PURPOSE It has been estimated that 5% to 10% of cancers are due to hereditary causes. Recent data sets indicate that the incidence of hereditary cancer may be as high as 17.5% in patients with cancer, and a notable subset is missed if screening is solely by family history and current syndrome-based testing guidelines. Identification of germline variants has implications for both patients and their families. There is currently no comprehensive overview of cancer susceptibility genes or inclusion of these genes in commercially available somatic testing. We aimed to summarize genes linked to hereditary cancer and the somatic and germline panels that include such genes. METHODS Germline predisposition genes were chosen if commercially available for testing. Penetrance was defined as low, moderate, or high according to whether the gene conferred a 0% to 20%, 20% to 50%, or 50% to 100% lifetime risk of developing the cancer or, when percentages were not available, was estimated on the basis of existing literature descriptions. RESULTS We identified a total of 89 genes linked to hereditary cancer predisposition, and we summarized these genes alphabetically and by organ system. We considered four germline and six somatic commercially available panel tests and quantified the coverage of germline genes across them. Comparison between the number of genes that had germline importance and the number of genes included in somatic testing showed that many but not all germline genes are tested by frequently used somatic panels. CONCLUSION The inclusion of cancer-predisposing genes in somatic variant testing panels makes incidental germline findings likely. Although somatic testing can be used to screen for germline variants, this strategy is inadequate for comprehensive screening. Access to genetic counseling is essential for interpretation of germline implications of somatic testing and implementation of appropriate screening and follow-up.
B‐cell malignancies, most notably lymphomas, make up most of the non‐Hodgkin lymphomas in the United States. There are limited randomized data comparing first‐ and second‐generation Bruton tyrosine kinase (BTK) inhibitors. Our aim was to compare the safety profiles of first versus second‐generation BTK inhibitors. A systematic search was performed from database inception to January 13, 2020. Studies with BTK inhibitor monotherapy for the treatment of B‐cell malignancies in the adult population (>18 years old) were utilized and the adverse events (AEs) were extracted. Fifty‐five studies that met the inclusion criteria were included in the systematic review with 41 studies with first generation and 14 studies with second generation. The review included both clinical trials and retrospective studies with average time of follow‐up of 2 years for the first‐generation group and 18 months for the second‐generation group. We found that the incidence of cardiovascular AEs was significantly higher in the first‐generation group (20.8%) as compared to the second‐generation group (6.3%). However, there was a higher incidence of hematologic/oncologic and gastrointestinal side effects in the second‐generation group compared to the first (62.3% compared to 39.2% and 36.9% compared to 28.9%). The number of Grade 5 cardiovascular events (death) was same in the first‐generation group compared to the second generation. Further research is needed to develop highly selective BTK inhibitors to avoid unwanted AEs by minimizing off‐targets.
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