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Open AccessArticle

BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers

1
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
2
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
3
Experimental Oncology, Center for Study of Heredo-Familial Tumors, IRCCS Istituto Tumori “Giovanni Paolo II” Bari, 70124 Bari, Italy
4
Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori “Giovanni Paolo II” Bari, 70124 Bari, Italy
5
Università Cattolica S. Cuore, 00168 Rome, Italy
6
Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
7
Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3584; https://doi.org/10.3390/cancers12123584
Received: 27 October 2020 / Revised: 24 November 2020 / Accepted: 27 November 2020 / Published: 30 November 2020
(This article belongs to the Special Issue Molecular Genetics of Breast and Ovary Cancer)
Women who inherit a BRCAmutation face a high lifetime risk of developing cancer. However, several factors, genetic and/or “environmental”, may influence BRCA penetrance. We studied in 438 women carriers of BRCA1/2 the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. The pathogenic variants were divided into loss of function (LOF) and nonsynonymous variants. Findings from this study suggest that higher insulin levels are significantly associated with BRCA LOF variants compared to nonsynonymous variant carriers. Therefore, our results support the hypothesis that the impairment of BRCA protein functions could result in a different association with “metabolic” factors, possibly due to a genetic effect on the etiology of altered response to metabolism.
Women carriers of pathogenic variants (mutations) in the BRCA1/2 genes face a high lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). However, metabolic factors may influence BRCA penetrance. We studied the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. Overall, 438 women carriers of BRCA1/2 mutations, aged 18–70, with or without a previous diagnosis of BC/OC and without metastases, who joined our randomized dietary trial, were included in the study. The pathogenic variants were divided, according to their predicted effect, into loss of function (LOF) and nonsynonymous variants. The association between metabolic exposures and variants were analyzed by a logistic regression model. LOF variant carriers showed higher levels of metabolic parameters compared to carriers of nonsynonymous variants. LOF variant carriers had significantly higher levels of plasma glucose and serum insulin than nonsynonymous variant carriers (p = 0.03 and p < 0.001, respectively). This study suggests that higher insulin levels are significantly associated with LOF variants. Further investigations are required to explore the association of metabolic factors with LOF variants and the mechanisms by which these factors may affect BRCA-related cancer risk. View Full-Text
Keywords: BRCA genes; pathogenic variants; BRCA-related cancer; metabolic factors BRCA genes; pathogenic variants; BRCA-related cancer; metabolic factors
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MDPI and ACS Style

Oliverio, A.; Bruno, E.; Colombo, M.; Paradiso, A.; Tommasi, S.; Daniele, A.; Terribile, D.A.; Magno, S.; Guarino, D.; Manoukian, S.; Peissel, B.; Radice, P.; Pasanisi, P. BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers. Cancers 2020, 12, 3584. https://doi.org/10.3390/cancers12123584

AMA Style

Oliverio A, Bruno E, Colombo M, Paradiso A, Tommasi S, Daniele A, Terribile DA, Magno S, Guarino D, Manoukian S, Peissel B, Radice P, Pasanisi P. BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers. Cancers. 2020; 12(12):3584. https://doi.org/10.3390/cancers12123584

Chicago/Turabian Style

Oliverio, Andreina; Bruno, Eleonora; Colombo, Mara; Paradiso, Angelo; Tommasi, Stefania; Daniele, Antonella; Terribile, Daniela A.; Magno, Stefano; Guarino, Donatella; Manoukian, Siranoush; Peissel, Bernard; Radice, Paolo; Pasanisi, Patrizia. 2020. "BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers" Cancers 12, no. 12: 3584. https://doi.org/10.3390/cancers12123584

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