ArticleGenome medicine2020
Ancestry-specific predisposing germline variants in cancer.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.Frontiers in genetics · 2023Pooled it
- BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis.British journal of cancer · 2022Pooled it
- Quantifying rate-limiting genetic variation in breast and ovarian tumourigenesis.EBioMedicine · 2026Article
- Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.Frontiers in genetics · 2026Review
- Genomic and epigenomic diversity of breast cancer across Western and MENA populations: implications for precision oncology.Frontiers in oncology · 2026Review
- Widespread Epistasis between Cancer Driver Mutations and Allele-Specific Copy Number Variations.bioRxiv : the preprint server for biology · 2025Article
- Germline rare variants in cancer susceptibility genes and subsequent neoplasm risk after childhood cancer.Journal of the National Cancer Institute · 2025Article
- Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population.British journal of cancer · 2025Article
- Comparative insight: hereditary colorectal cancer registries in Iran, Singapore, and South Africa.Familial cancer · 2025Article
- Summary of radiation effects on incidence of solid cancers in the Life Span Study of atomic bomb survivors: 1958-2009.Carcinogenesis · 2025Article
- Pan-Cancer Exome-wide analysis of germline mutational patterns and pathways.Scientific reports · 2025Article
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- Germline determinants of aberrant signaling pathways in cancer.NPJ precision oncology · 2024Article
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- Onco-Breastomics: An Eco-Evo-Devo Holistic Approach.International journal of molecular sciences · 2024Review
- Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors.BMC genomics · 2024Article
- Comprehensive genomic profiling of breast cancers characterizes germline-somatic mutation interactions mediating therapeutic vulnerabilities.Cell discovery · 2023Article
- Addressing the Challenge of Biomedical Data Inequality: An Artificial Intelligence Perspective.Annual review of biomedical data science · 2023Review
- Prevalence of GermlineCancers · 2023Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDistinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations.
methodsWe conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups. We also identified the predisposition-associated two-hit events and gene expression effects in tumors.
resultsGenetic ancestry analysis classified the cohort of 9899 cancer cases into individuals of primarily European (N = 8184, 82.7%), African (N = 966, 9.8%), East Asian (N = 649, 6.6%), South Asian (N = 48, 0.5%), Native/Latin American (N = 41, 0.4%), and admixed (N = 11, 0.1%) ancestries. In the African ancestry, we discovered a potentially novel association of BRCA2 in lung squamous cell carcinoma (OR = 41.4 [95% CI, 6.1-275.6]; FDR = 0.002) previously identified in Europeans, along with a known association of BRCA2 in ovarian serous cystadenocarcinoma (OR = 8.5 [95% CI, 1.5-47.4]; FDR = 0.045). In the East Asian ancestry, we discovered one previously known association of BRIP1 in stomach adenocarcinoma (OR = 12.8 [95% CI, 1.8-90.8]; FDR = 0.038). Rare variant burden analysis further identified 7 suggestive associations in African ancestry individuals previously described in European ancestry, including SDHB in pheochromocytoma and paraganglioma, ATM in prostate adenocarcinoma, VHL in kidney renal clear cell carcinoma, FH in kidney renal papillary cell carcinoma, and PTEN in uterine corpus endometrial carcinoma. Most predisposing variants were found exclusively in one ancestry in the TCGA and gnomAD datasets. Loss of heterozygosity was identified for 7 out of the 15 African ancestry carriers of predisposing variants. Further, tumors from the SDHB or BRCA2 carriers showed simultaneous allelic-specific expression and low gene expression of their respective affected genes, and FH splice-site variant carriers showed mis-splicing of FH.
conclusionsWhile several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.
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