Impact of metallothionein gene polymorphisms on the risk of lung cancer in a Japanese population

Nakane, Hideo; Hirano, Minoru; Ito, Hidemi; Hosono, Satoyo; Oze, Isao; Matsuda, Fumihiko; Tanaka, Hideo; Matsuo, Keitaro

doi:10.1002/mc.22198

Cited by 12 publications

(11 citation statements)

References 22 publications

(30 reference statements)

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“…Three loci, rs11076161 A, rs964372 C, and rs719179 C were protective against OSSC, whereas rs805239 A alleles were associated with increased risk (Zavras et al, 2011). A modest increased risk of lung cancer was associated with a polymorphism (rs7196890) in the MT1 gene, but the effect size decreased as the amount of smoking increased (Nakane et al, 2015). Thus, MT polymorphisms, particularly those in the non-coding regions of the gene, may have a role in the functionality of MT in responses to environmental agents associated with respiratory tract injuries and cancer.…”

Section: Discussionmentioning

confidence: 99%

Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice

2017

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Previous studies have suggested that oral zinc supplementation can help reduce the duration of the common cold; however, the use of intranasal (IN) zinc is strongly associated with anosmia, or the loss of the sense of smell, in humans. Prior studies from this lab showed that upregulation of metallothioneins (MT) is a rapid and robust response to zinc gluconate (ZG). Therefore, we assessed the role of MT in the recovery of nasal epithelial damage resulting from IN zinc administration. The main studies in this investigation used a high dose of ZG (170 mM) to ensure ablation of the olfactory mucosa, so that the progression of histological and functional recovery could be assessed. In vivo studies using wild-type, MT1/2 knockout mice (MT KO), and heterozygotes administered ZG by IN instillation showed profound loss of the olfactory mucosa in the nasal cavity. Recovery was monitored, and a lower percentage of the MT KO mice were able to smell 28 d after treatment; however, no significant difference was observed in the rate of cell proliferation in the basal layer of the olfactory epithelium between MT KO and wild-type mice. A lower concentration of ZG (33 mM), equivalent to that found in homeopathic IN ZG preparations, also caused olfactory epithelial toxicity in mice. These studies suggest that the use of zinc in drug formulations intended for IN administration in humans must be carefully evaluated for their potential to cause olfactory functional deficits.

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Section: Discussionmentioning

confidence: 99%

Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice

2017

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“…It is widely known that genetic factors contribute to BC susceptibility [3-7]. Recent studies showed the expression of the Metallothionein 2A ( MT2A ) gene increased in some human neoplasms [8-10]. And, it has been reported that the high expression of MT2A associated with the stage and prognosis of tumors [9, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

Liu

Wang

Tian

et al. 2017

Aging

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Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.

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“…In a Japanese population, five polymorphisms were reported to be moderately associated with the risk of lung cancer. [25] In a population from the United States, individuals with the GG and GA genotype of rs8052394 were shown to have lower hair mercury levels than those with the AA genotype. The MT1A (A>G) genotype distribution in Iran differed in comparison to those reported in Europe (P < 0.0001), [26] Spain (P < 0.0001), [24] Italy (P < 0.0001), [21,27] Bulgaria (P < 0.0001), [28] the United States (P < 0.0001), [16] China (P < 0.0001), [24] Nepal (P < 0.0001) [12] and Taiwan (P < 0.0001) [29,30] (Table 3).…”

Section: Mt1a Missense (A>g) Genotype and Allele Frequencymentioning

confidence: 99%

MT1A (A>G), MT1A (C>G), MT1M (A>C) and MT4 (G>A) single nucleotide polymorphism allele frequencies in Iranian populations

Babaei

Galehdari

Saki

2016

Biotechnology & Biotechnological Equipment

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It has been widely reported that metallothioneins (MTs) play pivotal roles in the metabolism of the relatively nontoxic essential metals, as well as of toxic heavy metals. MT gene polymorphisms in an individual may increase or decrease the expression efficiency of the gene. The present study was aimed to investigate the frequency of genetic variation of four MTs in the Iranian population. Whole blood samples were collected from 300 Iranian healthy individuals. Polymerase chain reactionÀrestriction fragment length polymorphism (PCR-RFLP) and automated Sanger sequencing were used for DNA genotype determination. The frequencies of major homozygous, heterozygous and minor homozygous genotypes in MT1 (A>G) were, respectively, 76.0%, 24.0% and 0.0%; in MT1A (C>G), 88.0%, 12.0% and 0.0%; in MT1M (A>C), 86.0%, 14.0% and 0.0%; in MT4 (G>A), 80.0%, 18.7% and 1.3%. The present study showed for the first time that the polymorphism frequency distribution of these four MTs significantly differed between the studied Iranian population and other populations around the world, except for the MT4 polymorphism in the Iranian population and populations from the USA and New Zealand, which were similar. In conclusion, it could be suggested that regional and ethnic differences are the main reasons for this varied prevalence. Ã N, number of people; major homozygote D wild type. ÃÃ P-values show whether the frequency in the Iranian population is similar to that of each respective population.

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Impact of metallothionein gene polymorphisms on the risk of lung cancer in a Japanese population

Cited by 12 publications

References 22 publications

Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice

Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

MT1A (A>G), MT1A (C>G), MT1M (A>C) and MT4 (G>A) single nucleotide polymorphism allele frequencies in Iranian populations

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