Relative frequency and morphology of cancers in STK11 mutation carriers

Gastroenterology. 2004 Jun;126(7):1788-94. doi: 10.1053/j.gastro.2004.03.014.

Abstract

Background & aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS).

Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11.

Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank chi(2) = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank chi(2) = 1.31; P = 0.25) or between familial and sporadic cases (log-rank chi(2) = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin--gastroesophageal, small bowel, colorectal, and pancreatic--and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years.

Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics*
  • Female
  • Gastrointestinal Neoplasms / epidemiology*
  • Gastrointestinal Neoplasms / genetics*
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mutation, Missense
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / genetics
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk Factors

Substances

  • STK11 protein, human
  • Protein-Serine-Threonine Kinases