Pakakasama Samart, Sirirat Tanasan, Kanchanachumpol Saowanee, Udomsubpayakul Umaporn, Mahasirimongkol Surakameth, Kitpoka Pimpun, Thithapandha Amnuay, Hongeng Suradej
Departments of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Rama VI Road, Rajthevi, Bangkok, Thailand.
Pediatr Blood Cancer. 2007 Jan;48(1):16-20. doi: 10.1002/pbc.20742.
Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL).
We genotyped polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and 715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP method. The allele, genotype, and haplotype frequencies of these polymorphisms were compared between cases and controls using Chi-square or Fisher's exact test. PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and XPD polymorphisms.
The frequency of XRCC1 194Trp allele in patients was significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children with ALL when compared to controls. The XRCC1 399Gln allele was associated with a significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls.
The XRCC1 194Trp allele and haplotype B showed a protective effect against development of childhood ALL. In contrast, individuals with the XRCC1 399Gln allele and haplotype C were associated with increased risk for this disease.
DNA修复基因的多态性可改变蛋白质结构，并可能损害DNA修复能力。受损DNA修复缺陷会导致基因不稳定和致癌作用。本研究旨在评估DNA修复基因多态性对儿童急性淋巴细胞白血病（ALL）风险的影响。
我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对108例ALL患儿和317名健康对照者的X射线修复交叉互补基因1（XRCC1）密码子194（精氨酸突变为色氨酸）、280（精氨酸突变为组氨酸）和399（精氨酸突变为谷氨酰胺）以及着色性干皮病D组（XPD）密码子312（天冬氨酸突变为天冬酰胺）和715（赖氨酸突变为谷氨酰胺）的多态性进行基因分型。使用卡方检验或Fisher精确检验比较病例组和对照组中这些多态性的等位基因、基因型和单倍型频率。使用PHASE计算机软件分析XRCC1和XPD多态性的估计单倍型。
患者中XRCC1 194色氨酸等位基因频率显著低于对照组（优势比（OR）0.67；95%置信区间（CI），0.47 - 0.97）。携带XRCC1 194色氨酸/色氨酸基因型的个体患ALL的风险显著降低（OR 0.22；95% CI，0.05 - 0.96）。与对照组相比，ALL患儿中XRCC1单倍型B（194色氨酸-280精氨酸-399精氨酸）的频率显著降低。XRCC1 399谷氨酰胺等位基因与ALL风险显著增加相关（OR 1.67；95% CI，1.20 - 2.33）。患者中XRCC1单倍型C（194精氨酸-280精氨酸-399谷氨酰胺）的频率显著更高。病例组和对照组之间XRCC1 280（精氨酸突变为组氨酸）、XPD 312（天冬氨酸突变为天冬酰胺）或XPD 715（赖氨酸突变为谷氨酰胺）的等位基因频率没有差异。
XRCC1 194色氨酸等位基因和单倍型B对儿童ALL的发生具有保护作用。相反，携带XRCC1 399谷氨酰胺等位基因和单倍型C的个体患该病的风险增加。
