Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk.
Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk.
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DOI：
10.3390/ijms17101597
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发表时间：
2016-09-22
影响因子：
5.6
通讯作者：
Yang K
中科院分区：
文献类型：
--
作者：
Wu X;Cheng J;Yang K
关于维生素D、维生素D代谢基因多态性、吸烟与非小细胞肺癌（NSCLC）风险之间关系的流行病学研究尚未得到全面调查。为了寻找更多的证据，利用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术和放射免疫分析法，对426例中国非小细胞肺癌患者和445例对照患者的维生素D受体（VDR）、24-羟化酶（CYP24A1）、1α-羟化酶（CYP27B1）、维生素D结合蛋白（群体特异性成分，GC）和血浆维生素D水平的5个单核苷酸多态性（SNPs）、6个单核苷酸多态性（SNPs）和2个单核苷酸多态性（SNPs）进行了评价。暴露于香烟烟雾是通过问卷信息确定的。统计分析采用多元线性回归和混合效应模型。结果显示，CYP24A1参考SNP rs6068816、VDR参考SNP rs1544410和rs731236、GC参考SNP rs7041与降低NSCLC风险有统计学意义（p < 0.001-0.05）。无论吸烟与否，非小细胞肺癌风险与血浆25-羟基维生素D [25(OH)D]总浓度之间没有明显联系。然而，CYP24A1 rs6068816和VDR rs1544410突变基因型也仅在吸烟者和非吸烟者中与25(OH)D水平升高显著相关（p < 0.01-0.05）。同时，CYP24A1纯合子rs2181874突变的吸烟者和非吸烟者的NSCLC风险显著增加(优势比(OR) = 2.14, 95%可信区间（CI） 1.47 ~ 3.43；P = 0.031；Or = 3.57, 95% ci 2.66-4.74；P = 0.019)。携带VDR纯合rs10735810突变的吸烟者患NSCLC的风险显著增加（OR = 1.93, 95% CI 1.41-2.76; p = 0.015）。然而，CYP24A1纯合子rs6068816突变的吸烟者患NSCLC的风险显著降低（OR = 0.43, 95% CI 0.27-1.02; p = 0.006）；在VDR中携带突变的纯合子rs1544410的吸烟者和非吸烟者的NSCLC风险显著降低（OR = 0.51, 95% CI 0.34-1.17; p = 0.002; OR = 0.26, 95% CI 0.20-0.69; p = 0.001）。吸烟与CYP24A1 rs2181874、CYP24A1 rs6068816、VDR rs10735810、VDR rs1544410存在显著的联合效应（p < 0.01 ~ 0.05）。携带VDR纯合rs10735810突变的吸烟者患NSCLC的风险显著增加（OR = 1.93, 95% CI 1.41-2.76; p = 0.015）。综上所述，维生素D浓度分布越低，CYP24A1、VDR和GC基因的遗传变异越可能与NSCLC风险相关。此外，吸烟和缺乏维生素D与非小细胞肺癌风险有显著的联合关系。
Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001–0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01–0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47–3.43; p = 0.031; OR = 3.57, 95% CI 2.66–4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27–1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34–1.17; p = 0.002; OR = 0.26, 95% CI 0.20–0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01–0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk.
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影响因子：
2.3
作者：
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影响因子：
30.8
作者：
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10.1016/j.jsbmb.2013.09.017
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影响因子：
4.1
作者：
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