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.
The APC I1307K variant and male breast cancer risk: a multicenter case-control study in Italy / Bucalo, Agostino; Valentini, Virginia; Porzio, Virginia; Arcangeli, Valentina; Bonanni, Bernardo; Calistri, Daniele; Carnevali, Ileana; Cortesi, Laura; Giannini, Giuseppe; Gismondi, Viviana; Manoukian, Siranoush; Manzella, Livia; Montagna, Marco; Peterlongo, Paolo; Radice, Paolo; Russo, Antonio; Tibiletti, Maria Grazia; Turchetti, Daniela; Viel, Alessandra; Zampiga, Valentina; Zanna, Ines; Masala, Giovanna; Silvestri, Valentina; Ottini, Laura. - In: ONCOLOGIE. - ISSN 1765-2839. - (2025). [10.1515/oncologie-2025-0374]
The APC I1307K variant and male breast cancer risk: a multicenter case-control study in Italy
Bucalo, AgostinoPrimo
;Valentini, Virginia;Porzio, Virginia;Giannini, Giuseppe;Silvestri, Valentina;Ottini, Laura
2025
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
