Screening Mammography and Breast Cancer: Variation in Risk with Rare Deleterious or Predicted Deleterious Variants in...

Area of Science:

• Genetics
• Oncology
• Radiology

Background:

• Women with a family history of breast cancer (BC) undergo earlier and more frequent screening.
• Genetic predisposition significantly influences BC risk and screening recommendations.

Purpose of the Study:

• To investigate the combined impact of mammography screening and DNA repair gene variants (excluding BRCA1/2) on breast cancer risk in high-risk women.
• To identify specific genetic profiles that may alter susceptibility to screening-related risks.

Main Methods:

• A case-control study involving 1552 BC cases and 1363 controls with hereditary predisposition.
• Analysis of germline rare deleterious or predicted deleterious variants (D-PDVs) in 113 DNA repair genes.
• Classification of genes into "Reduced", "Independent", and "Increased" risk groups based on odds ratios.

Main Results:

• Mammography exposure was not associated with overall BC risk.
• A 4% increase in BC risk per mammogram exposure was observed under linearity assumption.
• Women with D-PDVs in "Reduced" gene groups experienced doubled BC risk from mammograms compared to those in "Increased" groups.

Conclusions:

• This is the first study on the joint effect of mammograms and non-BRCA1/2 DNA repair gene variants in high-risk women.
• Findings suggest differential susceptibility to ionizing radiation from mammography based on genetic profile.
• Further research is needed to validate these findings and inform personalized screening strategies for breast cancer.