Wenham Robert M, Calingaert Brian, Ali Shazia, McClean Kia, Whitaker Regina, Bentley Rex, Lancaster Johnathan M, Schildkraut Joellen, Marks Jeffrey, Berchuck Andrew
Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Soc Gynecol Investig. 2003 Sep;10(6):381-7. doi: 10.1016/s1071-5576(03)00141-2.
It has been suggested that the 2G allele of a guanine insertion-deletion promoter polymorphism in the promoter of the matrix metalloproteinase-1 (MMP1) gene may increase susceptibility to ovarian cancer. The 2G allele also has been associated with increased MMP1 expression. We investigated the relationship between the MMP1 polymorphism and ovarian cancer risk in a large population-based, case-control study.
The MMP1 promoter polymorphism was examined in white blood cell DNA from 311 cases and 387 age- and race-matched controls using a radiolabeled polymerase chain reaction assay. In addition, genotyping of the MMP1 polymorphism performed in 42 advanced-stage invasive serous ovarian cancers was compared to their mean relative MMP1 expression from Affymetrix microarrays.
The 2G allele frequency did not differ significantly between cases (0.49) and controls (0.48), and the distribution of genotypes was in Hardy-Weinberg equilibrium. Using 1G homozygotes as the reference group, neither 2G homozygotes (odds ratio 1.1, 95% confidence interval 0.7-1.7) nor heterozygotes plus 2G homozygotes (odds ratio 0.9, 95% confidence interval 0.7-1.3) had an increased risk of ovarian cancer. There was also no relationship between MMP1 genotype and histologic grade, histologic type, stage, or tumor behavior (borderline versus invasive). The mean MMP1 expression was twice as high in 2G homozygotes relative to 1G homozygotes, but this difference was not statistically significant.
The reported association between the MMP1 promoter polymorphism and ovarian cancer risk was not supported by our data. There was a suggestion that the 2G allele may be associated with higher MMP1 expression, and this finding is worthy of further investigation.
有人提出，基质金属蛋白酶-1（MMP1）基因启动子中鸟嘌呤插入-缺失启动子多态性的2G等位基因可能会增加患卵巢癌的易感性。2G等位基因也与MMP1表达增加有关。我们在一项基于人群的大型病例对照研究中调查了MMP1多态性与卵巢癌风险之间的关系。
使用放射性标记的聚合酶链反应分析法，对311例患者以及387例年龄和种族匹配的对照者的白细胞DNA中的MMP1启动子多态性进行检测。此外，将42例晚期侵袭性浆液性卵巢癌中MMP1多态性的基因分型结果与其在Affymetrix微阵列上的平均相对MMP1表达进行比较。
病例组（0.49）和对照组（0.48）的2G等位基因频率无显著差异，基因型分布符合哈迪-温伯格平衡。以1G纯合子作为参照组，2G纯合子（优势比1.1，95%置信区间0.7-1.7）以及杂合子加2G纯合子（优势比0.9，95%置信区间0.7-1.3）患卵巢癌的风险均未增加。MMP1基因型与组织学分级、组织学类型、分期或肿瘤行为（交界性与侵袭性）之间也无关联。2G纯合子的平均MMP1表达相对于1G纯合子高出两倍，但这种差异无统计学意义。
我们的数据不支持所报道的MMP1启动子多态性与卵巢癌风险之间的关联。有迹象表明2G等位基因可能与较高的MMP1表达有关，这一发现值得进一步研究。
