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


CONCLUSIONS
The common polymorphisms of the GSTP1 gene may be the candidates for SNP markers for lung cancer susceptibility in Chinese Han population.
Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China.
Jun-dong
JD
Gu
1] Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China [2] Department of Surgery Oncology, Shandong Cancer Hospital, Ji-nan 250117, China.
Feng
F
Hua
Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China.
Chao-rong
CR
Mei
Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China.
De-jie
DJ
Zheng
Department of Surgery Oncology, Shandong Cancer Hospital, Ji-nan 250117, China.
Guo-fan
GF
Wang
Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China.
Qing-hua
QH
Zhou
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D060148:HapMap Project; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
D009195:Peroxidase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi