title: Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients.
abstract: Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of the BRCA1 and BRCA2 germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. Comprehensive BRCA mutation screening was performed using a range of techniques, including denaturing high-pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ-line mutations were identified in the 176 families (17.0%), including 23 in BRCA1 and 7 in BRCA2. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identified BRCA1 mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence of BRCA1 or BRCA2 mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early-onset breast cancer (< or =30 years) and was 9.0% for single cases of early-onset ovarian cancer (< or =45 years). Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer and early-onset breast and ovarian cancer cases in Pakistan.
authors.affiliation: Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Muhammad U
authors.initials: MU
authors.lastname: Rashid
authors.forename: Anbreen
authors.initials: A
authors.lastname: Zaidi
authors.forename: Diana
authors.initials: D
authors.lastname: Torres
authors.forename: Faisal
authors.initials: F
authors.lastname: Sultan
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Bilal
authors.initials: B
authors.lastname: Naqvi
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Shakoori
authors.forename: Antje
authors.initials: A
authors.lastname: Seidel-Renkert
authors.forename: Humirah
authors.initials: H
authors.lastname: Farooq
authors.forename: Steven
authors.initials: S
authors.lastname: Narod
authors.forename: Asim
authors.initials: A
authors.lastname: Amin
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005820:Genetic Testing; D005843:Geography; D018095:Germ-Line Mutation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010154:Pakistan; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein