Abstract
Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung cancer. Polymorphisms in this region are associated with risk of different cancers. To investigate the relationship between three single nucleotide polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung cancer risk, we conducted an association study in two Han Chinese populations: one population was from Zhejiang Province (576 case patients and 576 control subjects), whereas the other was from Fujian Province (576 case patients and 576 control subjects). We found that rs6983267 was significantly associated with an increased risk of lung cancer in both populations. Compared with the TT genotype, the GG genotype was associated with a significant 1.555-fold increased risk of lung cancer [95% confidence interval (CI) 1.218–1.986, P = 4.0×10−4]. This effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI 1.605–3.488, P = 1.4×10−5]. Analyses stratified by histology revealed that rs6983267 GG genotype was most associated with patients with other histological types (OR = 3.012, 95% CI 1.675–5.417, P = 2.3×10−4). The AA genotype of rs1447295 was associated with increased risk for adenocarcinoma compared with the CC genotype (OR = 2.260, 95% CI 1.174–4.353, P = 0.015). Furthermore, the GG genotype of rs6983267 was associated with worse survival in the Zhejiang population (hazard ratio (HR) = 1.646, 95% CI 1.099–2.464, P = 0.016). No association was observed for rs16901979. These results suggest that genetic variations on 8q24 may play significant roles in the development and progression of lung cancer.
Highlights
Lung cancer continues to be the leading cause of cancer-related death in both men and women worldwide
The final pooled analysis showed that the rs6983267 GG genotype (OR = 1.555, 95% confidence interval (CI) = 1.218–1.986, P = 4.061024) and GT genotype (OR = 1.311, 95% CI = 1.066–1.613, P = 0.01) were associated with significantly increased risk of lung cancer
We examined whether single-nucleotide polymorphisms (SNPs) on chromosome 8q24 related to susceptibility to breast, prostate, bladder, colorectal, thyroid, and ovarian cancers [6,7,8,9,10,11,12,13,14,15,16,23] are associated with risk of lung cancer in Han Chinese populations
Summary
Lung cancer continues to be the leading cause of cancer-related death in both men and women worldwide. In China, lung cancer accounted for 536,407 new cases of cancer and 475,768 deaths registered in 2005 [1]. Cigarette smoking is the major cause of lung cancer and contributes to more than 80% of cases [5], only a small fraction of smokers develop lung cancer. This finding indicates that genetic factors affect the risk of lung cancer. Efforts have been made to identify the genetic factors for lung cancer, current knowledge to assess lung cancer risk remains limited
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