Excess of extracolonic non-endometrial multiple primary cancers in MSH2 germline mutation carriers over MLH1

J Surg Oncol. 2013 Dec;108(7):433-7. doi: 10.1002/jso.23413. Epub 2013 Oct 10.

Abstract

Background: The lynch syndrome (LS) tumor spectrum involves colorectal cancer (CRC), endometrial cancer (EC), and less frequently various extracolonic non-endometrial cancers (non-EC). The organ-specific survival rates of these patients are well defined, however, the collective survival of all-cancers combined (CRC + EC + non-EC) are unclear.

Methods: Fifty-two MSH2 patients and 68 MLH1 patients were followed for a median of 6.3 years after diagnosis of first cancer, regardless of type. The proportions of CRC only, EC, non-EC, and multiple primary cancers were compared between the two genotypes. Kaplan-Meier curves were developed for survival comparisons.

Results: MSH2 patients present less frequently with only CRC (37% MSH2, 62% MLH1, P = 0.0096), manifest more multiple primary cancers (38% MSH2, 18% MLH1, P = 0.013), develop more extracolonic cancers (62% MSH2, 38% MLH1, P = 0.003), non-EC only cancers (46% MSH2, 24% MLH1, P = 0.028) and carry a greater risk for urinary tract cancer (UTC) (13.4% MSH2, 1.5% MLH1, P = 0.024). There was no difference in 10-year survival between the two groups (P = 0.4).

Conclusion: The additional propensity for UTC in MSH2 carriers argues in favor of UTC screening in MSH2 individuals. Other types of cancer screening should be tailored to the expression history of the specific LS mutation.

Keywords: HNPCC; MLH1; MSH2; lynch syndrome; urinary tract.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Cohort Studies
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Neoplasm Staging
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Nuclear Proteins / genetics*
  • Urologic Neoplasms / genetics*
  • Urologic Neoplasms / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein