Epidemiology, Preventive Medicine, Harvard School of Public Health, 677 Huntington Avenue · Boston, MA 02115.Channing Lab, Brigham & Women's Hospital and Harvard Medical School.
Adiponectin, an insulin-sensitizing adipokine, is inversely associated with adiposity and prostate cancer risk and progression. However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown.
In a nested case-control study of 1286 cases and 1267 controls within the Physicians' Health Study, we evaluated 28 common single nucleotide polymorphisms (SNPs) in ADIPOQ (13), ADIPOR1(5) and ADIPOR2(11) in relation to the risk of prostate cancer. In subgroups, we also evaluated the association of genotype and circulating adiponectin levels (n=951) and prostate tumor expression of insulin receptor (IR) and insulin-like growth factor 1 (IGF-1R) receptor (n=181).
Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052, rs822391, rs2082940) were significantly associated (p< 0.05) with overall prostate cancer risk, with no significant difference by tumor grade or clinical stage. Two of the risk SNPs (rs266729, rs182052) plus four other SNPs (rs16861209, rs17366568, rs3774261, rs7639352) were also associated with plasma adiponectin levels and three of these (rs1686109, rs17366568, rs3774261) were also significantly associated with IR expression in prostate tumor tissue. One additional SNP was associated with IGF1-R tumor tissue expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to cancer risk or circulating adiponectin levels.
Common variants in the adiponectin gene were associated with prostate cancer risk, plasma adiponectin levels, and IR or IGF-1R expression in the prostate tumor. Impact: These genotype-phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development.
Dhillon PK, Penney KL, Schumacher F, Rider JR, Sesso HD, Pollack M, Fiorentino M, Finn S, Loda M, Rifai N, Mucci LA, Giovannucci EL, Stampfer MJ, Ma J. Are you the author?
Reference: Cancer Epidemiol Biomarkers Prev. 2011 Sep 29. Epub ahead of print.