title: Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands.
abstract: OBJECTIVE
  Although gastric cancer forms part of the Lynch syndrome tumor spectrum, the risk of developing gastric cancer in Lynch syndrome families is unknown, resulting in a lack of clear guidelines for surveillance. The aim of this study was to evaluate incidence trends and risk of developing gastric cancer among Lynch syndrome mutation carriers in a Western population.
  
  
  METHODS
  Lynch syndrome mutation carriers were selected from the Dutch Hereditary Cancer Registry. The gastric cancer incidence in Lynch syndrome mutation carriers was compared to the gastric cancer incidence in the Dutch population between 1970 and 2003. Standardized incidence ratios were calculated by a Poisson model. Cumulative risks were calculated by Kaplan-Meier analysis.
  
  
  RESULTS
  Overall, 2014 Lynch syndrome mutation carriers were identified. Gastric cancer was diagnosed in 32 (1.6%) subjects (male/female: 21/11), 22 (69%) of them had a negative family history of gastric cancer. The standardized incidence ratios of gastric cancer was 3.4 (95% confidence interval, 2.1-5.2) and showed a nonsignificant decline between 1970 and 2003 (P = .30). Absolute risk of developing gastric cancer also showed no significant change over time (P = .51). Lifetime risk of developing gastric cancer was 8.0% in males vs 5.3% in females (P = .02), and 4.8% and 9% for MLH1 and MSH2 carriers, respectively. None of the 378 MSH6 carriers developed gastric cancer (P = .002 vs MLH1 and MSH2 combined lifetime risk).
  
  
  CONCLUSIONS
  Lynch syndrome mutation carriers have a substantial risk for gastric cancer, in particular patients with an MLH1 or MSH2 mutation. Family history for gastric cancer is a poor indicator for individual risk. Surveillance gastroscopy for Lynch syndrome patients carrying an MLH1 or MSH2 mutation should therefore be considered.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. L.Capelle@erasmusmc.nl
authors.forename: Lisette G
authors.initials: LG
authors.lastname: Capelle
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: Van Grieken
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Klokman
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Bruno
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics; D011159:Population Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein