HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population
Abstract
Jun-dong GU1, #, Feng HUA1, 2, #, Chao-rong MEI1, De-jie ZHENG1, Guo-fan WANG2, Qing-hua ZHOU1, *
1Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China; 2Department of Surgery Oncology, Shandong Cancer Hospital, Ji-nan 250117, China
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.
Keywords: lung cancer; cancer susceptibility; carcinogen-metabolizing enzyme; MPO; GSTP1; SNP; smoking; International HapMap project; Chinese Han population
The authors thank the physicians, surgeons and pathologists at Tianjin Medical University General Hospital who endorsed the project and the patients and donors who participated in this study. This work was supported by the National “Eleventh Five-Year” Scientific and Technological Support Projects (No 2006BAI02A01).
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail zhouqinghua@lungca.org
Received 2013-11-29 Accepted 2014-01-24
Keywords:
1Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin 300052, China; 2Department of Surgery Oncology, Shandong Cancer Hospital, Ji-nan 250117, China
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.
Keywords: lung cancer; cancer susceptibility; carcinogen-metabolizing enzyme; MPO; GSTP1; SNP; smoking; International HapMap project; Chinese Han population
The authors thank the physicians, surgeons and pathologists at Tianjin Medical University General Hospital who endorsed the project and the patients and donors who participated in this study. This work was supported by the National “Eleventh Five-Year” Scientific and Technological Support Projects (No 2006BAI02A01).
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail zhouqinghua@lungca.org
Received 2013-11-29 Accepted 2014-01-24