The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

Int J Cancer. 2008 Jul 15;123(2):444-449. doi: 10.1002/ijc.23508.

Abstract

Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6-10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3-9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Age Distribution
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Confounding Factors, Epidemiologic
  • DNA Mismatch Repair
  • Denmark / epidemiology
  • Female
  • Finland / epidemiology
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Mutation*
  • Neoplasms / epidemiology*
  • Neoplasms / genetics*
  • Netherlands / epidemiology
  • Nuclear Proteins / genetics*
  • Odds Ratio
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics
  • Proportional Hazards Models
  • Registries
  • United States / epidemiology
  • Urologic Neoplasms / epidemiology
  • Urologic Neoplasms / genetics

Substances

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