Hereditary cancer syndromes

Table 1 Health impact of major hereditary cancer genes: Frequency of pathogenic variants in non-selected subjects and oncological patients

Gene	Frequency of pathogenic variants in population	Contribution in cancer morbidity	Ref.
BRCA1	Approximately 0.1%; > 1% in some founder populations	Breast cancer: 1%-3%; High-grade serous ovarian cancer: 15%-30%	[5,6,45,230-233]
BRCA2	Approximately 0.3%; > 1% in some founder populations	Breast cancer: 1%-3%; High-grade serous ovarian cancer: 7%-12%; Prostate cancer: 2%-4%; Pancreatic cancer: 2%-3%	[5,6,45,99,102,112,232,233]
PALB2	Approximately 0.1%	Breast cancer: Approximately 0.5%-1%	[5,6,45]
CHEK2	0.5%-0.7%	Breast cancer: 0.5%-2%; Moderately elevated frequencies across several cancer types	[5,6,25,113,234,235]
ATM	0.3%-0.5%	Breast cancer: 0.5%-0.8%; Moderately elevated frequencies across several cancer types	[5,6,45,99,102,113]
MLH1, MSH2, MSH6, PMS2, EPCAM	0.02%-0.05% for MLH1, MSH2, MSH6, EPCAM each; approximately 0.1% for PMS2	Colorectal cancer: 1%-6%; Endometrial cancer: 2%-6%	[5,6,76,236-238]
CDH1	< 0.005%	Diffuse gastric cancer: 7%; Lobular breast cancer: 0.3%	[5,6,92]
TP53	< 0.01%	Breast cancer in women < 30 years old: 2%-6%; Pediatric cancers: 8%; Osteosarcoma: 4%	[161,239,240]
HOXB13	0.2%-0.4%	Prostate cancer: Approximately 1%	[112,117,241]