What is the breast cancer risk associated with a heterozygous MSH6 (MutS homolog 6) gene variant c.3026A>T (p.K1009L)?

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Last updated: February 20, 2025View editorial policy

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From the Research

The MSH6 c.3026A>T (p.K1009L) variant is currently not associated with a significantly increased risk of breast cancer, and regular breast cancer screening as recommended for the general population is advised. Individuals with this specific MSH6 variant should follow standard breast cancer screening guidelines, which typically include:

  • Annual mammograms starting at age 40-45
  • Clinical breast exams every 1-3 years for women in their 20s and 30s, and annually for women 40 and older
  • Breast self-awareness and reporting any changes to a healthcare provider This recommendation is based on current evidence that the MSH6 c.3026A>T variant is classified as a variant of uncertain significance (VUS) in relation to cancer risk, as seen in studies such as 1, which found that MSH6 mutations are associated with Lynch syndrome, primarily increasing the risk for colorectal and endometrial cancers, but not conclusively linked to a significant increase in breast cancer risk.

It's essential to note that genetic knowledge evolves, and the classification of this variant may change with new research, as highlighted in studies like 2, which discussed the complexity of cancer pedigrees involving multiple cancer genes, including MSH2 and MSH6. Regular follow-ups with a genetic counselor or oncologist are recommended to stay updated on any changes in risk assessment or management recommendations. The most recent and highest quality study, 1, provides the basis for this recommendation, prioritizing morbidity, mortality, and quality of life as the outcome.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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