Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Metabolism. 2011 Sep;60(9):1234-43. doi: 10.1016/j.metabol.2011.01.005. Epub 2011 Mar 12.
Studies have linked prostate cancer risk with insulin resistance and obesity. Circulating levels of adiponectin, a protein involved in insulin resistance and obesity, have been associated with prostate cancer risk. We studied the association of prostate cancer risk with haplotype tagging single nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) chosen based on their functional relevance or association with other types of cancer. DNA samples from 465 cases and 441 healthy volunteers from New York City were genotyped for ADIPOQ rs266729, rs822395, rs822396, rs1501299, and rs2241766 SNPs and ADIPOR1 rs12733285, rs1342387, rs7539542, rs2232853, and rs10920531 SNPs. We performed both single- and multiple-SNP analyses. We found that rs12733285, rs7539452, rs266729, rs822395, rs822396, and rs1501299 were significantly associated with prostate cancer risk. Haplotype analysis confirmed these results and identified 5 ADIPOQ 4-SNP haplotypes and 1 ADIPOR1 2-SNP haplotype tightly associated with prostate cancer risk. Importantly, 2 ADIPOQ SNPs, rs266729 and rs1501299, have been previously associated with colon and breast cancer risk, respectively, in the same direction as in this study. These findings suggest that variants of the adiponectin pathway may be associated with susceptibility to various forms of common cancers and warrant validation studies.
研究表明,前列腺癌风险与胰岛素抵抗和肥胖有关。循环脂肪细胞素(一种与胰岛素抵抗和肥胖有关的蛋白质)水平与前列腺癌风险相关。我们研究了基于其功能相关性或与其他类型癌症的关联而选择的脂肪细胞素(ADIPOQ)和脂肪细胞素受体 1(ADIPOR1)单核苷酸多态性(SNP)的单体型标记与前列腺癌风险的关联。来自纽约市的 465 例病例和 441 例健康志愿者的 DNA 样本用于 ADIPOQ rs266729、rs822395、rs822396、rs1501299 和 rs2241766 SNPs 以及 ADIPOR1 rs12733285、rs1342387、rs7539542、rs2232853 和 rs10920531 SNPs 的基因分型。我们进行了单 SNP 和多 SNP 分析。我们发现 rs12733285、rs7539452、rs266729、rs822395、rs822396 和 rs1501299 与前列腺癌风险显著相关。单体型分析证实了这些结果,并确定了 5 个 ADIPOQ 4-SNP 单体型和 1 个 ADIPOR1 2-SNP 单体型与前列腺癌风险密切相关。重要的是,2 个 ADIPOQ SNPs,rs266729 和 rs1501299,分别与本研究中相同方向的结肠癌和乳腺癌风险相关。这些发现表明,脂肪细胞素通路的变异可能与各种常见癌症的易感性有关,需要进一步的验证研究。