Hereditary Cancer Syndromes

Study Notes

Somatic mutations occur in tumors and do not alter gene function; predictive testing is not available for class 3 and below mutations.
SNPs are prevalent across cells and may slightly increase cancer risk; future trends include polygenic risk assessments that incorporate well-known SNPs along with monogenic assessments.
Variants affecting genes like RAD51C and RAD51D show moderate cancer risk and are tested in isolation.
Polygenic risk assessments may influence penetrance for moderate risk genes alongside monogenic variations, anticipated to be available soon.
High penetrance genes, such as BRCA1, significantly increase lifetime cancer risk and impair gene function.

Less likely to reach adulthood or reproduce if severe variants manifest early; prevalence of variants may exceed 1%.
Some cancer types and age are significant when predicting pathogenic variant likelihood; DNA repair and MMR pathways play crucial roles.
Genes associated with various cancers include those related to homologous recombination and MMR pathway, notably linked with breast, prostate, and gastric cancers.
A family history (FHx) elevates cancer risk management urgency, especially regarding BRCA2.
50% inheritance chance for pathogenic variants; importance of tracing lineage, particularly for female offspring.

Small populations may have higher prevalence of pathogenic variants due to limited genetic mixing.
Ashkenazi Jewish ancestry has heightened BRCA1 and BRCA2 variant carriers: 1 in 40 compared to 1 in 500 in the general population.
Incidence of breast and ovarian cancer increases likelihood of a familial pathogenic variant, especially in young adults.

Genes can be histological indicators; for example, CDH1 is associated with invasive lobular cancer, but not invasive ductal cancer.
Certain gene expressions indicate cancer subtype risk; absence of specific proteins can signal potential pathogenic variants.
Co-existent mutations, like BRAF, assist in assessing likelihood of MMR functionality loss and determine necessity for family cancer center referrals.

MMR proteins are critical for detecting and correcting mutations; deficiency elevates neoplasia risks.
Individuals with colorectal cancer (CRC) may undergo gene testing related to high polyp and CRC risks.
For breast cancer patients, a panel of genes linked to increased breast cancer risk may be offered, with an emphasis on younger patients benefiting from early detection strategies.
Evidence suggests a survival advantage for women diagnosed with MMR tumours at a younger age.