This retrospective study showcases the largest comprehensive characterization of the hereditary cancer genetics in India and South Asian region till date, demonstrating a substantial burden of inherited cancer susceptibility and distinct gene-cancer associations across major tumor types.
Purpose Early-onset cancers in males may indicate hereditary predisposition, yet real-world data on germline testing across diverse tumor types are limited. We evaluated the prevalence and spectrum of germline pathogenic/likely pathogenic (P/LP) variants in males diagnosed with cancer at ≤50 years. Consecutive male patients aged ≤50 years with newly diagnosed solid tumors enrolled in the Jordanian Exploratory Cancer Genetics (Jo-ECAG) program at the King Hussein Cancer Center underwent multigene panel germline testing irrespective of cancer type, stage, or family history. Patients were classified according to National Comprehensive Cancer Network (NCCN) testing criteria. P/LP and variant of uncertain significance (VUS) rates were analyzed by age, cancer type, and eligibility status. Among 652 patients (median age, 42 years), colorectal cancer predominated (48.0%), followed by gastric (6.7%), pancreatic (6.4%), and testicular (6.0%) cancers. Overall, 90 patients (13.8%) harbored P/LP variants and 216 (33.1%) had VUS. P/LP detection was higher among patients meeting NCCN criteria compared with those who did not (16.5% vs. 4.7%, p<0.001). Younger age was associated with higher yield (26.3% in ages 18–30 vs. 9.7% in 41–50 years, p<0.001). Colorectal cancer accounted for most pathogenic findings. Frequently altered genes included APC, MLH1, MSH2, MUTYH, BRCA2, and TP53; no BRCA1 P/LP variants were identified. Germline P/LP variants are common in young male patients with cancer, particularly at younger ages and among those meeting testing criteria. These findings support broader implementation of germline testing to inform management and familial risk assessment.
H. Abdel-Razeq, Hira Bani Hani, Seif Alafeef et al.· Frontiers in Oncology· 0 citations
Simple Summary Breast cancer is one of the most common cancers among women, but its genetic causes remain poorly characterized in North African populations. In this study, we investigated germline genetic variants in 165 Tunisian breast cancer patients using targeted next-generation sequencing of a multigene cancer panel. We identified pathogenic or likely pathogenic variants (P/LPVs) in BRCA1 and BRCA2 genes in 19 patients (11.5%), with several recurrent variants and additional variants not previously reported in our Tunisian cohort. P/LPV carriers were more frequently younger at diagnosis and showed significant associations with family history and several clinical features. We also identified P/LPVs in other genes. In addition, 56 variants of uncertain significance (VUS) were detected, of which 7 were prioritized through computational analyses. Additional functional or segregation evidence should be collected to establish pathogenicity. Our findings expand the available genetic data on breast cancer in Tunisia and highlight the importance of population-specific genomic studies for improving variant interpretation and genetic counseling.
N. Ammous-Boukhris, Rania Abdelmaksoud-Dammak, W. Ben Kridis et al.· Cancers· 0 citations
Background The increasing use of multigene panel testing has led to a rise in the identification of double heterozygous (DH) pathogenic variants in cancer patients, although their frequency and clinical relevance remain poorly characterised, particularly in Asian populations. Methods We conducted a retrospective review of 5,178 patients referred to a tertiary cancer genetics clinic in Singapore. DH pathogenic variants were defined as the presence of two or more distinct pathogenic or likely pathogenic germline variants identified by multigene panel testing. Clinical, pathological, and family history data were reviewed and analysed using appropriate non-parametric and exact statistical methods. Results Among 2,802 index patients with available genetic test results, 593 (21.2%) carried at least one pathogenic/likely pathogenic variant. DH pathogenic variants were identified in 21 individuals (0.75%), of which 9 were patients with breast cancer, 10 with non-breast malignancies, and 2 were cancer-free. The frequency of multiple primary cancers was 26.3% in DH variant carriers, 23.3% in single variant carriers, and 16.5% in those with no pathogenic variants. The median ages of first cancer diagnosis were 47, 44, and 48 years. Several DH combinations involved moderate- or low-penetrance genes, and some clinically unsuspected variants were detected only through broad multigene testing. Conclusion DH pathogenic variants represent a rare subgroup that is increasingly detected through multigene panel testing. Their phenotypic expression is variable, and the influence of additional pathogenic variants remains uncertain. Our findings emphasise the need for tailored genetic evaluation and further research to guide evidence-based management for this complex patient population.
