Background: The t(14;18)(q32;q21) translocation is the most commonly observed chromosomal translocation in non-Hodgkin's lymphoma (NHL), resulting in constitutive Bcl-2 expression and apoptosis inhibition. In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, has recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL.
Methods: We genotyped 226 single-nucleotide polymorphisms (SNP) from 36 candidate genes in a clinic-based study of 441 newly diagnosed NHL cases and 475 frequency-matched controls. We used principal components analysis to assess gene-level associations, and logistic regression to assess SNP-level associations. MACH was used for imputation of SNPs in BCL2L11 and CASP9.
Results: In gene-level analyses, BCL2L11 (P = 0.0019), BCLAF1 (P = 0.0097), BAG5 (P = 0.026), and CASP9 (P = 0.0022) were associated with NHL risk after accounting for multiple testing (tail strength, 0.38; 95% confidence interval, 0.05-0.70). Two of the five BCL2L11 tagSNPs (rs6746608 and rs12613243), both genotyped BCLAF1 tagSNPs (rs797558 and rs703193), the single genotyped BAG5 tagSNP (rs7693), and three of the seven genotyped CASP9 tagSNPs (rs6685648, rs2020902, and rs2042370) were significant at P < 0.05. We successfully imputed BCL2L11 and CASP9 SNPs previously linked to NHL, and replicated all four BCL2L11 and two of three CASP9 SNPs.
Conclusion: We replicated the association of BCL2L11 and CASP9 with NHL risk at the gene and SNP level, and identified novel associations with BCLAF1 and BAG5.
Impact: Closer evaluation of germline variation of genes in the apoptosis pathway with risk of NHL and its subtypes is warranted.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976783 | PMC |
| http://dx.doi.org/10.1158/1055-9965.EPI-10-0581 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Germline BRCA testing in Denmark following invasive breast cancer: Progress since 2000.
Acta Oncol
January 2025
Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Background And Purpose: Despite advancements in genetic testing and expanded eligibility criteria, underutilisation of germline testing for pathogenic variants in BRCA1 and BRCA2 (BRCA) remains evident among breast cancer (BC) patients. This observational cohort study presents real-world data on BRCA testing within the context of clinical practice challenges, including incomplete family history and under-referral.
Material And Methods: From the Danish Breast Cancer Group (DBCG) clinical database, we included 65,117 females with unilateral stage I-III BC diagnosed in 2000-2017, of whom 9,125 (14%) were BRCA tested.
Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants.
Cancer Med
February 2025
Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.
Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.
Case review of perivascular epithelioid cell tumor occurring in patients with Li-Fraumeni syndrome.
Fam Cancer
January 2025
Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Perivascular epithelioid cell tumors (PEComas) belong to a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition syndrome, is caused by a germline variant of the tumor suppressor gene TP53. Here, we report the case of a 20-year-old woman with LFS who developed a PEComa of the liver.
View Article and Find Full Text PDFJoint analysis of germline genetic data from over 29,000 cases with suspected hereditary breast and ovarian cancer (HBOC) as part of the NASGE initiative.
Breast
January 2025
Medical Genetics Center (MGZ), Bayerstr. 3-5, 80335, Munich, Germany; NASGE, Nationale Allianz für seltene genetische Erkrankungen, Germany; Department of Medicine IV, Klinikum der Universität, Ludwig-Maximilians-Universität, Ziemssenstr. 5, 80336, Munich, Germany. Electronic address:
As multigene panel testing is becoming routine in clinical care, there are recommendations at national and international level, as to which genes should be analyzed in the context of a hereditary breast and ovarian cancer (HBOC). However, the individual composition of gene panels offered by testing laboratories vary, resulting in a different variant diagnostic rate. Therefore, we performed a retrospective NGS dataset analysis of suspected HBOC patients who had been tested at different German diagnostic laboratories that are part of the NASGE network.
View Article and Find Full Text PDFAssociation of Germline Pathogenic Variants in and Other DNA Damage Response Genes With Lung Cancer Risk Among Non-Hispanic Whites and African Americans.
JCO Precis Oncol
January 2025
Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
Article Synopsis
- This study investigated the presence of rare germline variants in DNA damage response (DDR) genes among lung cancer patients and healthy controls, focusing on non-Hispanic Whites and African Americans.
- Researchers analyzed data from 3,040 participants and found that lung cancer cases had a higher occurrence of these pathogenic variants compared to controls, particularly among those with adenocarcinoma.
- The findings suggest that specific DDR gene variants are linked to lung cancer risk, especially in never smokers and those not qualifying for current screening guidelines, indicating the need for further research in these groups.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!