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Grand Rounds

Is there a Genetic Link between Lynch Syndrome and Breast Cancer?

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BACKGROUND AND PURPOSE:

  • Lynch syndrome (LS) is associated with several cancer types, including colon and ovarian cancer in women (see ‘Related ObG Topics for more clinical and genetic information on LS)
  • Studies on LS and breast cancer association have been conflicting
  • Roberts et al. (Genetics in Medicine, 2017) sought to determine if there is an association between (LS) and breast cancer

METHODS:

  • Retrospective review of personal and family history with pathogenic or likely pathogenic germ-line variants in
    • MLH1
    • MSH2
    • MSH6
    • PMS2
  • Mutations were identified using multigene hereditary cancer testing
  • Standard incidence ratios (SIRs) were calculated by comparing the number of observed cancers to the number of expected cancers based on breast cancer incidence in the general population

RESULTS:

  • Data was collected from 423 women
  • Age-standardized breast cancer risks
    • MSH6: Statistically significant increased SIR  2.11; 95% CI 1.56–2.86
    • PMS2: Statistically significant increased SIR 2.92; 95% CI, 2.17–3.92
  • There was no association observed for MLH1 or MSH2

CONCLUSION:

  • Overall, breast cancer risk was twofold higher in the LS cohort but only in 2 genes, MSH6 (31.1% cumulative risk for breast cancer by age 60) and PMS2 (37.7% cumulative risk for breast cancer by age 60)
  • Women with pathogenic variants in MSH6 and PMS2 have a modest but statistically increased risk of breast cancer and may benefit from increased surveillance for breast cancer

Learn More – Primary Sources:

MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer

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Related ObG Topics:

Ovarian or Endometrial Cancer? Consider Lynch Syndrome
Obstetrics Critical Care Course
USPSTF Guidance: When to Use Medication to Reduce Breast Cancer Risk
The Exome and Exome Sequencing: Prenatal Testing Recommendations

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