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-infinity). 
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.