Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
J Thorac Oncol. 2012 May;7(5):790-8. doi: 10.1097/JTO.0b013e3182475028.
Genome-wide association studies have identified 15q25 and 5p15 as lung cancer risk chromosomal regions in whites. The genetic structures of these loci differ between Asians and whites, however, indicating the need for additional studies in Asian populations. To examine the impact of 15p25 and 5p15 on lung cancer risk and smoking intensity, we conducted a case-control study in Japanese population. We also examined whether these loci modify the effect of smoking behavior on lung cancer risk.
Subjects were 716 Japanese patients with lung cancer and 716 controls. Associations were examined by logistic regression models with adjustment for potential confounders.
We found that the variants of rs12914385 and rs931794 on 15q25 modified the effect of cumulative tobacco smoking on lung cancer risk but that these two loci showed no statistically significant main effects on lung cancer risk. Compared with never smoking without the risk allele of rs931794, odds ratio for heavy smoking without the risk allele was 4.03 (95% confidence interval: 2.45-6.62) and that with the risk allele was 8.09 (5.09-12.9), and the joint effect of rs931734 and cumulative tobacco consumption was statistically significant (pinteraction < 0.001). A similar impact was observed with rs12914385 at chromosome 15q25 (pinteraction = 0.021). Associations for the TERT-CLPM1L locus on 5p15 with lung cancer risk in Japanese patients were of a similar magnitude to those in whites.
These results support the contribution of 15q25 and 5p15 to lung cancer and indicate that the 15q25 region modifies the well-established effect of smoking on the risk of lung cancer in a Japanese population.
全基因组关联研究已经确定了 15q25 和 5p15 是白人肺癌的风险染色体区域。然而，这些基因座的遗传结构在亚洲人和白种人之间存在差异，这表明需要在亚洲人群中进行更多的研究。为了研究 15p25 和 5p15 对肺癌风险和吸烟强度的影响，我们在日本人群中进行了病例对照研究。我们还研究了这些基因座是否可以改变吸烟行为对肺癌风险的影响。
研究对象为 716 名日本肺癌患者和 716 名对照。通过调整潜在混杂因素的逻辑回归模型来检验关联。
我们发现 15q25 上的 rs12914385 和 rs931794 变体修饰了累积吸烟对肺癌风险的影响，但这两个基因座对肺癌风险没有统计学意义的主要影响。与从不吸烟且没有 rs931794 风险等位基因的人相比，没有风险等位基因的重度吸烟者的比值比为 4.03（95%置信区间：2.45-6.62），而有风险等位基因的比值比为 8.09（5.09-12.9），rs931794 和累积吸烟的联合作用具有统计学意义（p 交互 < 0.001）。在染色体 15q25 上的 rs12914385 也观察到类似的影响（p 交互=0.021）。日本患者的 5p15 上的 TERT-CLPM1L 基因座与肺癌风险的关联与白人相似。
这些结果支持 15q25 和 5p15 对肺癌的贡献，并表明 15q25 区域修饰了吸烟对日本人群肺癌风险的既定影响。
