Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer.
Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer.
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DOI：
10.1158/1055-9965.epi-11-0434
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Ma J
中科院分区：
文献类型：
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作者：
Dhillon PK;Penney KL;Schumacher F;Rider JR;Sesso HD;Pollak M;Fiorentino M;Finn S;Loda M;Rifai N;Mucci LA;Giovannucci E;Stampfer MJ;Ma J
脂联素是一种胰岛素增敏脂肪因子，与肥胖和前列腺癌风险及进展呈负相关。然而，脂联素（ADIPOQ）和受体基因（ADIPOR 1/R2）的遗传变异在前列腺癌中的作用在很大程度上是未知的。在医生健康研究中对1286例病例和1267名对照进行的巢式病例对照研究中，我们评估了ADIPOQ（n=13）、ADIPOR 1（n=5）和ADIPOR 2（n= 5）中29种常见单核苷酸多态性（SNP）与前列腺癌风险的关系。11。在亚组中，我们还评估了基因型和循环脂联素水平（n=951）与前列腺肿瘤胰岛素受体（IR）和胰岛素样生长因子1（IGF-1 R）受体表达（n=181）的相关性。在ADIPOQ的12个标签多态性中，4个（rs 266729、rs 182052、rs 822391、rs 2082940）与总体前列腺癌风险显著相关（p<0.05），肿瘤分级或临床分期无显著差异。两个风险SNP（rs 266729，rs 182052）加上其他四个SNP（rs 16861209，rs 17366568，rs3774261，rs7639352）也与血浆脂联素水平相关，其中三个（rs 1686109、rs 17366568、rs3774261）也与前列腺肿瘤组织中的IR表达显著相关。另一个SNP与IGF 1-R肿瘤组织表达相关（rs 16861205）。ADIPOR 1/R2的16个变异体中没有一个与癌症风险或循环脂联素水平相关。脂联素基因的常见变异与前列腺癌风险、血浆脂联素水平和前列腺肿瘤中IR或IGF-1 R表达相关。这些基因型-表型相关性支持脂联素与前列腺癌发生的生物学相关性，特别是在发展的早期阶段。
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 29 common single nucleotide polymorphisms (SNPs) in ADIPOQ (n=13), ADIPOR1(n=5) and ADIPOR2(n=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. These genotype-phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development.