Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database

Gut. 2017 Sep;66(9):1657-1664. doi: 10.1136/gutjnl-2016-311403. Epub 2016 Jun 3.

Abstract

Objective: Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?

Design: Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.

Results: 1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%).

Conclusions: Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94-1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer.

Keywords: CANCER GENETICS; COLORECTAL CANCER GENES; EPIDEMIOLOGY; INHERITED CANCERS; SCREENING.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
  • DNA Mismatch Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Europe / epidemiology
  • Female
  • Genetic Variation
  • Germ-Line Mutation
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • MutL Protein Homolog 1 / genetics*
  • MutS Homolog 2 Protein / genetics*
  • Neoplasm Staging
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Survival Analysis

Substances

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