Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

Abstract

BackgroundAcute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes.MethodsWe examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995–2002.ResultsWe found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL.ConclusionsThese results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-011-9848-y) contains supplementary material, which is available to authorized users.

Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics

“…After extraction using the QIAamp DNA Mini Kit (QIAGEN, USA, Valencia, CA), these DNA samples were whole-genome amplified using REPLI-g reagents (QIAGEN, USA, Valencia, CA). We previously genotyped DNA specimens from both buccal cells and DBS for nine subjects; genotype concordance between paired samples was 98.9 % [16]. Regardless of source, DNA specimens were quantified using human-specific Alu-PCR to confirm a minimum level of amplifiable human DNA [17] and randomized prior to genotyping.…”

CYP3A5 FNx01 3 genetic polymorphism is associated with childhood acute lymphoblastic leukemia risk: A meta-analysis

“…It is generally considered that the interaction between genetic susceptibility and environmental exposures may play an important role in the etiology of ALL. [3][4][5][6] It has been suggested that host polymorphisms may modify the individual's ability to respond to xenobiotics and maintain an intact genome in face of genotoxic stress. [7] Thus, polymorphisms in genes encoding xenobiotic-metabolizing enzymes may have determined susceptibility to cancer.…”

Association between single nucleotide polymorphisms of X-ray repair cross-complementing protein 4 gene and development of pancreatic cancer

“…Numerous epidemiologic studies have reported that XRCC4 gene polymorphisms are associated with the risk of several types of cancers, such as colorectal cancer, acute lymphoblastic leukemia, breast cancer, glioma, hepatocellular carcinoma, non-small-cell lung cancer, esophageal cancer and prostate cancer (Bau et al, 2010;Chokkalingam et al, 2011;Zhou et al, 2012;He et al, 2013;Long et al, 2013;Zhao et al, 2013;Fan et al, 2013;Shao et al, 2014). Bau et al (2010) investigated the association between XRCC4 gene polymorphisms and the susceptibility to colorectal cancer, and suggested that XRCC4 rs6869366 polymorphism may contribute to the development of esophageal cancer and may be useful for early detection of colorectal cancer.…”