Article Text

Download PDFPDF
Original article
Association between the Lynch syndrome gene MSH2 and breast cancer susceptibility in a Canadian familial cancer registry
  1. Mira Goldberg1,
  2. Kathleen Bell1,
  3. Melyssa Aronson2,
  4. Kara Semotiuk2,
  5. Greg Pond1,
  6. Steven Gallinger3,
  7. Kevin Zbuk1
  1. 1 Department of Oncology, McMaster University, Hamilton, Canada
  2. 2 Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada
  3. 3 Division of Hepatobiliary and Pancreatic Surgical Oncology, Toronto General Hospital, Toronto, Canada
  1. Correspondence to Dr Mira Goldberg, Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton L8V5C2, Canada; mirabgoldberg{at}


Background Previous studies assessing breast cancer risk in families with Lynch syndrome (LS) have yielded conflicting results. Furthermore, conclusions are limited by small sample size and few breast cancer outcomes. This study assesses breast cancer risk in a large prospectively followed LS cohort.

Methods Pedigrees of 325 unrelated families with LS within the Familial Gastrointestinal Cancer Registry in Canada were examined for breast cancer diagnoses. Standardised incidence ratios (SIR) and lifetime cumulative incidence calculations were used to compare the incidence of breast cancer in mutation carriers with the general population.

Results Forty-one mutation carriers diagnosed with breast cancer belonging to 34 unrelated families were identified. Mean age at diagnosis was 54 years. The mutation distribution among the LS patients with breast cancer was statistically different from those without breast cancer (p=0.015), reflecting the predominance of MSH2 mutations among affected patients (74%). Eighty-eight per cent of LS families with breast cancer met Amsterdam criteria, compared with 49% of LS families without breast cancer (p=0.03). Lifetime cumulative incidence of breast cancer in female MSH2 mutation carriers in our cohort was 22% (p<0.001). The SIR for breast cancer of female MSH2 mutation carriers in our cohort was 3.11 (95% CI 1.95 to 4.71).

Conclusions An increased risk of breast cancer in MSH2 mutation carriers was demonstrated in a Canadian familial cancer registry. Women with breast cancer often had a personal and family history of multiple LS-related malignancies. These results suggest a potential role for intensified breast cancer surveillance among women with LS.

  • lynch syndrome
  • breast cancer
  • hereditary nonpolyposis colorectal cancer
  • MSH2
  • mismatch repair mutation

Statistics from


  • Contributors MG contributed to the conception of study design, data acquisition and analysis, manuscript writing and manuscript submission. KB contributed to conception of study design, data acquisition and analysis, manuscript editing and final approval. MA and KS contributed to data acquisition and interpretation, as well as manuscript editing and final approval of the manuscript. GP contributed to data analysis and interpretation, manuscript writing and revisions, as well as finalising the submitted draft. SG contributed to the conception of the work and approving the final draft prior to submission. KZ contributed to the conception of study design, data acquisition and analysis, manuscript writing, revisions and approval for final submissions. MG and KZ are responsible for the overall content as guarantors.

  • Competing interests None declared

  • Patient consent Obtained.

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

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.