Association analysis of germline variants in GEN1 with a susceptibility to prostate cancer in Polish men
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Le résumé fourni par la source
BACKGROUND: The GEN1 gene is involved in DNA damage repair, as are several prostate cancer susceptibility genes, and is now included in several NGS clinical testing panels. The aim of our study was to investigate the role of GEN1 mutations in the etiology of prostate cancer. METHODS: First, we sequenced GEN1 in 390 Polish men with familial prostate cancer and 300 population controls using exome sequencing to identify protein-truncating variants and to analyze their possible association with prostate cancer risk. In addition, we performed a large association study of a recurrent frameshift variant of GEN1 (c.1929_1932delAAAG) among 5,857 men with unselected prostate cancer and 3,956 controls. We compared the clinical characteristics of prostate tumors in carriers of c.1929_1932delAAAG and in non-carriers. We conducted loss of heterozygosity (LOH) analysis at the GEN1 locus in prostate cancers from two men with the c.1929_1932delAAAG variant. To analyze survival, patients were followed from diagnosis to death for an average of 101 months. RESULTS: We detected two frameshift variants (c.2515_2519delAAGTT (p. Lys839Glufs*2), c.1539delT (p. Asp514Ilefs*13)) by sequencing the GEN1 gene of 390 Polish patients with familial prostate cancer and 300 cancer-free controls. Neither variant was associated with increased prostate cancer risk: c.2515_2519delAAGTT was detected in 20.5% of 390 cases and in 17.1% of 300 controls (p = 0.28), c.1539delT was detected in one case (0.3%) and none of the controls (p = 1.00). The GEN1 variant, c.1929_1932delAAAG (p. Lys645Cysfs*29), was observed in 13 of 5,857 (0.22%) unselected cases and 8 of 3,956 (0.20%) controls (OR = 1.10, p = 0.84). Clinical characteristics of prostate tumors in 13 carriers of c.1929_1932delAAAG and 5,844 non-carriers were similar. All-cause survival was similar for variant carriers and non-carriers (age-adjusted HR = 0.68, p = 0.76). The wild-type GEN1 allele was not lost in two prostate tumors in men with the c.1929_1932delAAAG variant. CONCLUSIONS: Our analysis suggests that GEN1 is not a prostate cancer susceptibility gene. The study has clinical implications for genetic counseling of men who tested positive for germline variants of GEN1.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Association analysis of germline variants in GEN1 with a susceptibility to prostate cancer in Polish men
- Date Crossref
- 10/06/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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International Hereditary Cancer Center pays non établi dans la noticeÉtablissement de santé
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University of Zielona Góra Department of Clinical Genetics and Pathology pays non établi dans la noticeUniversité ou école supérieure
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Pomeranian Medical University Department of Genetics and Pathology pays non établi dans la noticeUniversité ou école supérieure
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University of Toronto pays non établi dans la noticeUniversité ou école supérieure
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Women's College Hospital pays non établi dans la noticeÉtablissement de santé
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Public Health Ontario pays non établi dans la noticeÉtablissement de santé
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University Hospital in Zielona Góra Clinics of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Dalla Lana School of Public Health pays non établi dans la noticeUniversité ou école supérieure
International Hereditary Cancer Center, Department of Clinical Genetics and Pathology — University of Zielona Góra et Department of Genetics and Pathology — Pomeranian Medical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.