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Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer.

Publication ,  Journal Article
Wenham, RM; Calingaert, B; Ali, S; McClean, K; Whitaker, R; Bentley, R; Lancaster, JM; Schildkraut, J; Marks, J; Berchuck, A
Published in: J Soc Gynecol Investig
September 2003

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.

Duke Scholars

Published In

J Soc Gynecol Investig

DOI

ISSN

1071-5576

Publication Date

September 2003

Volume

10

Issue

6

Start / End Page

381 / 387

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Odds Ratio
  • Obstetrics & Reproductive Medicine
  • Neoplasm Invasiveness
  • Middle Aged
 

Citation

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Wenham, R. M., Calingaert, B., Ali, S., McClean, K., Whitaker, R., Bentley, R., … Berchuck, A. (2003). Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer. J Soc Gynecol Investig, 10(6), 381–387. https://doi.org/10.1016/s1071-5576(03)00141-2
Wenham, Robert M., Brian Calingaert, Shazia Ali, Kia McClean, Regina Whitaker, Rex Bentley, Johnathan M. Lancaster, Joellen Schildkraut, Jeffrey Marks, and Andrew Berchuck. “Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer.J Soc Gynecol Investig 10, no. 6 (September 2003): 381–87. https://doi.org/10.1016/s1071-5576(03)00141-2.
Wenham RM, Calingaert B, Ali S, McClean K, Whitaker R, Bentley R, et al. Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer. J Soc Gynecol Investig. 2003 Sep;10(6):381–7.
Wenham, Robert M., et al. “Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer.J Soc Gynecol Investig, vol. 10, no. 6, Sept. 2003, pp. 381–87. Pubmed, doi:10.1016/s1071-5576(03)00141-2.
Wenham RM, Calingaert B, Ali S, McClean K, Whitaker R, Bentley R, Lancaster JM, Schildkraut J, Marks J, Berchuck A. Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer. J Soc Gynecol Investig. 2003 Sep;10(6):381–387.
Journal cover image

Published In

J Soc Gynecol Investig

DOI

ISSN

1071-5576

Publication Date

September 2003

Volume

10

Issue

6

Start / End Page

381 / 387

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Odds Ratio
  • Obstetrics & Reproductive Medicine
  • Neoplasm Invasiveness
  • Middle Aged