Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2023-10-30 DOI:10.21147/j.issn.1000-9604.2023.05.07
Zhi Li, Liming Lu, Yibin Deng, Amei Zhuo, Fengling Hu, Wanwen Sun, Guitian Huang, Linyuan Liu, Boqi Rao, Jiachun Lu, Lei Yang
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Abstract

Objective: The heightened prevalence of pulmonary nodules (PN) has escalated its significance as a public health concern. While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge, genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis. Yet, current understanding of the genetic loci associated with malignant PN (MPN) risk is limited.

Methods: A frequency-matched case-control study was performed, comprising 247 MPN cases and 412 benign NP (BNP) controls. We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort. Loci associated with MPN risk were utilized to compute a polygenic risk score (PRS). This PRS was subsequently incorporated into the diagnostic evaluation of MPNs, with emphasis on serum tumor biomarkers.

Results: Loci rs10429489G>A, rs17038564A>G, and rs12265047A>G were identified as being associated with an increased risk of MPNs. The PRS, formulated from the cumulative risk effects of these loci, correlated with the malignant risk of PNs in a dose-dependent fashion. A high PRS was found to amplify the MPN risk by 156% in comparison to a low PRS [odds ratio (OR)=2.56, 95% confidence interval (95% CI), 1.40-4.67]. Notably, the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen (CEA) in distinguishing MPNs from BPNs, with diagnostic values rising from 0.716 to 0.861 across low- to high-PRS categories. Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.

Conclusions: Loci rs10429489G>A, rs17038564A>G, and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

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肺癌的遗传易感位点与肺结节的恶性风险相关,并改善基于CEA水平的恶性诊断。
目的:肺结节(PN)的高患病率已经升级其重要性作为一个公共卫生问题。虽然准确识别恶性肿瘤的高风险PN携带者仍然是一个持续的挑战,但遗传变异具有作为疾病易感性决定因素的潜力,可以帮助诊断。然而,目前对与恶性PN (MPN)风险相关的遗传位点的了解是有限的。方法:进行频率匹配的病例对照研究,包括247例MPN病例和412例良性NP (BNP)对照。我们在一个中国队列中对11个已建立的肺癌易感位点进行了基因分型。利用与MPN风险相关的位点计算多基因风险评分(PRS)。该PRS随后被纳入mpn的诊断评估,重点是血清肿瘤生物标志物。结果:基因座rs10429489G>A、rs17038564A>G和rs12265047A>G与mpn风险增加相关。PRS是根据这些基因座的累积风险效应制定的,与PNs的恶性风险呈剂量依赖关系。研究发现,与低PRS相比,高PRS可使MPN风险增加156%[比值比(OR)=2.56, 95%可信区间(95% CI), 1.40-4.67]。值得注意的是,在区分mpn和bpn方面,PRS提高了血清癌胚抗原(CEA)的诊断准确性,在低至高PRS分类中,诊断值从0.716上升到0.861。进一步的生物信息学研究确定rs10429489G >a为表达数量性状位点。结论:rs10429489G>A、rs17038564A>G和rs12265047A>G基因座与MPN发病风险有关,可提高血清CEA浓度对MPN诊断的准确性。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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