title: BRCA1 and BRCA2 sequence variants in Chinese breast cancer families.
abstract: A series of 45 high-risk breast cancer patients, consisting of 25 affected individuals from 16 families in China with at least two cases of breast cancer and 20 cases of breast cancer diagnosed under age 35 without reported family history, were studied for germline mutations of the BRCA1 and BRCA2 genes. Thirteen of the 16 families contained at least one case diagnosed under age 50. Three distinct protein truncating sequence variants, likely to be disease-associated, were identified: two novel mutations in BRCA1 (1584G>T and 5028delC), and a previously reported mutation in BRCA2 (7883delTTAA). Additional sequence variants identified included common polymorphisms, and several variants of unknown clinical significance, including a novel BRCA1 alteration. Based on models for predictive testing using allele frequencies and risks estimated in Western populations, our results suggest that BRCA1/2 mutations account for a somewhat smaller fraction of breast cancer cases in Tianjin than in the Caucasian populations studied. This difference could be the result of a lower penetrance of BRCA1/2 mutations due to the surrounding environmental and hormonal milieu, or a lower frequency of mutations in this population. Larger, more detailed, studies will be necessary to determine which factors underlie this difference.
authors.affiliation: Breast Department Tianjin Cancer Hospital of Tianjin Medical University, Tianjin, P.R. China. xczhi@yahoo.com
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Zhi
authors.forename: Csilla
authors.initials: C
authors.lastname: Szabo
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chopin
authors.forename: Nicola
authors.initials: N
authors.lastname: Suter
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Wang
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: David
authors.initials: D
authors.lastname: Goldgar
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Shi
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm