Evaluation of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk

Breast cancer in men is a rare and still poorly characterized disease. Inherited mutations in BRCA1, BRCA2 and PALB2 genes, as well as common polymorphisms, play a role in male breast cancer genetic predisposition. Male breast cancer is considered a hormone-dependent tumor specifically related to hyperestrogenism. Polymorphisms in genes involved in estrogen biosynthesis and metabolism pathways, such as CYP17A1 and CYP1B1, have been associated with breast cancer risk. Here, we aimed to investigate the role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk. A series of 597 male breast cancer cases and 1022 male controls, recruited within the Italian Multicenter Study on male breast cancer, was genotyped for CYP17A1 rs743572, CYP1B1 rs1056836 and rs1800440 polymorphisms by allelic discrimination real-time PCR with TaqMan probes. Associations with male breast cancer risk were estimated using logistic regression. No statistically significant associations between male breast cancer risk and the three analyzed polymorphisms emerged. Similar results were obtained also when BRCA1/2 mutational status was considered. No significant differences in the distribution of the genotypes according to estrogen receptor status emerged. In conclusion, our study, based on a large series of male breast cancer cases, is likely to exclude a relevant role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer predisposition. Overall, these results add new data to the increasing evidence that polymorphisms in these genes may not be associated with breast cancer risk.

[1]  B. Bonanni,et al.  Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy , 2019, International journal of cancer.

[2]  B. Bonanni,et al.  Contribution of MUTYH Variants to Male Breast Cancer Risk: Results From a Multicenter Study in Italy , 2018, Front. Oncol..

[3]  Helen E. Parkinson,et al.  The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019 , 2018, Nucleic Acids Res..

[4]  Sara R. Selitsky,et al.  Male breast cancer: a disease distinct from female breast cancer , 2018, Breast Cancer Research and Treatment.

[5]  Xiaofei Zhang,et al.  Association between CYP17 T-34C rs743572 and breast cancer risk , 2017, Oncotarget.

[6]  A. Yousef Male Breast Cancer: Epidemiology and Risk Factors. , 2017 .

[7]  D. Steinemann,et al.  Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores , 2017, Journal of Clinical Oncology.

[8]  P. Radice,et al.  Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: results from a multicenter study in Italy. , 2015, European journal of cancer.

[9]  E. Riboli,et al.  Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Kyung-Chul Choi,et al.  Cytochrome P450 1 family and cancers , 2015, The Journal of Steroid Biochemistry and Molecular Biology.

[11]  C. Shriver,et al.  Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy , 2015, Cancer Causes & Control.

[12]  L. Ottini Male breast cancer: a rare disease that might uncover underlying pathways of breast cancer , 2014, Nature Reviews Cancer.

[13]  S. Tommasi,et al.  Male breast cancer: genetics, epigenetics, and ethical aspects. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  E. Winer,et al.  Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  P. Radice,et al.  Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy , 2013, Breast Cancer Research and Treatment.

[16]  Francis L Martin,et al.  CYP1B1 and hormone-induced cancer. , 2012, Cancer letters.

[17]  Zhen Yang,et al.  No association between CYP17 T-34C polymorphism and breast cancer risk: a meta-analysis involving 58,814 subjects , 2010, Breast Cancer Research and Treatment.

[18]  Rong-cheng Luo,et al.  Lack of association between CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis of 22,090 cases and 28,498 controls , 2010, Breast Cancer Research and Treatment.

[19]  Yun Chen,et al.  Factors influencing the association between CYP17 T34C polymorphism and the risk of breast cancer: meta-regression and subgroup analysis , 2010, Breast Cancer Research and Treatment.

[20]  Lei Yao,et al.  No association between CYP1B1 Val432Leu polymorphism and breast cancer risk: a meta-analysis involving 40,303 subjects , 2010, Breast Cancer Research and Treatment.

[21]  T. Sergentanis,et al.  Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis , 2010, Breast Cancer Research and Treatment.

[22]  R. Scott,et al.  CYP1B1 and predisposition to breast cancer in Poland , 2007, Breast Cancer Research and Treatment.

[23]  I. Screpanti,et al.  Prevalence of BRCA1 and BRCA2 genomic rearrangements in a cohort of consecutive Italian breast and/or ovarian cancer families , 2007, Breast Cancer Research and Treatment.

[24]  S. Chanock,et al.  Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women , 2006, Pharmacogenetics and genomics.

[25]  A. Baccarelli,et al.  CYP1A1 and CYP1B1 genotypes, haplotypes, and TCDD-induced gene expression in subjects from Seveso, Italy. , 2005, Toxicology.

[26]  S. Weidlich,et al.  Proteasomal Degradation of Human CYP1B1: Effect of the Asn453Ser Polymorphism on the Post-Translational Regulation of CYP1B1 Expression , 2005, Molecular Pharmacology.

[27]  Helen Swede,et al.  Epidemiology of male breast cancer. , 2005, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[28]  C. Ulrich,et al.  Association of CYP17, CYP19, CYP1B1, and COMT Polymorphisms with Serum and Urinary Sex Hormone Concentrations in Postmenopausal Women , 2004, Cancer Epidemiology Biomarkers & Prevention.

[29]  R. Jackson,et al.  Breast cancer in men. , 2003, Annals of internal medicine.

[30]  J. Jónasson,et al.  CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status , 2003, British Journal of Cancer.

[31]  S. Singletary,et al.  Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer. , 2002, Cancer research.

[32]  K. Kurian,et al.  A polymorphism in the CYP17 gene is associated with male breast cancer , 1999 .

[33]  Ali Jad Abdelwahab Yousef Male Breast Cancer: Epidemiology and Risk Factors. , 2017, Seminars in oncology.

[34]  Jie Liu,et al.  Association between the CYP1B1 polymorphisms and risk of cancer: a meta-analysis , 2014, Molecular Genetics and Genomics.