title: Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk.
abstract: Breast cancer risk is higher among obese women and women with diabetes. Adiponectin is a protein exclusively secreted by adipose tissue, circulating levels of which have been associated with breast cancer risk. Whether genetic variants within the adiponectin pathway are associated with breast cancer risk is unknown. To explore the association of genetic variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with breast cancer risk, we conducted a case control study of female patients with breast cancer and healthy female controls from New York City recruited between 1999 and 2004. We genotyped 733 hospital-based breast cancer cases and 839 controls for 10 haplotype-tagging single nucleotide polymorphisms (SNP) of ADIPOQ and ADIPOR1. Two ADIPOQ SNPs (rs2241766 and rs1501299), which have been associated with circulating levels of adiponectin, were associated with breast cancer risk [rs1501299*GG: odd ratios (OR), 1.80; 95% confidence interval (95% CI), 1.14-2.85; rs2241766*TG: OR, 0.61; 95% CI, 0.46-0.80]. One ADIPOR1 SNP (rs7539542), which modulates expression of adiponectin receptor 1 mRNA, was also associated with breast cancer risk (OR, 0.51; 95% CI, 0.28-0.92). Based on the known function of rs2241766 and rs1501299, we categorized individuals by adiponectin signaling status and found that, when compared with high signalers, intermediate signalers had a 4.16-fold increase in breast cancer risk (95% CI, 0.49-35.19), and low signalers had a 6.56-fold increase in breast cancer risk (95% CI, 0.78-54.89; P(trend) = 0.001). This is the first report of an association between functionally relevant variants of the adiponectin pathway and breast cancer risk. The results warrant further studies of the adiponectin pathway in breast cancer.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Kaklamani
authors.forename: Maureen
authors.initials: M
authors.lastname: Sadim
authors.forename: Alex
authors.initials: A
authors.lastname: Hsi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Carole
authors.initials: C
authors.lastname: Oddoux
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.forename: Boris
authors.initials: B
authors.lastname: Pasche
authors.forename: Christos
authors.initials: C
authors.lastname: Mantzoros
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin