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Matrix Metalloproteinase-1 Gene Promoter Polymorphism and Risk of Ovarian Cancer

Brian Calingaert, MS

Shazia Ali

Kia McClean

Regina Whitaker

Rex Bentley, MD

Johnathan M. Lancaster, MD

Joellen Schildkraut, PhD

Jeffrey Marks, PhD

Departments of Obstetrics and Gynecology/Division of Gynecologic Oncology, Pathology, Community and Family Medicine, and Surgery, Duke University Medical Center, Durham, North Carolina

Andrew Berchuck, MD

Departments of Obstetrics and Gynecology/Division of Gynecologic Oncology, Pathology, Community and Family Medicine, and Surgery, Duke University Medical Center, Durham, North Carolina; Division of Gynecologic Oncology, Duke University Medical Center, Box 3079, Durham NC 27710; berch001{at}mc.duke.edu

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Key Words: Matrix metalloproteinase-1 • ovarian cancer • polymorphism

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 6, 381-387 (2003)
DOI: 10.1016/S1071-55760300141-2


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