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Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population |
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| Authors: | Cao Guochun Lu Hongna Feng Jifeng Shu Jian Zheng Datong Hou Yayi |
| Affiliation: | 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 |
| Abstract: | The incidence of lung cancer has been increasing over recentdecades. Previous studies showed that polymorphisms of the genesinvolved in carcinogen-detoxication, DNA repair and cell cyclecontrol comprise risk factors for lung cancer. Recent observationsrevealed that the growth hormone receptor (GHR) might play importantroles in carcinogenesis and Rudd et al. found that the Thr495Propolymorphism of GHR was strongly associated with lung cancerrisk in Caucasians living in the UK (OR = 12.98, P = 0.0019,95% CI: 1.77– ). To test whether this variant of GHR wouldmodify the risk of lung cancer in Chinese population, we comparedthe polymorphism between 778 lung cancer patients and 781 healthycontrol subjects. Our results indicate that the frequency of495Thr (2.8%) allele in cases was significantly higher thanin controls (OR = 2.04, P = 0.006, 95% CI: 1.21–3.42)which indicated this allele might be a risk factor for lungcancer. Further analyses revealed Thr495Pro variant was associatedwith lung cancer in the subpopulation with higher risk for lungcancer: male subpopulation, still-smokers subpopulation andthe subpopulation with familial history of cancer. In differenthistological types of lung cancer, Thr495Pro SNP was significantlyassociated with small cell and squamous cell lung cancer, butnot with adenocarcinoma, which suggested a potential interactionbetween this polymorphism and metabolic pathways related tosmoking. The potential gene–environment interaction onlung cancer risk was evaluated using MDR software. A significantredundant interaction between Thr495Pro polymorphism and smokingdose and familial history of cancer was identified and the combinationof genetic factors and smoking status or familial history ofcancer barely increased the cancer risk prediction accuracy.In conclusion, our results suggested that the Thr495Pro polymorphismof GHR was associated with the risk of lung cancer in a redundantinteraction with smoking and familial history of cancer. |
| Keywords: | GHR Thr495Pro polymorphism lung cancer MDR molecular epidemiology |
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