Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients
Muhammad U. Rashid
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorAnbreen Zaidi
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorDiana Torres
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorFaisal Sultan
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorAxel Benner
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Central Unit Biostatistics, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorBilal Naqvi
Marshfield Clinic Regional Cancer Center, Eau Claire, USA
Search for more papers by this authorAbdul R. Shakoori
School of Biological Sciences, Punjab University, Lahore, Pakistan
Search for more papers by this authorAntje Seidel-Renkert
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorHumirah Farooq
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorSteven Narod
Centre for Research in Women's Health, University of Toronto, Toronto, Canada
Search for more papers by this authorAsim Amin
Blumenthal Cancer Center, Carolinas Medical Center, Charlotte, USA
Search for more papers by this authorCorresponding Author
Ute Hamann
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Fax: 0049/6221/42-4721
German Cancer Research Center, Division of Molecular Genome Analysis, Im Neuenheimer Feld 580, 69120 Heidelberg, GermanySearch for more papers by this authorMuhammad U. Rashid
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorAnbreen Zaidi
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorDiana Torres
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorFaisal Sultan
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorAxel Benner
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Central Unit Biostatistics, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorBilal Naqvi
Marshfield Clinic Regional Cancer Center, Eau Claire, USA
Search for more papers by this authorAbdul R. Shakoori
School of Biological Sciences, Punjab University, Lahore, Pakistan
Search for more papers by this authorAntje Seidel-Renkert
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorHumirah Farooq
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Search for more papers by this authorSteven Narod
Centre for Research in Women's Health, University of Toronto, Toronto, Canada
Search for more papers by this authorAsim Amin
Blumenthal Cancer Center, Carolinas Medical Center, Charlotte, USA
Search for more papers by this authorCorresponding Author
Ute Hamann
Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
Fax: 0049/6221/42-4721
German Cancer Research Center, Division of Molecular Genome Analysis, Im Neuenheimer Feld 580, 69120 Heidelberg, GermanySearch for more papers by this authorAbstract
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 (≤30 years) and was 9.0% for single cases of early-onset ovarian cancer (≤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. © 2006 Wiley-Liss, Inc.
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