Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.
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.
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia.
Aung Ko
AK
Win
Susan
S
Parry
Bryan
B
Parry
Matthew F
MF
Kalady
Finlay A
FA
Macrae
Dennis J
DJ
Ahnen
Graeme P
GP
Young
Lara
L
Lipton
Ingrid
I
Winship
Alex
A
Boussioutas
Joanne P
JP
Young
Daniel D
DD
Buchanan
Julie
J
Arnold
Loïc
L
Le Marchand
Polly A
PA
Newcomb
Robert W
RW
Haile
Noralane M
NM
Lindor
Steven
S
Gallinger
John L
JL
Hopper
Mark A
MA
Jenkins
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D002353:Carrier State; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D009520:New Zealand / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000235:genetics* / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
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