Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer

Abstract

Metallothioneins (MTs) are a family of metal binding proteins that play an important role in cellular processes such as proliferation and apoptosis. Metallothionein 2A is the most expressed MT isoform in the breast cells. A number of studies have demonstrated increased MT2A expression in various human tumors, including breast cancer. We carried out an association study to examine whether MT2A gene polymorphisms are associated with risk of breast cancer. Information on lifestyle risk factors was collected via a self-administered questionnaire. Genotyping was conducted using polymerase chain reaction–restriction fragment length polymorphism technique. Three single nucleotide polymorphisms (SNP) rs28366003, rs1610216 and rs10636 were genotyped in 534 breast cancer cases and 556 population controls. One SNP in MT2A (rs28366003) showed a positive association with breast cancer. Compared with homozygous common allele carriers, heterozygous for the G variant [odds ratio (OR) = 1.92, 95 % confidence interval (CI):1.28–2.81, p trend <0.01; the OR assuming a dominant model 1.93 (95 % CI: 1.29–2.89, pdominant <0.02) after adjustment for age, family history, smoking status, BMI, menarche, parity, menopausal status and use of contraceptive and menopausal hormones] had a significantly increased risk of breast cancer in Polish population, as well as women with haplotypes, including variant allele of rs28366003 SNP (OR = 1.58, CI: 0.41–6.33, p global = 0.03). Our data suggest that the rs28366003 SNP in MT2A is associated with risk of breast cancer in Polish population.

The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues

“…The literature provides numerous studies investigating the toxic and tumorigenic potential of metallic agents, heavy metals and their compounds in cancerous diseases, which confirm their association with progression of neoplastic processes (Ahamed and Alhadlaq, 2014; Krześlak Unfortunately, despite much research on the contribution of MT2A isoforms to tumorigenesis and behavior of various human cancers as well as patient prognosis, a literature review often demonstrates contradictory results and ambiguous conclusions (Forma et al, 2012;Kita et al, 2006;Krześlak et al, 2014Krześlak et al, , 2013Mehus et al, 2014;Pedersen et al, 2009). Most studies introduce some evidence for an association of increased MT1/MT2 isoform expression in neoplastic lesions with such clinicopathological parameters as higher stage and local tumor extension, lower grade and increased patient mortality.…”

“…The importance of the relationship between MT2A SNP and aberrant expression of heavy and toxic metals in malignant or benign tumors has been investigated in only a few studies and the relationship itself remains largely unknown. Studies on various types of tumors indicate that rs28366003 plays an important role in the determination of the levels of metals such as Cd, Zn and Pb, but divergent results concerning − 5 A/G MT2A and metal toxicity can be found (Kayaalti et al, 2010(Kayaalti et al, , 2011Krześlak et al, 2014;Seibold et al, 2011).…”

“…It has been proven that the presence of singlenucleotide polymorphisms in MT genes near the TATA box, the carriage of different genotypes and the expression of various MT isoforms may affect the risk and prognosis of neoplasms of various origin (Forma et al, 2012;Kayaalti et al, 2010Kayaalti et al, , 2011Krześlak et al, 2013Krześlak et al, , 2014Mehus et al, 2014;Pedersen et al, 2009;Starska et al, 2014b). MT2A is the most widely expressed isoform (Krześlak et al, 2013(Krześlak et al, , 2014Mehus et al, 2014;Pedersen et al, 2009). The polymorphic forms of MT2A may determine the cellular activity of MTs and alter signaling pathways during tumor development and growth, contributes to deregulated cell proliferation, apoptosis, and oxidative stress (Kayaalti et al, 2010(Kayaalti et al, , 2011Raudenska et al, 2014).…”

Microarray analysis of metallothioneins in human diseases—A review

“…Using this method Krześlak et al investigated three known single nucleotide polymorphisms (SNP) of MT2A gene in patients with breast cancer [39]. They found that the rs28366003 SNP of MT2A is positively associated with breast cancer.…”

Fully automated two-step assay for detection of metallothionein through magnetic isolation using functionalized γ-Fe2O3 particles

“…MTs are overexpressed in several tumors and this overexpression is accompanied by an increased proliferation and protection against apoptosis. Therefore, MTs can be considered as a sign of worse prognosis in some malignancies [12][13][14][15]. Some previous studies showed that the MT level correlates inversely with tumor grade [16], which led us to consider the MTs as a potential cancer marker [6,7,17].…”