compared with never smokers (OR = 1.21; 0.77-1.88; p for interaction = 0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared with Caucs. CYB5R3 I1M+6C > T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers.
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