Carcinogenesis Advance Access originally published online on September 6, 2006
Carcinogenesis 2007 28(2):427-434; doi:10.1093/carcin/bgl170
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Peroxisome profilerator-activated receptor
2 Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes
1 National Institute of Occupational Health, Copenhagen Denmark
2 Institute of Science, Systems and Models, Roskilde University Roskilde
3 Institute of Cancer Epidemiology, Danish Cancer Society Copenhagen, Denmark
4 Institute of Human Genetics, University of Aarhus Aarhus, Denmark
*To whom correspondence should be addressed. Tel: +45 3916 5227; Fax: +45 3916 5201; Email: ubv{at}ami.dk
Use of non-steroid anti-inflammatory drugs (NSAIDs) has been associated with decreased risk of breast cancer in epidemiological studies. Thus, a high-inflammatory response may be associated with increased breast cancer risk. It is thus possible that genetic variations leading to a modified inflammatory response will influence breast cancer risk. The purpose of this study was to determine if polymorphisms associated with an altered inflammatory response are associated with breast cancer risk, and to investigate the possible interaction with lifestyle factors such as alcohol use, smoking and NSAID use. We matched 361 female breast cancer cases with 361 controls, nested within the prospective ‘Diet, Cancer and Health’ study. Carriers of the variant Ala-allele of PPAR
2 Pro12Ala were at lower risk of breast cancer (IRR = 0.67, 95% CI = 0.46–0.97). This was primarily due to an interaction with alcohol consumption. Alcohol consumption was associated with a 1.21-fold increased risk of breast cancer per 10 g alcohol/day (95% CI = 1.06–1.35) among homozygous wild-type carriers, whereas alcohol was not associated with breast cancer risk among variant allele carriers (P for interaction = 0.005). Non-users of NSAID, who were carriers of the variant allele of PPAR2 Pro12Ala, were at lower risk of breast cancer (IRR = 0.44; 95% CI = 0.26–0.73) compared with non-users carrying wild-type alleles (P for interaction = 0.03). No effects were found for IL6 G-174C, IL8 T-251A and COX2 T8473C. Our results suggest that PPAR2 Pro12Ala is an important determinant in alcohol mediated breast carcinogenesis. We also observe interaction between NSAID, alcohol consumption and PPAR2 Pro12Ala genotype in relation to breast cancer risk.
Abbreviations: BMI, body mass index; COX, cyclooxygenase; HRT, hormone replacement therapy; IRR, incidence rate ratios; NSAIDs, non-steroid anti-inflammatory drugs; PPAR, peroxisome profilerator-activated receptor
Received April 18, 2006; revised August 29, 2006; accepted September 2, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in Carcinogenesis:
- Peroxisome Profilerator-Activated Receptor-gamma2 Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes
Carcinogenesis 2007 28: 2062.[Extract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  F. Ondrey Peroxisome Proliferator-Activated Receptor {gamma} Pathway Targeting in Carcinogenesis: Implications for Chemoprevention Clin. Cancer Res., January 1, 2009; 15(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Venkata, C. S. Aung, P. J. Cabot, G. R. Monteith, and S. J. Roberts-Thomson PPAR{alpha} and PPAR{beta} Are Differentially Affected by Ethanol and the Ethanol Metabolite Acetaldehyde in the MCF-7 Breast Cancer Cell Line Toxicol. Sci., March 1, 2008; 102(1): 120 - 128. [Abstract] [Full Text] [PDF]
|
|