Japanese Journal of Clinical Oncology Advance Access originally published online on February 25, 2008
Japanese Journal of Clinical Oncology 2008 38(4):308-316; doi:10.1093/jjco/hyn007
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© The Author (2008). Published by Oxford University Press. All rights reserved
Lung Cancer Risk Associated with Thr495Pro Polymorphism of GHR in Chinese Population
1 Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Life Science College, Nanjing University, Nanjing
2 Department of Medicine, Jiangsu Institute of Cancer Research, Nanjing
3 The People's Hospital of Sihong, Teaching Hospital of Xuzhou Medical College, Sihong
4 Research Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
For reprints and all correspondence: Yayi Hou, Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. E-mail: yayihounju{at}yahoo.com.cn, yayihou{at}nju.edu.cn
Received August 19, 2007; accepted January 9, 2008
The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77–
). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21–3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene–environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and familial history of cancer.
Key Words: GHR • Thr495Pro polymorphism • lung cancer • MDR • molecular epidemiology