BER通路中XRCC1多位点单核苷酸多态性与新疆不同民族喉癌易感性相关性研究

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背景与目的:影响肿瘤遗传易感性的修复基因主要存在修复通路碱基切除修复(base excision repair,BER)途径,而X射线交错互补修复基因1(X-ray repair cross complementing group 1,XRCC1)是BER通路中的核心基因。近几年,国内外开展了许多有关基因多态性和喉癌易感性的研究。探讨BER通路DNA修复基因XRCC1多位点单核甘酸多态性与新疆不同民族喉癌易感性关系。方法:采用患者组与对照组的研究方法,选择58例喉癌(经病理证实为鳞状细胞癌)患者和120名体检正常的健康人对照,应用Multiplex SNa Pshot技术检测DNA碱基切除修复基因XRCC1的Gln632Gln(rs3547)、Arg399Gln(rs25487)、Arg280His(rs25489)、Arg194Trp(rs1799782)位点单核苷酸多态在患者组和正常对照组中的分布情况。结果:喉癌患者组中XRCC1Arg280His(rs25489)C/T(杂合型)及T/T(突变型)基因型的比例与对照组比较差异无统计学意义(P>0.05)。喉癌患者组中XRCC1的其余3个位点Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型的比例明显高于对照组(P<0.01)。其中汉、维、哈3个民族患者组Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型比例显著高于对照组(P<0.05),携带(rs3547)C/T及T/T基因型、(rs25487)C/T及T/T基因型、(rs1799782)G/A及A/A基因型个体较携带XRCC1(rs3547)C/C基因型、(rs25487)C/C基因型、(rs1799782)G/G基因型的个体患喉鳞状细胞癌的风险升高了分别为0.96倍、1.74倍、1.39倍;1.47倍、1.32倍、0.77倍,1.49倍、1.51倍、1.56倍。结论:汉、维、哈3个民族的XRCC1 Gln632Gln、Arg399Gln、Arg280His、Arg194Trp位点的单核苷酸多态性可能与喉癌遗传性有关联且有差异,XRCC1基因中的Gln632Gln、Arg399Gln、Arg194Trp位点的突变将导致喉癌的发病风险升高。而XRCC1基因中的Arg280His位点突变与喉癌发病的差异无统计学意义,可能该位点的突变与喉癌发病无关。 BACKGROUND & OBJECTIVE: The repair genes affecting the genetic susceptibility to tumors mainly include the base excision repair (BER) pathway, and the X-ray repair cross complementing group 1 (XRCC1) The core gene in the BER pathway. In recent years, many studies on gene polymorphisms and susceptibility to laryngeal cancer have been carried out at home and abroad. To investigate the relationship between BER pathway DNA repair gene XRCC1 multilocus single nucleotide polymorphism and the susceptibility of different ethnic laryngeal cancer in Xinjiang. Methods: Fifty-eight patients with laryngeal carcinoma (pathologically confirmed squamous cell carcinoma) and 120 normal healthy controls were selected. The multiplex DNA SNa Pshot technique was used to detect DNA base excision repair gene XRCC1 Gln632Gln (rs3547), Arg399Gln (rs25487), Arg280His (rs25489), Arg194Trp (rs1799782) site SNP in patients and normal control group distribution. Results: The proportion of XRCC1Arg280His (rs25489) C / T (heterozygous) and T / T (mutant) genotypes in laryngeal cancer patients was not significantly different from the control group (P> 0.05). The remaining three sites of XRCC1 in patients with laryngeal cancer were Gln632Gln (rs3547) C / T and T / T genotypes, Arg399Gln (rs25487) C / T (heterozygous) and T / The ratio of T (mutant) genotype, Arg194Trp (rs1799782) G / A (heterozygous) and A / A (mutant) genotypes was significantly higher than that of the control group (P <0.01). The genotypes of Gln632Gln (rs3547) C / T (heterozygous) and T / T (mutant), Arg399Gln (rs25487) C / T The genotypes of Arg194Trp (rs1799782) G / A (heterozygous) and A / A (mutant) were significantly higher than those of control (P <0.05) (Rs25487) C / C genotype, rs25487 C / T genotype, rs1799782 G / A genotype and A / A genotype were significantly higher than those with XRCC1 (rs3547) C / C genotype (Rs1799782) individuals with G / G genotype had an increased risk of laryngeal squamous cell carcinoma of 0.96 times, 1.74 times, 1.39 times, 1.47 times, 1.32 times, 0.77 times, 1.49 times, 1.51 times, 1.56 Times CONCLUSION: The single nucleotide polymorphisms of XRCC1 Gln632Gln, Arg399Gln, Arg280His and Arg194Trp in Han, Uygur and Kazak nationalities may be related to the genetic variation of laryngeal cancer. The polymorphisms of Gln632Gln, Arg399Gln, Arg194Trp in XRCC1 Site mutations will lead to an increased risk of laryngeal cancer. However, there was no significant difference between the mutation of Arg280His site and the incidence of laryngeal cancer in XRCC1 gene, which may not be related to the incidence of laryngeal cancer.
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