基因多态性与吸烟和不吸烟者非小细胞肺癌风险的关联。

The association of gene polymorphisms with non-small lung cancer risk in smokers and never-smokers.

机构信息

Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

出版信息

Front Immunol. 2023 Jan 19;13:1006639. doi: 10.3389/fimmu.2022.1006639. eCollection 2022.

DOI:10.3389/fimmu.2022.1006639

PMID:36741370

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9893504/

Abstract

INTRODUCTION

Lung cancer is the predominant cause of death among cancer patients and non-small cell lung cancer (NSCLC) is the most common type. Cigarette smoking is the prevailing risk factor for NSCLC, nevertheless, this cancer is also diagnosed in never-smokers. B and T lymphocyte attenuator (BTLA) belongs to immunological checkpoints which are key regulatory molecules of the immune response. A growing body of evidence highlights the important role of BTLA in cancer. In our previous studies, we showed a significant association between gene variants and susceptibility to chronic lymphoblastic leukemia and renal cell carcinoma in the Polish population. The present study aimed to analyze the impact of polymorphic variants on the susceptibility to NSCLC and NSCLC patients' overall survival (OS).

METHODS

Using TaqMan probes we genotyped seven single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs9288953, rs1844089, rs11921669 and rs2633582 with the use of ViiA 7 Real-Time PCR System.

RESULTS

We found that rs1982809 within is associated with NSCLC risk, where carriers of rs1982809G allele (AG+GG genotypes) were more frequent in patients compared to controls. In subgroup analyses, we also noticed that rs1982809G carriers are significantly overrepresented in never-smokers, but not in smokers compared to controls. Additionally, the global distribution of the haplotypes differed between the never-smokers and smokers, where haplotypes A G G C A, C G A C G, and C G A T G were more frequent in never-smoking patients. Furthermore, the presence rs1982809G (AG+GG genotypes) allele as well as the presence of rs9288953T allele (CT+TT genotypes) increased NSCLC risk in females' patients. After stratification by histological type, we noticed that rs1982809G and rs2705511C carriers were more frequent among adenocarcinoma patients. Moreover, rs1982809G and rs2705511C correlated with the more advanced stages of NSCLC (stage II and III), but not with stage IV. Furthermore, we showed that rs2705511 and rs1982809 significantly modified OS, while rs9288952 tend to be associated with patients' survival.

CONCLUSION

Our results indicate that polymorphic variants may be considered low penetrating risk factors for NSCLC especially in never-smokers, and in females, and are associated with OS of NSCLC patients.

摘要

简介

肺癌是癌症患者死亡的主要原因，非小细胞肺癌（NSCLC）是最常见的类型。吸烟是 NSCLC 的主要危险因素，但这种癌症也发生在从不吸烟的人群中。B 和 T 淋巴细胞衰减器（BTLA）属于免疫检查点，是免疫反应的关键调节分子。越来越多的证据强调了 BTLA 在癌症中的重要作用。在我们之前的研究中，我们发现在波兰人群中，基因变异与慢性淋巴细胞白血病和肾细胞癌的易感性之间存在显著关联。本研究旨在分析多态性变异对 NSCLC 易感性和 NSCLC 患者总生存期（OS）的影响。

方法

使用 TaqMan 探针，我们使用 ViiA 7 实时 PCR 系统对七个单核苷酸多态性（SNP）：rs2705511、rs1982809、rs9288952、rs9288953、rs1844089、rs11921669 和 rs2633582 进行了基因分型。

结果

我们发现位于内的 rs1982809 与 NSCLC 风险相关，与对照组相比，rs1982809G 等位基因（AG+GG 基因型）携带者在患者中更为常见。在亚组分析中，我们还注意到 rs1982809G 携带者在从不吸烟者中明显更为常见，但在吸烟者中与对照组相比并不常见。此外，在从不吸烟者和吸烟者之间，单倍型的全球分布也不同，其中 A G G C A、C G A C G 和 C G A T G 单倍型在从不吸烟的患者中更为常见。此外，rs1982809G（AG+GG 基因型）等位基因的存在以及 rs9288953T 等位基因（CT+TT 基因型）的存在增加了女性患者的 NSCLC 风险。在按组织学类型分层后，我们注意到 rs1982809G 和 rs2705511C 携带者在腺癌患者中更为常见。此外，rs1982809G 和 rs2705511C 与 NSCLC 的更晚期（II 期和 III 期）相关，但与 IV 期无关。此外，我们发现 rs2705511 和 rs1982809 显著改变了 OS，而 rs9288952 则倾向于与患者的生存相关。