Myeloperoxidase G-463A polymorphism and lung cancer: A HuGE Genetic Susceptibility to Environmental Carcinogens pooled analysis

Taioli, Emanuela; Benhamou, Simone; Bouchardy, Christine; Cascorbi, Ingolf; Cajas-Salazar, Nohelia; Dally, Heike; Fong, Kwun M.; Larsen, Jill E.; Marchand, Loı̈c Le; London, Stephanie J.; Risch, Angela; Spitz, Margaret R.; Stücker, Isabelle; Weinshenker, Brian G.; Wu, Xifeng; Yang, Ping

doi:10.1097/gim.0b013e31803068b1

Cited by 44 publications

(26 citation statements)

References 46 publications

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“…The possible mechanism by which rs2333227 may affect lung cancer risk is to decrease MPO gene expression by destroying a transcript-binding site. Rs2333227 has been investigated extensively for the association with lung cancer risk, and a recent pooled-analysis indicated that the association did exist, although with weak significance [11,[27][28][29][30][31][32][33] . Hence, we did not choose this SNP for the present study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, recent research has shown that MPO may play a major role during pulmonary carcinogenesis, such as the inhibition of nucleotide excision repair in human pulmonary epithelial cells [8] , DNA damage caused by hypochlorous acid and other reactive oxygen species [9] and the methylation of P16 [10] . Clinical and epidemiological studies on the association between the MPO G463A polymorphism and lung cancer sus-www.chinaphar.com Gu JD et al Acta Pharmacologica Sinica npg ceptibility indicate that the association exists in Caucasian and Chinese populations, although it is not significant [11] . Because both experimental and epidemiological studies indicated that MPO could play an important role in pulmonary carcinogenesis, the hypothesis that polymorphism(s) of MPO may affect lung cancer risk deserved further study, both independently and at the genome-wide level.…”

Section: Introductionmentioning

confidence: 99%

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HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

Feng

Mei

et al. 2014

Acta Pharmacol Sin

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Aim: Myeloperoxidase (MPO) and glutathione S-transferase pi 1 (GSTP1) are important carcinogen-metabolizing enzymes. The aim of this study was to investigate the association between the common polymorphisms of MPO and GSTP1 genes and lung cancer risk in Chinese Han population. Methods: A total of 266 subjects with lung cancer and 307 controls without personal history of the disease were recruited in this case control study. The tagSNPs approach was used to assess the common polymorphisms of MOP and GSTP1 genes and lung cancer risk according to the disequilibrium information from the HapMap project. The tagSNP rs7208693 was selected as the polymorphism site for MPO, while the haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174 were selected as the polymorphism sites for GSTP1. The gene polymorphisms were confirmed using real-time PCR, cloning and sequencing. Results: The four GSTP1 haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174, but not the MPO tagSNP rs7208693, exhibited an association with lung cancer susceptibility in smokers in the overall population and in the studied subgroups. When Phase 2 software was used to reconstruct the haplotype for GSTP1, the haplotype CACA (rs749174+rs1695 + rs762803+rs4891) exhibited an increased risk of lung cancer among smokers (adjust odds ratio 1.53; 95%CI 1. 04-2.25, P=0.033). Furthermore, diplotype analyses demonstrated that the significant association between the risk haplotype and lung cancer. The risk haplotypes co-segregated with one or more biologically functional polymorphisms and corresponded to a recessive inheritance model. Conclusion: The common polymorphisms of the GSTP1 gene may be the candidates for SNP markers for lung cancer susceptibility in Chinese Han population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

Feng

Mei

et al. 2014

Acta Pharmacol Sin

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“…Conceivably, inadequate SCN Ϫ levels would aggravate MPO-produced injuries in patients suffering from inflammatory diseases including asthma. MPO activity has been linked to lung cancers among smokers (49) and also implicated in the pathogenesis of many neurodegenerative diseases (50-52). We find that MPO-caused injuries to a neuronal cell line (Neuro-2A) can be greatly reduced by SCN Ϫ (Fig.…”

Section: Discussionmentioning

confidence: 99%

The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases

Szép

Lü

2009

Proc. Natl. Acad. Sci. U.S.A.

125

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Cystic fibrosis (CF) is a pleiotropic disease, originating from mutations in the CF transmembrane conductance regulator (CFTR). Lung injuries inflicted by recurring infection and excessive inflammation cause Ϸ90% of the morbidity and mortality of CF patients. It remains unclear how CFTR mutations lead to lung illness. Although commonly known as a Cl ؊ channel, CFTR also conducts thiocyanate (SCN ؊ ) ions, important because, in several ways, they can limit potentially harmful accumulations of hydrogen peroxide (H 2O2) and hypochlorite (OCl ؊ ). First, lactoperoxidase (LPO) in the airways catalyzes oxidation of SCN ؊ to tissue-innocuous hypothiocyanite (OSCN ؊ ), while consuming H2O2. Second, SCN ؊ even at low concentrations competes effectively with Cl ؊ for myeloperoxidase (MPO) (which is released by white blood cells), thus limiting OCl ؊ production by the enzyme. Third, SCN ؊ can rapidly reduce OCl ؊ without catalysis. Here, we show that SCN ؊ and LPO protect a lung cell line from injuries caused by H 2O2; and that SCN ؊ protects from OCl ؊ made by MPO. Of relevance to inflammation in other diseases, we find that in three other tested cell types (arterial endothelial cells, a neuronal cell line, and a pancreatic ␤ cell line) SCN ؊ at concentrations of >100 M greatly attenuates the cytotoxicity of MPO. Humans naturally derive SCN ؊ from edible plants, and plasma SCN ؊ levels of the general population vary from 10 to 140 M. Our findings raise the possibility that insufficient levels of antioxidant SCN ؊ provide inadequate protection from OCl ؊ , thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis, neurodegeneration, and certain cancers.hydrogen peroxide ͉ hypochlorite ͉ hypothiocyanite ͉ lactoperoxidase ͉ myeloperoxidase

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“…Recently, immunochemical studies revealed that MPO is expressed in microglia, astrocytes, and certain types of neurons, suggesting that MPO could play an important role in neurodegenerative disease ( 17 ), such as multiple sclerosis (18)(19)(20), Alzheimer's ( 21,22 ), and Parkinson's disease ( 23 ). Interestingly, MPO has even been implicated as a risk factor for some forms of cancers ( 24,25 ). Some of the earliest evidence that MPO plays a role in cardiovascular disease comes from studies showing that chlorotyrosine on LDL is increased in human vascular lesions ( 26 ).…”

Section: Mpo-mediated Ldl Malondialdehyde Formationmentioning

confidence: 99%

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

Zhang¹,

Jing²,

Shi³

et al. 2013

Journal of Lipid Research

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Myeloperoxidase G-463A polymorphism and lung cancer: A HuGE Genetic Susceptibility to Environmental Carcinogens pooled analysis

Cited by 44 publications

References 46 publications

HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

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