title: Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery.
abstract: BACKGROUND
  Surgical management of colon cancer for patients with Lynch syndrome who carry a mismatch repair (MMR) gene mutation is controversial. The decision to remove more or less of the colon involves the consideration of a relatively high risk of metachronous colorectal cancer (CRC) with the impact of more extensive surgery.
  
  
  OBJECTIVE
  To estimate and compare the risks of metachronous CRC for patients with Lynch syndrome undergoing either segmental or extensive (subtotal or total) resection for first colon cancer.
  
  
  METHODS
  Risk of metachronous CRC was estimated for 382 MMR gene mutation carriers (172 MLH1, 167 MSH2, 23 MSH6 and 20 PMS2) from the Colon Cancer Family Registry, who had surgery for their first colon cancer, using retrospective cohort analysis. Age-dependent cumulative risks of metachronous CRC were calculated using the Kaplan-Meier method. Risk factors for metachronous CRC were assessed by a Cox proportional hazards regression.
  
  
  RESULTS
  None of 50 subjects who had extensive colectomy was diagnosed with metachronous CRC (incidence rate 0.0; 95% CI 0.0 to 7.2 per 1000 person-years). Of 332 subjects who had segmental resections, 74 (22%) were diagnosed with metachronous CRC (incidence rate 23.6; 95% CI 18.8 to 29.7 per 1000 person-years). For those who had segmental resections, incidence was statistically higher than for those who had extensive surgery (P <0.001). Cumulative risk of metachronous CRC was 16% (95% CI 10% to 25%) at 10 years, 41% (95% CI 30% to 52%) at 20 years and 62% (95% CI 50% to 77%) at 30 years after segmental colectomy. Risk of metachronous CRC reduced by 31% (95% CI 12% to 46%; p=0.002) for every 10 cm of bowel removed.
  
  
  CONCLUSIONS
  Patients with Lynch syndrome with first colon cancer treated with more extensive colonic resection have a lower risk of metachronous CRC than those receiving less extensive surgery. This finding will better inform decision-making about the extent of primary surgical resection.
authors.affiliation: New Zealand Familial GI Cancer Registry, Auckland City Hospital, New Zealand. sparry@adhb.govt.nz
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.forename: Bryan
authors.initials: B
authors.lastname: Parry
authors.forename: Finlay A
authors.initials: FA
authors.lastname: Macrae
authors.forename: Lyle C
authors.initials: LC
authors.lastname: Gurrin
authors.forename: James M
authors.initials: JM
authors.lastname: Church
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Leggett
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Lodge
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D017677:Age Distribution; D000368:Aged; D003082:Colectomy / Q000379:methods; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000517:prevention & control; D009687:Nuclear Proteins / Q000235:genetics; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes