和基因多态性在泌乳素瘤中的作用：基因多态性可能与肿瘤缩小有关。

The Role of and Gene Polymorphisms in Prolactinoma: Gene Polymorphisms May Be Associated with Tumor Shrinkage.

作者信息

Turgut Seda, Ilhan Muzaffer, Turan Saime, Karaman Ozcan, Yaylim Ilhan, Kucukhuseyin Ozlem, Tasan Ertugrul

机构信息

Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey.

Department of Endocrinology and Metabolism, Bezmialem Vakif University, Istanbul, Turkey.

出版信息

In Vivo. 2017 May-Jun;31(3):357-363. doi: 10.21873/invivo.11067.

DOI:10.21873/invivo.11067

PMID:28438863

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5461445/

Abstract

AIM

Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and mouse double minute 2 (MDM2) (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma.

PATIENTS AND METHODS

A total of 74 patients with prolactinoma and 100 age- and gender-matched healthy individuals were enrolled in the study. Serum prolactin levels were measured by enzyme-linked immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis.

RESULTS

p16 540C→G genotype distribution was found to be: CC: 66.2%, CG: 28.4%, GG: 5.4%; p16 580C→T genotype distribution was found to be: CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT: 31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (r=0.719, p<0.001, p=0.034 r=0.256, respectively). The number of patients with tumor size decrease of more than 50% in those with homozygous genotype (TT+GG) of MDM2 SNP309T→G was significantly higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95% confidence interval(CI)=0.06-0.58; p=0.003).

CONCLUSION

This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.

摘要

目的

催乳素瘤被认为起源于单个突变细胞的克隆性扩增，该细胞受到多种许可因子的生长刺激，尽管肿瘤发生的发病机制仍不清楚。本研究旨在探讨p16（540C→G和580C→T）和小鼠双微体2（MDM2）（SNP309T→G）基因多态性在催乳素瘤肿瘤发生及特征中的作用。

患者与方法

本研究共纳入74例催乳素瘤患者和100名年龄及性别匹配的健康个体。采用酶联免疫吸附测定（ELISA）法测定血清催乳素水平。通过聚合酶链反应-限制性片段长度多态性和琼脂糖凝胶电泳确定p16和MDM2基因多态性。

结果

催乳素瘤患者中，p16 540C→G基因型分布为：CC：66.2%，CG：28.4%，GG：5.4%；p16 580C→T基因型分布为：CC：82.4%，CT：17.6%，TT：0%；MDM2基因型分布为：TT：31.1%，TG：47.3%，GG：21.6%。治疗前肿瘤直径与治疗前催乳素水平及治疗后催乳素降低百分比相关（r分别为0.719，p<0.001；p=0.034，r=0.256）。MDM2 SNP309T→G纯合基因型（TT+GG）患者肿瘤大小缩小超过50%的人数显著高于杂合基因型（TG）携带者（优势比（OR）=0.18，95%置信区间（CI）=0.06-0.58；p=0.003）。