Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility
| Autor: | Schutte, Mieke, Seal, S, Barfoot, R, Meijers-Heijboer, EJ, Wasielewski, M (Marijke), Evans, DG, Eccles, D, Meijers, C, Lohman, FP, Klijn, Jan, van den Ouweland, Ans, Breast cancer Linkage Consor.,, Futreal, PA, Nathanson, KL, Weber, BL, Easton, DF, Stratton, MR, Rahman, N |
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| Přispěvatelé: | Medical Oncology, Clinical Genetics, Pediatric Surgery, Human Genetics |
| Rok vydání: | 2003 |
| Předmět: |
Male
Breast Neoplasms Protein Serine-Threonine Kinases Biology Germline 03 medical and health sciences 0302 clinical medicine Germline mutation Breast cancer Gene Frequency SDG 3 - Good Health and Well-being Genetics Genetic predisposition medicine Humans Genetics(clinical) Genetic Predisposition to Disease Allele Risk factor skin and connective tissue diseases Allele frequency CHEK2 Germ-Line Mutation Genetics (clinical) Sequence Deletion 030304 developmental biology 0303 health sciences Base Sequence Genetic Variation medicine.disease Pedigree 3. Good health Europe Checkpoint Kinase 2 030220 oncology & carcinogenesis North America Female Oligonucleotide Probes Protein Kinases Reports |
| Zdroj: | American Journal of Human Genetics, 72, 1023-1028. Cell Press American journal of human genetics, 72(4), 1023-1028. Cell Press |
| ISSN: | 1537-6605 0002-9297 |
| Popis: | We recently reported that a sequence variant in the cell-cycle–checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer–susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants reported elsewhere, R145W and I157T with breast cancer, we screened 737 BRCA1/2-negative familial breast cancer cases from 605 families, 459 BRCA1/2-positive cases from 335 families, and 723 controls from the United Kingdom, the Netherlands, and North America. All three variants were rare in all groups, and none occurred at significantly elevated frequency in familial breast cancer cases compared with controls. These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility. |
| Databáze: | OpenAIRE |
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