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Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery
  1. Susan Parry1,2,*,
  2. Aung Ko Win3,*,
  3. Bryan Parry4,
  4. Finlay A Macrae5,
  5. Lyle C Gurrin3,
  6. James M Church6,
  7. John A Baron7,
  8. Graham G Giles8,
  9. Barbara A Leggett9,10,
  10. Ingrid Winship11,
  11. Lara Lipton12,
  12. Graeme P Young13,
  13. Joanne P Young10,14,
  14. Caroline J Lodge3,
  15. Melissa C Southey15,
  16. Polly A Newcomb16,
  17. Loïc Le Marchand17,
  18. Robert W Haile18,
  19. Noralane M Lindor19,
  20. Steven Gallinger20,21,
  21. John L Hopper3,
  22. Mark A Jenkins3
  1. 1New Zealand Familial GI Cancer Registry, Auckland City Hospital, New Zealand
  2. 2Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
  3. 3Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia
  4. 4Colorectal Surgical Unit, Auckland City Hospital, New Zealand
  5. 5Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Victoria, Australia
  6. 6Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
  7. 7Department of Medicine and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA
  8. 8Cancer Epidemiology Centre, Cancer Council Victoria, Australia
  9. 9Department of Gastroenterology and Hepatology, Royal Brisbane Hospital, Brisbane, Queensland, Australia
  10. 10School of Medicine, University of Queensland, Herston, Queensland, Australia
  11. 11Adult Clinical Genetics, The University of Melbourne, Victoria, Australia
  12. 12Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  13. 13Flinders Centre for Cancer Prevention and Control, Flinders University, South Australia, Australia
  14. 14Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia
  15. 15Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
  16. 16Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  17. 17Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, USA
  18. 18Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
  19. 19Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA
  20. 20Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  21. 21Cancer Care Ontario, Toronto, Ontario, Canada
  1. Correspondence to Dr Susan Parry, NZ Familial GI Cancer Registry, Building 30, Auckland City Hospital, Private Bag 92024, Auckland, New Zealand; sparry{at}


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.

Design 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.

  • Lynch syndrome
  • metachronous colorectal cancer
  • colorectal surgery
  • family cancer

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  • Disclaimer: The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Cancer Family Registries, nor does mention of trade names, commercial products, or organisations imply endorsement by the US government or the Cancer Family Registry. Authors had full responsibility for the design of the study, the collection of the data, the analysis and interpretation of the data, the decision to submit the manuscript for publication and the writing of the manuscript.

  • * SP, AKW are joint first authors.

  • Funding This work was supported by the National Cancer Institute, National Institutes of Health under Request for Application #CA-95-011 and through cooperative agreements with the Australasian Colorectal Cancer Family Registry (UO1 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (UO1 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (UO1 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (UO1 CA074783), Seattle Colorectal Cancer Family Registry (UO1 CA074794) and The University of Hawaii Colorectal Cancer Family Registry (UO1 CA074806).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the institutional review board at each Colon Cancer Family Registry recruitment site.

  • Provenance and peer review Not commissioned; externally peer reviewed.