RGD Reference Report - Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations.

Authors: Meijers-Heijboer, H  Van den Ouweland, A  Klijn, J  Wasielewski, M  De Snoo, A  Oldenburg, R  Hollestelle, A  Houben, M  Crepin, E  Van Veghel-Plandsoen, M  Elstrodt, F  Van Duijn, C  Bartels, C  Meijers, C  Schutte, M  McGuffog, L  Thompson, D  Easton, D  Sodha, N  Seal, S  Barfoot, R  Mangion, J  Chang-Claude, J  Eccles, D  Eeles, R  Evans, DG  Houlston, R  Murday, V  Narod, S  Peretz, T  Peto, J  Phelan, C  Zhang, HX  Szabo, C  Devilee, P  Goldgar, D  Futreal, PA  Nathanson, KL  Weber, B  Rahman, N  Stratton, MR  Stratton, Michael R 
Citation: Meijers-Heijboer H, etal., Nat Genet. 2002 May;31(1):55-9. Epub 2002 Apr 22.
RGD ID: 1599601
Pubmed: PMID:11967536   (View Abstract at PubMed)
DOI: DOI:10.1038/ng879   (Journal Full-text)

Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer susceptibilityIAGP 1599601DNA:deletion: and 1100delCRGD 
Breast Neoplasms  ISOCHEK2 (Homo sapiens)1599601; 1599601DNA:deletion: and 1100delCRGD 
Breast Neoplasms susceptibilityIDA 1599601 RGD 
male breast cancer susceptibilityIAGP 1599601DNA:deletion: :1100delCRGD 
male breast cancer susceptibilityISOCHEK2 (Homo sapiens)1599601; 1599601DNA:deletion: :1100delCRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast carcinoma susceptibilityIAGP 1599601 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Chek2  (checkpoint kinase 2)

Genes (Mus musculus)
Chek2  (checkpoint kinase 2)

Genes (Homo sapiens)
CHEK2  (checkpoint kinase 2)

QTLs
MAMTS47_H  (Mammary tumor susceptibility QTL 47 (human))


Additional Information