بيانات النشر: Uppsala universitet, Institutionen för immunologi, genetik och patologi
Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden.
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden.
Umeå Univ, Dept Radiat Sci Oncol, Umeå, Sweden.
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden.;Southern Alvsborg Hosp, Dept Med & Oncol, Borås, Sweden.
Karolinska Univ Hosp Solna, Hereditary Canc Unit, Stockholm, Sweden.
Linköping Univ, Dept Clin Pathol & Clin Genet, Dept Clin Expt Med, Linköping, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
Linköping Univ, Dept Clin Pathol & Clin Genet, Dept Clin Expt Med, Linköping, Sweden.;Off Med Serv Reg Skane, Dept Genet Pathol & Mol Diagnost, Lund, Sweden.
Karolinska Inst, Dept Clin Sci & Educ Sodersjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Dept Oncol, Stockholm, Sweden.
Off Med Serv Reg Skane, Dept Genet Pathol & Mol Diagnost, Lund, Sweden.;Lund Univ, Dept Lab Med, Div Clin Genet, Lund, Sweden.
نبذة مختصرة : Background: Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting. Methods: Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records. Results: In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding. Conclusions: This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer ...
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