title: Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II Nutrition Cohort.
abstract: Paraoxonase 1 (PON1) plays an important role in the high-density lipoprotein-mediated prevention of low-density lipoprotein oxidation and the metabolism of lipid-soluble radicals. In this study, we investigated the association of two common, nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M) with breast cancer risk in postmenopausal women through a nested case-control study within the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Using conditional logistic regression of genotyping results from 502 cases and 502 cancer-free controls matched on age, race/ethnicity, and date of blood draw, we found that the L55M single nucleotide polymorphism (SNP) was associated with an increased risk of breast cancer [odds ratio (OR), 1.58; 95% confidence interval (95% CI), 1.05-2.37 for MM]. No association was found for the Q192R SNP. The L55M association with breast cancer was modified by nonsteroidal anti-inflammatory drug (NSAID) use. The association was limited to women who took NSAIDs and was somewhat stronger among women who reported regular (> or = 15 times per month) NSAID use (OR, 3.24; 95% CI, 1.17-9.00) than in those who reported any NSAID use (OR, 2.46; 95% CI, 1.39-4.36). These results suggest that genetic variation in PON1, particularly at the L55M SNP, may be associated with increased risk of breast cancer in postmenopausal women. Furthermore, NSAID use seems to modify this risk.
authors.affiliation: Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Road, Northeast, Atlanta, GA 30329, USA. Victoria.Stevens@cancer.org
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Alexandre L
authors.initials: AL
authors.lastname: Pavluck
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D043303:Aryldialkylphosphatase