Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk

Virginia G. Kaklamani, Maureen Sadim, Alex Hsi, Kenneth Offit, Carole Oddoux, Harry Ostrer, Habibul Ahsan, Boris Pasche, Christos Mantzoros

Research output: Contribution to journalArticle

74 Citations (Scopus)

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; Ptrend = 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.

Original languageEnglish (US)
Pages (from-to)3178-3184
Number of pages7
JournalCancer Research
Volume68
Issue number9
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Adiponectin Receptors
Adiponectin
Breast Neoplasms
Genes
Confidence Intervals
Odds Ratio
Single Nucleotide Polymorphism
Haplotypes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kaklamani, V. G., Sadim, M., Hsi, A., Offit, K., Oddoux, C., Ostrer, H., ... Mantzoros, C. (2008). Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. Cancer Research, 68(9), 3178-3184. https://doi.org/10.1158/0008-5472.CAN-08-0533

Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. / Kaklamani, Virginia G.; Sadim, Maureen; Hsi, Alex; Offit, Kenneth; Oddoux, Carole; Ostrer, Harry; Ahsan, Habibul; Pasche, Boris; Mantzoros, Christos.

In: Cancer Research, Vol. 68, No. 9, 01.05.2008, p. 3178-3184.

Research output: Contribution to journalArticle

Kaklamani, VG, Sadim, M, Hsi, A, Offit, K, Oddoux, C, Ostrer, H, Ahsan, H, Pasche, B & Mantzoros, C 2008, 'Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk', Cancer Research, vol. 68, no. 9, pp. 3178-3184. https://doi.org/10.1158/0008-5472.CAN-08-0533
Kaklamani, Virginia G. ; Sadim, Maureen ; Hsi, Alex ; Offit, Kenneth ; Oddoux, Carole ; Ostrer, Harry ; Ahsan, Habibul ; Pasche, Boris ; Mantzoros, Christos. / Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. In: Cancer Research. 2008 ; Vol. 68, No. 9. pp. 3178-3184.
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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; Ptrend = 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.",
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