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Risk of Metachronous Colon Cancer Following Surgery for Rectal Cancer in Mismatch Repair Gene Mutation Carriers

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer.

Methods

This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan–Meier method.

Results

During median 9 years (range 1–32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81–37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9–31 %) at 10 years, 47 (95 % CI 31–68 %) at 20 years, and 69 % (95 % CI 45–89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01–1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III.

Conclusions

Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.

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Acknowledgment

The authors thank all study participants of the Colon Cancer Family Registry and staff for their contributions to this project.

Disclosure

The authors have no conflict of interest to declare with respect to this manuscript.

Funding

This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centers include Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). AKW is supported by the Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia. MAJ is a Senior Research Fellow and JLH is an Australia Fellow of the National Health and Medical Research Council, Australia.

Author information

Authors and Affiliations

  1. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia

    Aung Ko Win MBBS, MPH, John L. Hopper PhD & Mark A. Jenkins PhD

  2. New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand

    Susan Parry MB ChB, FRACP & Julie Arnold RN

  3. Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand

    Susan Parry MB ChB, FRACP

  4. Colorectal Surgical Unit, Auckland City Hospital, Auckland, New Zealand

    Bryan Parry MD, FRACS

  5. Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA

    Matthew F. Kalady MD

  6. Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, VIC, Australia

    Finlay A. Macrae MBBS, MD, FRACP, FRCP, AGAF

  7. Denver VA Medical Center, School of Medicine, University of Colorado, Denver, CO, USA

    Dennis J. Ahnen MD, AGAF

  8. Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA, Australia

    Graeme P. Young MBBS, MD, FRACP, FTSE, AGAF

  9. Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Parkville, VIC, Australia

    Lara Lipton PhD, FRACP

  10. Department of Medicine, The University of Melbourne, Parkville, VIC, Australia

    Ingrid Winship MB ChB, MD, FRACP

  11. Genetic Medicine, The Royal Melbourne Hospital, Parkville, VIC, Australia

    Ingrid Winship MB ChB, MD, FRACP

  12. Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia

    Alex Boussioutas MBBS, PhD, FRACP

  13. Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

    Alex Boussioutas MBBS, PhD, FRACP

  14. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia

    Alex Boussioutas MBBS, PhD, FRACP

  15. Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, QLD, Australia

    Joanne P. Young PhD & Daniel D. Buchanan PhD

  16. University of Hawaii Cancer Center, Honolulu, HI, USA

    Loïc Le Marchand MD, PhD

  17. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Polly A. Newcomb PhD

  18. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    Robert W. Haile DrPH

  19. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA

    Noralane M. Lindor MD

  20. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Steven Gallinger MD, MSc, FRCSC

  21. Cancer Care Ontario, Toronto, ON, Canada

    Steven Gallinger MD, MSc, FRCSC

Authors
  1. Aung Ko Win MBBS, MPH
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  2. Susan Parry MB ChB, FRACP
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  3. Bryan Parry MD, FRACS
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  4. Matthew F. Kalady MD
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  5. Finlay A. Macrae MBBS, MD, FRACP, FRCP, AGAF
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  6. Dennis J. Ahnen MD, AGAF
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  7. Graeme P. Young MBBS, MD, FRACP, FTSE, AGAF
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  8. Lara Lipton PhD, FRACP
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  9. Ingrid Winship MB ChB, MD, FRACP
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  10. Alex Boussioutas MBBS, PhD, FRACP
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  11. Joanne P. Young PhD
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  12. Daniel D. Buchanan PhD
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  13. Julie Arnold RN
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  14. Loïc Le Marchand MD, PhD
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  15. Polly A. Newcomb PhD
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  16. Robert W. Haile DrPH
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  17. Noralane M. Lindor MD
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  18. Steven Gallinger MD, MSc, FRCSC
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  19. John L. Hopper PhD
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  20. Mark A. Jenkins PhD
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Corresponding author

Correspondence to Susan Parry MB ChB, FRACP.

Additional information

A. K. Win, S. Parry equally contributed to this work.

(1) 15th Annual Meeting of Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC), Montreal, Canada, Oct 10–11, 2011. Metachronous colon cancer risk following surgery for first primary rectal cancer in Lynch syndrome.

(2) Digestive Disease Week, San Diego, CA, May 19–22, 2012. Metachronous colon cancer risk following surgery for first rectal cancer in mismatch repair gene mutation carriers.

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Win, A.K., Parry, S., Parry, B. et al. Risk of Metachronous Colon Cancer Following Surgery for Rectal Cancer in Mismatch Repair Gene Mutation Carriers. Ann Surg Oncol 20, 1829–1836 (2013). https://doi.org/10.1245/s10434-012-2858-5

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  • DOI: https://doi.org/10.1245/s10434-012-2858-5

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