Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer

Anna Krześlak,Magdalena Bryś,Hanna Romanowicz-Makowska,Beata Smolarz,Paweł Jóźwiak,Agnieszka Szymczyk,Waldemar Różański,Ewa Forma

doi:10.1007/s10238-012-0215-4

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, p dominant <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.

Highlights

Metallothioneins (MTs) are a family of proteins with low molecular mass (6–7 kDa), high content of cysteine and complete absence of aromatic amino acids [1,2,3]
We carried out an association study to examine whether MT2A gene polymorphisms are associated with risk of breast cancer
Participants who reported smoking at least 100 cigarettes in their lifetime and who had not been smoking for at least 3 months were defined as former smoker

Summary

Introduction

Metallothioneins (MTs) are a family of proteins with low molecular mass (6–7 kDa), high content of cysteine and complete absence of aromatic amino acids [1,2,3]. Apart from their role in protection of tissue against heavy metals, MTs can act as potent antioxidants against oxidative damages [1,2,3,4] They are known to participate in cell proliferation and apoptosis which are very important processes in carcinogenesis [5,6,7]. Immunohistochemical studies have shown that cytoplasmic and/or nuclear MT1/2 protein expression is associated with tumor grade, increased recurrence rate and poor survival in the highly malignant invasive ductal breast carcinomas [5, 7, 9, 10]. We comprehensively evaluated the association of this SNP with breast cancer risk in a Polish population-based case–control study

Materials and methods

Results and discussion

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