Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study.
Chronic inflammation has been consistently associated with cancers of several sites, including the breast, and inhibition of inflammation through the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with risk. As NSAIDs bind with cyclooxygenase-2 (COX-2), genetic variation in COX-2 may influence breast cancer risk by affecting inflammatory response and response to NSAID use. We identified eight single nucleotide polymorphisms (SNPs) for COX-2 and examined their association with risk of breast cancer in a population-based case-control study in Western New York. Cases had incident, first primary, histologically confirmed breast cancer (n = 1077). Controls (n = 1910) were randomly selected from NY Department of Motor Vehicles records (< 65) or Medicare rolls (≥ 65). Participants were queried on adult lifetime use of aspirin and recent use of ibuprofen. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). One SNP, rs2745559, was associated with an increased risk of breast cancer (OR 1.23, 95% CI 1.03-1.46). Associations with other variants were not evident. Significant interaction (P interaction = 0.04) between recent aspirin use and rs4648261 was also observed. Variation in COX-2 was modestly associated with breast cancer risk, indicating that COX-2 may play a role in breast carcinogenesis. Better understanding of the role of COX-2 genetic variation and interaction with NSAID use in breast carcinogenesis has potential to inform prevention strategies.
Brasky
Theodore M
TM
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA. tbrasky@fhcrc.org
Bonner
Matthew R
MR
Moysich
Kirsten B
KB
Ochs-Balcom
Heather M
HM
Marian
Catalin
C
Ambrosone
Christine B
CB
Nie
Jing
J
Tao
Meng Hua
MH
Edge
Stephen B
SB
Trevisan
Maurizio
M
Shields
Peter G
PG
Freudenheim
Jo L
JL
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D017322:Clinical Trials, Phase II as Topic; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin; D007052:Ibuprofen