1Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China.
2Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
DNA Cell Biol. 2019 Aug;38(8):814-823. doi: 10.1089/dna.2019.4796. Epub 2019 Jul 17.
Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723, = 0.031 and adjusted OR = 1.450, 95% CI = 1.112-1.890, = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105-3.138, = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354-3.769, = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078-1.719, = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122-1.745, = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale.
肺癌是导致高死亡率和高发病率的主要疾病之一。本研究旨在探讨中国女性人群中 miR-143/145 启动子区 rs3733845 和 rs3733846 多态性与非吸烟病例组 575 例和对照组 575 例的肺癌发病风险之间的关系。我们采用 TaqMan 等位基因鉴别法对 575 例病例和 575 例对照中 miR-143/145 启动子区的两个单核苷酸多态性（SNP）进行基因分型。采用 logistic 回归分析评估 miR-143/miR-145 启动子多态性与女性肺癌发病风险之间的关联。采用交叉分析方法探讨了这两个 SNP 与环境危险因素（油烟暴露和被动吸烟暴露）之间的交互作用。结果显示，rs3733845 和 rs3733846 多态性在显性模型中与肺腺癌风险增加相关（校正比值比[OR] = 1.329，95%置信区间[CI] = 1.026-1.723， = 0.031 和校正 OR = 1.450，95% CI = 1.112-1.890， = 0.006）。交叉分析结果表明，rs3733845 和 rs3733846 风险基因型与油烟暴露相结合，可使肺癌风险分别增加 1.862 倍和 2.260 倍（校正 OR = 1.862，95% CI = 1.105-3.138， = 0.020 用于 rs3733845；校正 OR = 2.260，95% CI = 1.354-3.769， = 0.002 用于 rs3733846）。两个 SNP 与油烟暴露之间存在正的乘法交互作用（校正 OR = 1.362，95% CI = 1.078-1.719， = 0.009 用于油 × rs3733845；校正 OR = 1.399，95% CI = 1.122-1.745， = 0.003 用于油 × rs3733846）。在非吸烟女性中，rs3733845 和 rs3733846 多态性可能与肺腺癌风险相关。此外，两个 SNP 与油烟暴露之间的交互作用在乘法尺度上而不是加法尺度上具有统计学意义。
