The association of polymorphisms in DNA base excision repair genes XRCC1, OGG1 and MUTYH with the risk of childhood acute lymphoblastic leukemia

Abstract

The aim of this study was to evaluate the association of polymorphisms in genes encoding three key proteins of DNA base excision repair (BER): the OGG1 Ser326Cys, the MUTYH Tyr165Cys and the XRCC1 Arg399Gln with the risk of childhood acute lymphoblastic leukemia (ALL). Our study included 97 children patients with ALL (mean age 5.4±2.5) and 131 healthy children (mean age 6.2±2.8) used as controls. Genetic polymorphisms in BER pathway genes were examined using PCR and restriction fragment length polymorphism (RFLP). We have demonstrated that the OGG1 Cys/Cys genotype increases the risk of ALL (OR 5.36) whereas the Ser/Ser genotype variant strongly reduces the risk of this cancer among Polish children (OR 0.45). Although we did not observe the differences in single nucleotide polymorphisms (SNPs) in MUTYH and XRCC1 genes between control group and children with ALL, we have shown that the combined genotypes of examined genes can modulate the risk of childhood ALL in Polish population. We found that the combined genotype Arg/Gln-Cys/Cys of XRCC1/OGG1 (OR 3.83) as well as the Cys/Cys-Tyr/Tyr of OGG1/MUTYH (OR 6.75) increases the risk of ALL. In contrast, the combined genotype Arg/Arg-Ser/Ser of XRCC1/OGG1 (OR 0.40) as well as the Ser/Ser-Tyr/Tyr of OGG1/MUTYH (OR 0.43) played a protective role against this malignant disease. In conclusion, we suggest that polymorphisms of BER genes may be used as an important predictive factor for acute lymphoblastic leukemia in children.

Effect of ERCC1 polymorphism on the response to chemotherapy and clinical outcome of non-small cell lung cancer

“…NSCLC patients have different prognoses within the same stage, suggesting that treatments should differ based on individual genetic backgrounds. Previous studies demonstrated that polymorphic changes within several DNA repair genes may be functional and are associated with the risk of various cancers (Krupa et al, 2009;Stanczyk et al, 2011).…”

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

“…The 8-oxoguanine DNA glycosyslase (OGG1) gene encodes a DNA repair protein that removes 8-oxo-7,8-dihydroguanine (8-oxoG) [6]. The variant allele of the Ser326Cys polymorphism is associated with higher level of genetic instability and seems to be associated with an increased risk of lung, esophagus, prostate cancer as well as ALL (acute lymphoblastic leukemia) among children [7][8][9]. Opinion is divided as to whether there is an association between OGG1, Ser326Cys and colorectal cancer [8,10,11].…”

Lack of Association between the hOGG1 Ser326Cys Polymorphism and Gastric Cancer Risk: a Meta-analysis

“…Studies indicated a role of the HOGG1 Ser326Cys polymorphism in many cancers including oro-laryngeal cancer (Elahi et al, 2002;Yang et al, 2008), esophageal cancer (Xing et al, 2001), lung cancer (Lan et al, 2004), gastric cancer (Hanaoka et al, 2001), renal cell carcinoma (RCC) (Zhao et al, 2011), gallbladder cancer (Jiao et al, 2007), bladder cancer (Arizono et al, 2008), prostate cancer (Zhang et al, 2010) and acute lymphoblastic leukemia (Stanczyk et al, 2011).…”