-
摘要:目的
探讨KRT81基因3' UTR rs3660多态与肺癌遗传易感性之间的关系。
方法使用TaqMan-MGB荧光探针标记法对KRT81基因rs3660遗传变异进行基因分型。用Logistic回归计算rs3660各基因型影响非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)发病风险的OR值及95%CI。
结果KRT81基因rs3660G>C变异影响SCLC发病风险(P=0.048),但与NSCLC发病风险无关(P=0.614)。与rs3660GG基因型携带者相比,至少携带一个C等位基因者患SCLC风险显著降低(OR=0.70, 95%CI: 0.49~0.99)。吸烟分层分析显示,在不吸烟组中,至少携带一个C等位基因的非吸烟者具有较低的SCLC发病风险(OR=0.60, 95%CI: 0.36~0.99, P=0.049)。进一步以累计吸烟量来分析,未发现至少携带一个C等位基因的轻度吸烟者(或重度吸烟者)具有较低的SCLC发病风险(OR=0.61, 95%CI: 0.26~1.43, P=0.254)。
结论KRT81基因rs3660G>C变异影响SCLC发病风险,但与NSCLC发病风险无关。
Abstract:ObjectiveTo explore the association of rs3660 polymorphism in the 3′UTR of KRT81 with the susceptibility for lung cancer.
MethodsThe genotypes of rs3660 were determined by TaqMan-MGB real-time PCR. The OR and 95%CI were estimated by Logistic regression to evaluate the association of rs3660 polymorphism with the risk of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
ResultsKRT81 rs3660G > C variant affected the risk of SCLC (P=0.048), not NSCLC (P=0.614). When compared with the individuals with rs3660GG genotype, a significant decreased risk of developing SCLC was shown in C allele carriers (OR=0.70, 95%CI: 0.49-0.99). When stratified by smoking status, C allele carriers had significantly decreased risk among non-smokers (OR=0.60, 95%CI: 0.36-0.99, P=0.049). We also found that C allele carriers had no significantly decreased risk among light smokers (or heavy smokers) (OR=0.61, 95%CI: 0.26-1.43, P=0.254).
ConclusionKRT81 rs3660G > C polymorphism contributes to the risk of SCLC, not NSCLC.
-
Key words:
- KRT81 /
- Genetic variants /
- Lung cancer /
- SNP
-
-
表 1 研究对象基本特征在病例及对照组中的分布情况
Table 1 Distributions of select characteristics in cases and control subjects
表 2 KRT81 rs3660G > C变异与肺癌发病风险的关系
Table 2 Association of KRT81 rs3660G > C polymorphism with the risk of lung cancer
表 3 rs3660变异吸烟分层与小细胞肺癌发病风险的关系
Table 3 Risk of KRT81 rs3660 genotypes with SCLC by smoking status
-
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-32. doi: 10.3322/caac.21338
[2] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1): 10-29. doi: 10.3322/caac.20138
[3] Van Meerbeeck JP, Fennell DA, De Ruysscher DKM. Small-cell lung cancer[J]. The Lancet, 2011, 378(9804): 1741-55. doi: 10.1016/S0140-6736(11)60165-7
[4] Magin TM, Vijayaraj P, Leube RE. Structural and regulatory functions of keratins[J]. Exp Cell Res, 2007, 313(10): 2021-32. doi: 10.1016/j.yexcr.2007.03.005
[5] Karantza V. Keratins in health and cancer: more than mere epithelial cell markers[J]. Oncogene, 2011, 30(2): 127-38. doi: 10.1038/onc.2010.456
[6] Lee SY, Choi JE, Jeon HS, et al. A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer[J]. Ann Oncol, 2015, 26(6): 1142-8. doi: 10.1093/annonc/mdv100
[7] Campayo M, Navarro A, Vinolas N, et al. A dual role for KRT81: a miR-SNP associated with recurrence in non-small-cell lung cancer and a novel marker of squamous cell lung carcinoma[J]. PLoS One, 2011, 6(7): e22509. doi: 10.1371/journal.pone.0022509
[8] Robles A I, Ryan BM. KRT81 miR-SNP rs3660 is associated with risk and survival of NSCLC[J]. Ann Oncol, 2016, 27(2): 360-1. doi: 10.1093/annonc/mdv552
[9] Lee SY, Choi JE, Park JY. Reply to the letter to the editor ' KRT81 miR-SNP rs3660 is associated with risk and survival of NSCLC' by Robles et al[J]. Ann Oncol, 2016, 27(2): 361-3. doi: 10.1093/annonc/mdv556
[10] Moll R, Divo M, Langbein L. The human keratins: biology and pathology[J]. Histochem Cell Biol, 2008, 129(6): 705-33. doi: 10.1007/s00418-008-0435-6
[11] Xie Y, Diao L, Zhang L, et al. A miR-SNP of the KRT81 gene is associated with the prognosis of non-Hodgkin' s lymphoma[J]. Gene, 2014, 539(2): 198-202. doi: 10.1016/j.gene.2014.02.010
[12] Guan P, Yin Z, Li X, et al. Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues[J]. J Exp Clin Cancer Res, 2012, 31: 54. doi: 10.1186/1756-9966-31-54
[13] Xiong F, Wu C, Chang J, et al. Genetic variation in an miRNA-1827 binding site in MYCL1 alters susceptibility to small-cell lung cancer[J]. Cancer Res, 2011, 71(15): 5175-81. doi: 10.1158/0008-5472.CAN-10-4407
[14] Kim J S, Choi YY, Jin G, et al. Association of a common AGO1 variant with lung cancer risk: a two-stage case-control study[J]. Mol Carcinog, 2010, 49(10): 913-21. doi: 10.1002/mc.20672
[15] Shang M, Huang Y, Hu X, et al. Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population[J]. Infect Genet Evol, 2014, 28: 113-7. doi: 10.1016/j.meegid.2014.09.015
计量
- 文章访问数: 1157
- HTML全文浏览量: 286
- PDF下载量: 394