Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: The Western New York Exposures and Breast Cancer (WEB) Study

Theodore M. Brasky, Matthew R. Bonner, Kirsten B. Moysich, Heather M. Ochs-Balcom, Catalin Marian, Christine B. Ambrosone, Jing Nie, Menghua Tao, Stephen B. Edge, Maurizio Trevisan, Peter G. Shields, Jo L. Freudenheim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)157-165
Number of pages9
JournalBreast Cancer Research and Treatment
Volume126
Issue number1
DOIs
StatePublished - 1 Feb 2011

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Inflammatory Breast Neoplasms
Cyclooxygenase 2
Anti-Inflammatory Agents
Breast Neoplasms
Pharmaceutical Preparations
Breast
Aspirin
Single Nucleotide Polymorphism
Carcinogenesis
Odds Ratio
Confidence Intervals
Inflammation
Ibuprofen
Motor Vehicles
Medicare
Case-Control Studies
Logistic Models
Population

Keywords

  • Breast cancer
  • Cyclooxygenase-2
  • Non-steroidal anti-inflammatory drugs
  • Prostaglandinendoperoxide synthase 2
  • Single nucleotide polymorphism

Cite this

Brasky, Theodore M. ; Bonner, Matthew R. ; Moysich, Kirsten B. ; Ochs-Balcom, Heather M. ; Marian, Catalin ; Ambrosone, Christine B. ; Nie, Jing ; Tao, Menghua ; Edge, Stephen B. ; Trevisan, Maurizio ; Shields, Peter G. ; Freudenheim, Jo L. / Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk : The Western New York Exposures and Breast Cancer (WEB) Study. In: Breast Cancer Research and Treatment. 2011 ; Vol. 126, No. 1. pp. 157-165.
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abstract = "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.",
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Brasky, TM, Bonner, MR, Moysich, KB, Ochs-Balcom, HM, Marian, C, Ambrosone, CB, Nie, J, Tao, M, Edge, SB, Trevisan, M, Shields, PG & Freudenheim, JL 2011, 'Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: The Western New York Exposures and Breast Cancer (WEB) Study', Breast Cancer Research and Treatment, vol. 126, no. 1, pp. 157-165. https://doi.org/10.1007/s10549-010-1082-x

Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk : The Western New York Exposures and Breast Cancer (WEB) Study. / Brasky, Theodore M.; Bonner, Matthew R.; Moysich, Kirsten B.; Ochs-Balcom, Heather M.; Marian, Catalin; Ambrosone, Christine B.; Nie, Jing; Tao, Menghua; Edge, Stephen B.; Trevisan, Maurizio; Shields, Peter G.; Freudenheim, Jo L.

In: Breast Cancer Research and Treatment, Vol. 126, No. 1, 01.02.2011, p. 157-165.

Research output: Contribution to journalArticle

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T1 - Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk

T2 - The Western New York Exposures and Breast Cancer (WEB) Study

AU - Brasky, Theodore M.

AU - Bonner, Matthew R.

AU - Moysich, Kirsten B.

AU - Ochs-Balcom, Heather M.

AU - Marian, Catalin

AU - Ambrosone, Christine B.

AU - Nie, Jing

AU - Tao, Menghua

AU - Edge, Stephen B.

AU - Trevisan, Maurizio

AU - Shields, Peter G.

AU - Freudenheim, Jo L.

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