Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

Acta Obstet Gynecol Scand. 2008;87(11):1129-35. doi: 10.1080/00016340802443806.


Objective: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) families. Data in the Danish HNPCC register on the frequency and lifetime risk of gynecologic cancers were analyzed and the actual surveillance strategy discussed in relation to the results.

Design: Register-based retrospective study.

Method: A total of 1,780 at-risk women were identified and epidemiological, clinical and MMR gene mutation data were retrieved.

Results: In a total of 105 cases of endometrial cancer, there was no significant difference in MSH2, MSH6 and MLH1 mutation carrier frequency. Compared to the general population, mutation carriers had a 20 times increase in lifetime risk of endometrial cancer. Lifetime risk was elevated four times in familial CRC families. In these families, frequency was correlated to the pedigree phenotype, with significantly higher frequency demonstrated in Amsterdam II families compared to Amsterdam I families and families suspected of HNPCC. A total of 39 cases of ovarian cancer were identified with a lifetime risk of three to four times the general population. No significant correlation was found between the frequency of ovarian cancer and MMR gene mutation status in the families.

Conclusion: The benefit of surveillance concerning gynecological cancers seems to be less well founded in familial CRC families than in Lynch syndrome families. Modifying the surveillance strategy may be relevant in the future, but before changing existing guidelines concerning surveillance, further research is recommended.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair
  • DNA-Binding Proteins / genetics
  • Denmark / epidemiology
  • Endometrial Neoplasms / epidemiology*
  • Endometrial Neoplasms / genetics
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Lynch Syndrome II / epidemiology
  • Lynch Syndrome II / genetics
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • Nuclear Proteins / genetics
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / genetics
  • Population Surveillance
  • Registries
  • Retrospective Studies
  • Risk Assessment*
  • Risk Factors


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein