Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer.
Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer.
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DOI：
10.1097/fpc.0000000000000146
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发表时间：
2015-08
影响因子：
2.6
通讯作者：
Armamento-Villareal R
中科院分区：
文献类型：
--
作者：
Napoli N;Rastelli A;Ma C;Colleluori G;Vattikuti S;Armamento-Villareal R
CYP 19 A1（芳香化酶）基因多态性影响服用芳香化酶抑制剂（AI）治疗雌激素受体阳性（ER+）乳腺癌患者的无病生存和骨丢失由于AI使用导致严重的雌激素缺乏，可能导致身体组成的变化，本研究的目的是确定CYP 19 A1基因中rs700518多态性对接受AI治疗ER+乳腺癌的绝经后女性身体组成变化的影响。这是一项为期1年的前瞻性研究，研究了开始接受第三代AI治疗ER+乳腺癌的绝经后女性的身体组成变化。在6个月和12个月时，通过双能吸收法测量身体组成，通过放射免疫法测量血清雌二醇，并通过Taqman SNP等位基因鉴别分析进行基因分型。82名妇女能够提供至少一个后续的身体成分测量。与携带A等位基因（GA/AA）的患者相比，具有rs700518 GG基因型（Val 80处的G/A）的女性在12个月时的躯干脂肪质量指数（p = 0.03）显著增加，无脂肪质量指数（p=0.01）显著降低。各基因型间雌二醇水平的变化无显著差异。具有CYP 19 A1基因rs700518多态性GG基因型的患者在AI治疗时有显著的无脂肪质量损失和躯干脂肪增加的风险。是否存在相关的代谢异常以及长期AI治疗是否会持续变化，需要在更大规模的研究中进行更长时间的随访。
Polymorphisms in the CYP19A1 (aromatase) gene influence disease-free survival and bone loss in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancers. Because AI use results in profound estrogen deficiency which may lead to changes in body composition, the objective of this study was to determine the effect of the rs700518 polymorphism in the CYP19A1 gene, on the changes in body composition among postmenopausal women who were treated with AIs for ER+ breast cancer. This is a 1-year prospective study of changes in body composition in postmenopausal women who were initiated on third-generation AIs for ER+ breast cancer. Body composition was measured by dual energy absorptiometry at 6 and 12 months, serum estradiol by radioimmunoassay and genotyping by Taqman SNP allelic discrimination assay. Eighty-two women were able to provide at least one follow-up body composition measurement. Women with the GG genotype for the rs700518 (G/A at Val80) developed a significant increase in Truncal fat mass index (p=0.03) and a significant decrease in fat-free mass index (p=0.01) at 12 months relative to patients carrying the A allele (GA/AA). There was no significant difference in the changes in estradiol levels among the genotypes. Patients with the GG genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for significant loss of fat-free mass and increase in truncal fat with AI therapy. Whether there are associated metabolic abnormalities and whether changes would persist with long-term AI therapy, need to be confirmed in a larger study with a longer duration of follow-up.