Document Detail

Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.
MedLine Citation:
PMID:  23358792     Owner:  NLM     Status:  MEDLINE    
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.
Aung Ko Win; Susan Parry; Bryan Parry; Matthew F Kalady; Finlay A Macrae; Dennis J Ahnen; Graeme P Young; Lara Lipton; Ingrid Winship; Alex Boussioutas; Joanne P Young; Daniel D Buchanan; Julie Arnold; Loïc Le Marchand; Polly A Newcomb; Robert W Haile; Noralane M Lindor; Steven Gallinger; John L Hopper; Mark A Jenkins
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-29
Journal Detail:
Title:  Annals of surgical oncology     Volume:  20     ISSN:  1534-4681     ISO Abbreviation:  Ann. Surg. Oncol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-17     Completed Date:  2013-12-23     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  9420840     Medline TA:  Ann Surg Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1829-36     Citation Subset:  IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics
Adenosine Triphosphatases / genetics
Australia / epidemiology
Canada / epidemiology
Carrier State*
Colonic Neoplasms / epidemiology*,  genetics*,  pathology
DNA Repair Enzymes / genetics
DNA-Binding Proteins / genetics
Kaplan-Meier Estimate
Middle Aged
MutS Homolog 2 Protein / genetics
Neoplasms, Second Primary / epidemiology*,  genetics*,  pathology
New Zealand / epidemiology
Nuclear Proteins / genetics
Proportional Hazards Models
Rectal Neoplasms / genetics*,  surgery
Retrospective Studies
Risk Factors
United States / epidemiology
Young Adult
Grant Support
CA-95-011/CA/NCI NIH HHS; U01 CA074783/CA/NCI NIH HHS; U01 CA074783/CA/NCI NIH HHS; U01 CA074794/CA/NCI NIH HHS; U01 CA074794/CA/NCI NIH HHS; U01 CA074799/CA/NCI NIH HHS; U01 CA074799/CA/NCI NIH HHS; U01 CA074800/CA/NCI NIH HHS; U01 CA074800/CA/NCI NIH HHS; U01 CA074806/CA/NCI NIH HHS; U01 CA074806/CA/NCI NIH HHS; U01 CA097735/CA/NCI NIH HHS; U01 CA097735/CA/NCI NIH HHS
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/DNA-Binding Proteins; 0/G-T mismatch-binding protein; 0/MLH1 protein, human; 0/Nuclear Proteins; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/PMS2 protein, human; EC protein, human; EC Homolog 2 Protein; EC 6.5.1.-/DNA Repair Enzymes

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