Vitamin D Receptor Gene Polymorphism: Association with Susceptibility to Early-Onset Breast Cancer in Iranian, BRCA1/2-Mutation Carrier and non-carrier Patients

Abstract

Mounting evidences support that vitamin D insufficiency or deficiency is a risk factor of breast cancer. Vitamin D receptor (VDR) is expressed in more than 36 cell types in different organs as in cancerous cells. Numerous allelic variants of VDR gene have been identified in human populations. Association of FokI (rs2228570) and BsmI (rs1544410) single nucleotide polymorphisms (SNPs) in VDR gene with the risk of breast cancer have been investigated in several studies, however, the published data are still inconsistent. Here, we investigated BsmI and FokI polymorphisms in Iranian young (≤ 35 years old) breast cancer patient with known BRCA1/2 germline mutations. VDR gene polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis in a cohort of 203 breast cancer patients and 214 controls from Iran. There was a significant association between the bb and Bb genotypes of the BsmI and the increased risk of breast cancer (OR 1.74, CI 1.06-2.87 and OR 2.08, CI 1.31-3.29, respectively). This association was maintained in the subgroup of BRCA1/2 mutation non carriers (OR 1.90, CI 1.15-3.20 and OR 1.75, CI 1.07-2.87 for bb and Bb genotypes respectively) and in the subgroup of BRCA1/2 mutation non-carriers with a family history of breast and/or ovarian cancer (OR 1.81, CI 1.08-3.05 and OR 1.65, CI 1.00-2.70 for bb and Bb genotypes respectively). None of the FokI homozygous or heterozygous genotypes were associated with the risk of breast cancer. In summary, the BsmI polymorphism of VDR gene may be associated with the risk of breast cancer in Iranian women.

Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk

“…9 The MTHFR rs1801133, MTHFR rs1801131, VDR ApaI (rs7975232), VDR BsmI (rs1544410), VDR TaqI (rs731236), VDR Fok1 (rs2228570), IL-16 rs4778889, and IL-16 rs11556218 are polymorphisms associated with risk of prostate, lung, breast, and ovarian cancer. 10-18…”

MICA‐129 Met/Val polymorphism could be a genetic biomarker for Familial Breast Cancer in the Tunisian population

“…Breast cancer risk in mutation carriers is modified by several risk factors that cluster in families, including genetic modifiers of risk that influence mutation penetrance (Chenevix-Trench et al, 2007). One of the major risk factors is a germline mutation in BRCA1 and BRCA2 which have an important role in hereditary breast-ovarian cancer in different populations (Abdikhakimov, Mukaddas, Bakhtiyar, & Shahlo, 2016;Celik et al, 2018;Harris, Morrow, & Bonadonna, 1993;Shahabi et al, 2017). In the Tunisian population, several studies have evaluated the association of these mutations in hereditary breast cancer patients (Belaiba et al, 2018;Fourati et al, 2014;Mahfoudh et al, 2012;Riahi et al, 2015;Troudi et al, 2008).…”

“…early-onset breast cancer, familial breast cancer, MICA, polymorphism, Tunisian population (Bleyer et al, 2008;Cancello et al, 2013;Encinas et al, 2015;Fostira et al, 2012;Szabo & King., 1995). The aetiology of this subgroup may be driven by a genetic predisposition (Augustinsson et al, 2018;Shahabi et al, 2017;Torrezan et al, 2018). In this context, many germline mutations have been identified in early-onset breast cancer.…”

Genetic and molecular biology of breast cancer among Iranian patients

“…The CYP24A1 and CYP27B1 were significantly correlated with age and stage, respectively [255]. Another groups have also shown that there was a significant correlation between VDR BsmI polymorphism and elevated BC risk [256, 257]. CYP17 is a steroid monooxygenase which is involved in synthesis of glucocorticoids and sex steroids [258, 259].…”