Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA 98109-1024, USA.
Cancer Causes Control. 2011 Mar;22(3):449-61. doi: 10.1007/s10552-010-9716-1. Epub 2011 Jan 13.
Studying gene-environment interactions may provide insight about mechanisms underpinning the reported association between chromosome 15q24-25.1 variation and lung cancer susceptibility.
In a nested case-control study comparing 746 lung cancer cases to 1,477 controls, all of whom were non-Hispanic white smokers in the β-Carotene and Retinol Efficacy Trial, we examined whether lung cancer risk is associated with single nucleotide polymorphisms (SNPs) tagging the AGPHD1, CHRNA5, CHRNA3, and CHRNB4 genes and whether such risk is modified by diet and other characteristics. Intake of fruits and vegetables, their botanical groups, and specific nutrients were ascertained generally at baseline by food-frequency questionnaire.
Several sets of SNPs in high linkage disequilibrium were found: one set associated with a 27-34% increase and two sets associated with a 13-19% decrease in risk per minor allele. Associations were most prominent for the set including the non-synonymous SNP rs16969968. The rs16969968-lung cancer association did not differ by intake level of most dietary factors examined, but was stronger for individuals diagnosed at < 70 years of age or having a baseline smoking history of <40 cigarette pack-years.
Our data suggests that diet has little influence on the relation between chromosome 15q24-25.1 variation and lung cancer risk.
研究基因-环境相互作用可能有助于深入了解报道的 15q24-25 染色体变异与肺癌易感性之间的关联的潜在机制。
在一项巢式病例对照研究中，我们比较了 746 例肺癌病例和 1477 例对照，所有研究对象均为β-胡萝卜素和视黄醇疗效试验中的非西班牙裔白种吸烟者，我们研究了肺癌风险是否与标记 AGPHD1、CHRNA5、CHRNA3 和 CHRNB4 基因的单核苷酸多态性（SNP）相关，以及这种风险是否受到饮食和其他特征的影响。一般来说，通过食物频率问卷在基线时确定水果和蔬菜及其植物群以及特定营养素的摄入量。
发现了几组高度连锁不平衡的 SNP：一组 SNP 与每个次要等位基因增加 27-34%的风险相关，两组 SNP 与风险降低 13-19%相关。与非同义 SNP rs16969968 相关的 SNP 关联最为显著。rs16969968 与肺癌的关联不因所研究的大多数饮食因素的摄入水平而异，但在诊断年龄<70 岁或基线吸烟史<40 包年的个体中更强。
我们的数据表明，饮食对 15q24-25 染色体变异与肺癌风险之间的关系影响不大。
