SULT1A1 gene deletion in BRCA2‐associated male breast cancer: a link between genes and environmental exposures?

Journal of Cellular and Molecular Medicine

Domenico Palli³  Piera Rizzolo¹  Ines Zanna³  Valentina Silvestri¹  Calogero Saieva³  Mario Falchetti¹  Anna Sara Navazio¹  Veronica Graziano¹  Giovanna Masala³  Simonetta Bianchi²  Antonio Russo⁵  Stefania Tommasi⁴ 

[1] Department of Molecular Medicine, “Sapienza” University of Rome, Roma, Italy;Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, AOU Careggi, University of Florence, Florence, Italy;Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy;Clinical Experimental Oncology Laboratory, National Cancer Centre of Bari, Bari, Italy;Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy

关键词: SULT1A1;    copy number variations (CNVs);    BRCA2;    male breast cancer;   

DOI  :  10.1111/jcmm.12043

来源: Wiley

【 摘 要 】

Abstract

SULT1A1, a member of sulfotransferase superfamily, is a drug and hormone metabolizing enzyme involved in the metabolism of a variety of potential mammary carcinogens of endogenous and exogenous origin. Interestingly, the metabolic activity of SULT1A1 can be affected by variations in gene copy number. Male Breast Cancer (MBC) is a rare disease and less investigated disease compared to female BC (FBC). As in FBC, the concurrent effects of genetic risk factors, particularly BRCA2 mutations, increased exposure to estrogens and environmental carcinogens play a relevant role in MBC. By quantitative real-time PCR with TaqMan probes, we investigated the presence of SULT1A1 gene copy number variations (CNVs) in a series of 72 MBCs. SULT1A1 gene deletion was observed in 10 of the 72 MBCs (13.9%). In a multivariate analysis association between BRCA2 mutation and SULT1A1 gene deletion emerged (p = 0.0005). Based on the evidence that the level of SULT1A1 enzyme activity is correlated with CNV, our data suggest that in male breast tumors SULT1A1 activity may be decreased. Thus, it can be hypothesized that in a proportion of MBCs, particularly in BRCA2-associated MBCs, the level of estrogens and environmental carcinogens exposure might be increased suggesting a link between gene and environmental exposure in the pathogenesis of MBC.

【 授权许可】

CC BY   
© 2013 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.