Hereditary breast cancer: ever more pieces to the polygenic puzzle

Bogdanova, Natalia; Helbig, Sonja; Dörk, Thilo

doi:10.1186/1897-4287-11-12

Hereditary Cancer in Clinical Practice

Table 1 Genes with intermediate to high penetrance mutations for breast cancer

From: Hereditary breast cancer: ever more pieces to the polygenic puzzle

Gene	Monoallelic mutation	Biallelic mutations	Risk for breast cancer	Reference
*BRCA1*	Breast and ovarian cancer	Microcephaly and growth disorder	high	[7, 23]
*BRCA2*	Breast and ovarian cancer	Fanconi anemia type D1	high	[8, 24]
*TP53*	Li Fraumeni Syndrome	-	high	[5, 6]
*PTEN*	PTEN harmatoma tumour syndrome (Cowden Disease)	-	high	[9, 10]
*LKB1*	Peutz-Jeghers Syndrome	-	high	[11, 12]
*MLH1*	Lynch Syndrome	-	probably intermediate (high for endometrial and colon cancer)	[13]
*MSH2*	Lynch Syndrome/Muir-Torre Syndrome	-	probably intermediate (high for endometrial and colon cancer)	[13]
*CDH1*	Lobular breast cancer, diffuse gastric cancer	-	high	[16, 17]
*PALB2*	Breast cancer	Fanconi anemia type N	intermediate to high	[25, 26]
*UIMC1*	Breast cancer¹	-	level not yet known	[27]
*FAM175A*	Breast cancer¹	-	level not yet known	[28]
*RAD51C*	Breast and ovarian cancer²	Fanconi anemia type O	low to intermediate (high for ovarian cancer)	[29, 30]
*RAD51D*	Breast and ovarian cancer²	-	low to intermediate (high for ovarian cancer)	[31, 32]
*BRIP1*	Breast and ovarian cancer	Fanconi anemia type J	low to intermediate (high for ovarian cancer)	[33, 34]
*ATM*	Breast cancer, pancreatic cancer	Ataxia telangiectasia	intermediate	[15, 35–39]
*MRE11A*	Breast cancer¹	Ataxia telangiectasia-like disorder	level not yet known	[40]
*NBN*	Breast cancer, prostate cancer	Nijmegen Breakage syndrome	intermediate	[41–43]
*RAD50*	Breast cancer	Nijmegen Breakage-like disorder	intermediate	[44]
*BLM*	Breast cancer	Bloom’s Syndrome	intermediate	[45, 46]
*FANCC*	Breast cancer¹	Fanconi anemia type C	intermediate in FA blood relatives	[47, 48]
*FANCM*	Breast cancer¹	Fanconi anemia type M	probably intermediate	[49]
*SLX4*	Breast cancer¹	Fanconi anemia type P	level not yet known	[50, 51, 84]
*XRCC2*	Breast cancer¹	-	level not yet known	[52, 82]
*CHEK2*	Breast cancer, prostate cancer	breast cancer	intermediate	[53–58]
*PPM1D*	Breast cancer³, ovarian cancer³	-	possibly intermediate (high for ovarian cancer), non-inherited	[59]

Legend to Table 1:
Twenty-five known or currently debated susceptibility genes harbouring intermediate or high risk mutations for breast cancer. Several of them give rise to developmental syndromes in the homozygous or compound heterozygous state as listed in the third column. The risk ranges for monoallelic mutations, as provided in column 4, are estimates for breast cancer from either family studies or case–control studies; intermediate risk 2–5, high risk > 5. ¹Mutations in UIMC1, FAM175A, MRE11A, FANCC, FANCM, SLX4 and XRCC2 have been observed in very few breast cancer patients so far, therefore their possible risks are yet poorly defined. ²Mutations in RAD51C and RAD51D have been observed in breast cancer patients with a family history of ovarian cancer suggesting that they are primarily ovarian cancer susceptibility genes. ³Mutations in PPM1D are non-inherited, somatic mosaic mutations that have been reported to be associated with breast and ovarian cancer.

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ISSN: 1897-4287

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