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. 2012 Mar 20;30(9):958-64.
doi: 10.1200/JCO.2011.39.5590. Epub 2012 Feb 13.

Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study

Aung Ko Win  1 , Joanne P Young, Noralane M Lindor, Katherine M Tucker, Dennis J Ahnen, Graeme P Young, Daniel D Buchanan, Mark Clendenning, Graham G Giles, Ingrid Winship, Finlay A Macrae, Jack Goldblatt, Melissa C Southey, Julie Arnold, Stephen N Thibodeau, Shanaka R Gunawardena, Bharati Bapat, John A Baron, Graham Casey, Steven Gallinger, Loïc Le Marchand, Polly A Newcomb, Robert W Haile, John L Hopper, Mark A Jenkins
Affiliations

Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study

Aung Ko Win et al. J Clin Oncol. .

Abstract

Purpose: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population.

Patients and methods: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers.

Results: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97).

Conclusion: We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Flow diagram of the selection of carriers and noncarriers of a mismatch repair gene mutation. CRC, colorectal cancer; EC, endometrial cancer. (*) Although the EC risk cohort was composed of women, a note of clarification with respect to the men excluded from this group is provided.
Fig 2.
Fig 2.
Kaplan-Meier curves for cumulative risks and their corresponding 95% CIs of colorectal cancer at 5 and 10 years.
See this image and copyright information in PMC

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