R. S. J. Wong, Yi-Ong Pei, S. Ow et al.· Frontiers in Oncology· 0 citations
OBJECTIVE
The objective of this study is to investigate germline CNVs in the BRCA1 and BRCA2 genes.
MATERIALS AND METHODS
Reanalysis of whole-exome sequencing (WES) data from 140 breast cancer (BC) patients originating from Thailand's three southern border provinces was performed using the Genome Analysis Toolkit Germline Copy Number Variant (GATK-gCNV) bioinformatics pipeline. CNVs identified as positive by this pipeline were further validated through multiplex ligation-dependent probe amplification (MLPA).
RESULTS
A total of 140 individuals were diagnosed with epithelial BC. Among them, 72.86% self-identified as Muslim-Thai, while 27.14% were Buddhist-Thai. The majority of cases (60.71%) were diagnosed at or before the age of 50 years. Notably, 20% of the patients presented with triple-negative breast cancer (TNBC). All enrolled patients underwent germline CNV analysis for the BRCA1 and BRCA2 genes.
CONCLUSION
This study represents the first and largest investigation of germline CNVs in the BRCA1 and BRCA2 genes within this population. The absence of germline CNVs in both BRCA1 and BRCA2 suggests that routine screening for such alterations may be unwarranted in this specific population group.
Panupong Sukpan, Natthapon Khongcharoen, S. Samphao· Asian Pacific Journal of Can...· 0 citations
This retrospective study characterizes the prevalence and spectrum of (BReast CAncer gene 1 and 2 (
BRCA1/2)
mutations in Saudi breast and ovarian cancer patients referred for genetic testing, to define the population-specific mutational landscape. Comprehensive molecular characterization was performed on 145 blood samples from breast and ovarian cancer patients. Statistical analyses evaluated associations between mutation status and age, with significance thresholds set at p < 0.05. The overall prevalence of germline
BRCA1/2
mutations was 19.3% (28/145 samples), with
BRCA1
mutations accounting for 75% and
BRCA2
for 25%. The most frequent mutation was
BRCA1
p.(Ser1379Ter), detected in 39.3% of positive cases. Frameshift indels (71.4%) and stop-gained variants (10.7%) were predominant. Patients under 40 years showed a significantly higher mutation rate (32.9%, P=0.034).
BRCA1
mutations were more common in ovarian cancer (71.4%), while
BRCA2
variants were equally distributed between breast and ovarian cancers. This study reveals a prevalence of 19.3% for germline
BRCA1/2
mutations in the tested population, with
BRCA1
p.(Ser1379Ter) emerging as a recurrent variant, warranting further investigation as a possible founder mutation. The findings emphasize the importance of early genetic testing, particularly in younger high-risk individuals, and contribute to our understanding of
BRCA1/2
mutational patterns in breast and ovarian cancers.
Samah N. Saharti· Journal of King Saud Univers...· 0 citations
PURPOSE
Germline ATM pathogenic or likely pathogenic (P/LP) variants are increasingly recognized as clinically relevant in hereditary cancer predisposition, their integration into routine testing remains heterogeneous across countries. We describe the prevalence, tumor spectrum and relative risk associated with germline ATM P/LP variants in individuals with breast and pancreatic cancer.
METHODS
We conducted a five-year retrospective (2019-2025) reanalysis of the ATM gene in 1,707 probands tested with hereditary breast and ovarian cancer (HBOC) or pancreatic cancer panels in our center. For all probands that underwent targeted ATM reanalysis, relative risks (RR) and odds ratios (OR) were calculated. Family-based segregation was performed when possible.
RESULTS
Targeted ATM re-analysis identified 33 additional probands with P/LP variants, increasing diagnostic yield from 7.3% to 9.1% in HBOC and from 4.3% to 9.7% in pancreatic cancer. Among 22 breast-cancer probands, mean age at diagnosis was 47 years. Case-control comparison yielded OR 3.85 (95% CI 2.43-6.08; P=8.5×10-9) for breast cancer and OR 15.81 (95% CI 6.31-39.66; P=4.0×10-9) for pancreatic cancer.
CONCLUSION
This work strengthens the role of ATM in cancer predisposition panels and supports its inclusion in French national hereditary cancer panel recommendations, together with implementation of appropriate surveillance and counseling for individuals harboring ATM P/LP variants.
Iulian O. Ban, L. Mansour-Hendili, Ana María Navarro et al.· Genetics in Medicine· 0 citations
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