Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men

Abstract

Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48–0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10−3). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.

Association Between the Body Mass Index and Prostate Cancer at Biopsy is Modified by Genetic Risk

“…For example, Gu et al reported a different association of ADIPOQ genetic variants, which is an important molecular mechanism responsible for the link between obesity and PCa, and with PCa risks in the normal weight and overweight subgroups. 19 Lifestyle intervention can reduce the risk of diabetes progression by ≥50% in high-risk individuals. 20 In our results, the identified interaction between BMI and GRS suggests that environmental factors associated with obesity may modify inherited risk factors.…”

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy

“… 37 38 Furthermore, altered levels of circulating adipokines are also associated with PCa risk and PCa invasion. 39 40 Thus, further studies are warranted to reveal the complex molecular mechanisms by which MetS is linked to PCa.…”

A single nucleotide polymorphism inADIPOQpredicts biochemical recurrence after radical prostatectomy in localized prostate cancer

“…We selected to genotype rs266729 (5′ flanking region), rs182052 (intron 1) to tag block 1 and rs3774262 (intron 2) to tag block 2. These PCa risk-associated SNPs were reported to be significantly associated with serum adiponectin simultaneously [ 9 , 10 ]. Genotyping was done after extraction of DNA from whole blood using a standard QIAmp kit (QIAGEN Inc.) protocol using TaqMan real-time PCR method as described previously [ 10 ].…”

“…These PCa risk-associated SNPs were reported to be significantly associated with serum adiponectin simultaneously [ 9 , 10 ]. Genotyping was done after extraction of DNA from whole blood using a standard QIAmp kit (QIAGEN Inc.) protocol using TaqMan real-time PCR method as described previously [ 10 ]. All SNPs had greater than 99% completion and the concordance was 100% for duplicated specimens.…”

“…To our knowledge, three ADIPOQ single nucleotide polymorphisms (SNPs) (rs182052, rs266729 and rs3774262) were shown to be associated with both PCa susceptibility and adiponectin levels [ 9 , 10 ]. They have been found to either have potentially functionality [ 11 ] or are associated with PCa clinicopathologic characteristics [ 10 ]. It is conceivable that these SNPs might influence PCa clinical outcome through modulation of adiponectin levels, which promotes a favorable microenvironment for PCa progression.…”