The <i>APC</i> I1307K variant and male breast cancer risk: a multicenter case-control study in Italy
Abstract Objectives The APC I1307K variant is a known moderate-risk allele for colorectal cancer (CRC), especially among Ashkenazi Jewish (AJ) individuals. However, its role in other cancers, particularly in male breast cancer (MBC), remains unclear. This study aimed to evaluate whether APC I1307K contributes to MBC risk in the Italian (non-AJ) population. Methods A multicenter case-control study was conducted involving 1028 MBC cases and 2,126 geographically matched healthy male controls. Genotyping was performed via Next Generation Sequencing or TaqMan assays. Associations between APC I1307K and MBC risk were analyzed using logistic regression models, including multivariate adjustments for age, enrollment center, and BRCA1/2 status. Results The APC I1307K variant was detected in 4 MBC cases (0.4 %) and 5 controls (0.2 %). No statistically significant association with MBC risk was observed (multivariate odds ratio [OR]=3.7, 95 % CI: 0.8–17.0, p=0.09). Clinical-pathologic comparisons revealed no distinguishing features among variant carriers. None of the carriers harbored BRCA1/2 pathogenic variants (PVs) or had personal histories of CRC or familial adenomatous polyposis. Conclusions These findings suggest that APC I1307K does not confer a significant risk for MBC in the Italian population.
Authors
- Livia Manzella (ORCID: https://orcid.org/0000-0002-9908-6443)
- Valentina Zampiga (ORCID: https://orcid.org/0000-0002-7356-8153)
- Daniela Turchetti (ORCID: https://orcid.org/0000-0002-6792-3921)
- Giuseppe Giannini (ORCID: https://orcid.org/0000-0003-0299-4056)
- Valentina Arcangeli (ORCID: https://orcid.org/0000-0001-6866-2957)
- Bernardo Bonanni
- Ines Zanna (ORCID: https://orcid.org/0000-0002-5710-6506)
- Siranoush Manoukian (ORCID: https://orcid.org/0000-0002-6034-7562)
- Viviana Gismondi (ORCID: https://orcid.org/0000-0002-1115-0325)
- Marco Montagna (ORCID: https://orcid.org/0000-0002-4929-2150)
- Agostino Bucalo
- Virginia Porzio
- Giovanna Masala (ORCID: https://orcid.org/0000-0002-5758-9069)
- Laura Cortesi (ORCID: https://orcid.org/0000-0001-8950-8561)
- Valentina Silvestri (ORCID: https://orcid.org/0000-0003-0712-9379)
- Daniele Calistri
- Virginia Valentini (ORCID: https://orcid.org/0000-0003-3393-7185)
- Laura Ottini (ORCID: https://orcid.org/0000-0001-8030-0449)
- Maria Grazia Tibiletti (ORCID: https://orcid.org/0000-0001-8471-1229)
- Paolo Peterlongo (ORCID: https://orcid.org/0000-0001-6951-6855)
- Alessandra Viel
- Paolo Radice (ORCID: https://orcid.org/0000-0001-6298-4111)
- Ileana Carnevali
- Antonio Russo
Institutions
- University of Insubria (IT)
- University of Modena and Reggio Emilia (IT)
- Ospedale di Circolo e Fondazione Macchi (IT)
- Prevention Institute (US)
- University of Catania (IT)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Istituto Oncologico Veneto (IT)
- Centro di Riferimento Oncologico (IT)
- Ospedale Policlinico San Martino (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- European Institute of Oncology (IT)
- Sapienza University of Rome (IT)
- University of Palermo (IT)
- University of Bologna (IT)
Publication Details
- Journal
- ONCOLOGIE
- Published
- 2025-12-20
- DOI
- https://doi.org/10.1515/oncologie-2025-0374
- Primary Topic
- Male Breast Health Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Dipartimenti di Eccellenza
- European Commission
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Sapienza Università di Roma
- Associazione Italiana per la Ricerca sul Cancro