Xeroderma Pigmentosum Complementation Group D Lys751Gln Research Articles

Polymorphisms in XPC and XPD genes modulate DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India.

The genetic susceptibility of individuals to the genotoxic effect of pesticides may be modulated by variations in genes involved in nucleotide excision repair (NER) pathway and therefore plays an important role in the evaluation of occupational risk. We aimed to evaluate the role of xeroderma pigmentosum complementation group C (XPC) Lys939Gln (A2920C, rs2228001), XPC Ala499Val (C2151T, rs2228000), xeroderma pigmentosum complementation group D (XPD) Asp312Asn (G23591A, rs1799793) and XPD Lys751Gln (A35931C, rs13181) in the modulation of DNA damage. A total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls) from Punjab, North-West India were recruited to study DNA damage by alkaline comet assay. Genotyping was carried out by PCR-RFLP using site-specific restriction enzymes. We found significant elevation in DNA damage parameters in pesticide-exposed agricultural workers as compared to the controls (p < 0.01). Association of comet tail length with XPC 939Gln/Gln (CC), XPD 312Asp/Asn (GA) and XPD 312Asn/Asn (AA) genotypes was observed. Frequency of cells showing DNA migration was significantly higher in exposed workers with variant XPC 939Gln/Gln (CC), XPD 312Asp/Asn (GA) and XPD 312Asn/Asn (AA) genotypes. Mean tail length was significantly increased in agricultural workers carrying XPD 312Asn/Asn (AA) genotype. Elevation in total comet DNA migration was also observed in exposed workers carrying variant XPC 939Lys/Gln (AC), XPC 939Gln/Gln (CC), XPC 499Val/Val (TT) and XPD 312Asn/Asn (AA) genotypes. Our results strongly indicate significant positive association of variant XPC and XPD genotypes with higher pesticide-induced DNA damage in North-West Indian agricultural workers.

Investigation of DNA repair genes XPD and hOGG1 in type 2 Diabetes mellitus

Increased oxidative stress in type 2 diabetes cause to the accumulation of DNA damage and results diabetic complications. Xeroderma pigmentosum complementation group D (XPD) and human oxoguanine glycosylase 1 (hOGG1) are genes involved in the repair of oxidative DNA damage. In this study, we aimed to evaluate association between XPD Lys751Gln and hOGG1 Ser326Cys polymorphisms with type 2 diabetes mellitus (T2DM) in the Turkish population. Seventy-one T2DM patients and 54 healthy individuals were incorporated into this study. DNA was extracted from whole blood. The Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) techniques were used. There was statistically significant difference between patient and control groups in the genotype distribution of XPD Lys751Gln polymorphism (p˂0.05). While the Lys/Lys genotype was found significantly higher in control group, the Lys/Gln was higher in patients. (p˂0.05). There was no significant difference between groups in the genotype distribution of hOGG1 Ser326Cys polymorphism. Despite the small number of subjects included in the study, it could be interpreted that the Lys/Gln genotype of XPD Lys751Gln polymorphism may be contributing to the development of diabetes.

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to end-stage renal disease (ESRD). We aimed to determine the association of polymorphisms in xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1) with ESRD development. Polymorphisms in XPD codons 312 and 751 and XRCC1 codon 399 were genotyped in 98 patients undergoing hemodialysis and 102 healthy controls using polymerase chain reaction and restriction fragment length polymorphism. Patients having XRCC1-399 Arg/Gln genotype or XRCC1-399 Gln/Gln genotype had a significantly higher risk of ESRD than those with XRCC1-399 Arg/Arg [odds ratio (OR): 2.48; 95% confidence intervals (CI): 1.36–4.52; p = 0.004 and OR: 4.05; 95% CI: 1.19–13.73; p = 0.03, respectively]. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls (OR: 2.22; 95% CI: 1.16–4.25; p = 0.02). Combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with Asp/Asn or Asn/Asn genotypes of XPDAsp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. Haplotypes association showed that association of Gln allele of XRCC1 Arg399Gln polymorphism with the Asn allele of XPDAsp312Asn polymorphism (p = 0.004) or Gln allele of XRCC1 Arg399Gln polymorphism with the Gln allele of XPD Lys751Gln polymorphism (p = 0.003) was highly significantly associated with the development of ESRD. This study revealed that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of ESRD. Furthermore, larger studies should be conducted to confirm these results.

Polymorphisms of DNA Repair Genes XPD (Lys751Gln) and XRCC1 (Arg399Gln), and The Risk of Age-Related Cataract: A Meta-Analysis

Purpose: A meta-analysis of available studies was used to test the association between two DNA repair genes and age-related cataract.Materials and Methods: A systematic search of the Chinese National Knowledge Infrastructure, EMBASE and PubMed databases identified six studies that were analyzed. Meta-analysis was used to evaluate single nucleotide polymorphisms (SNP) of the DNA repair gene xeroderma pigmentosum complementation group D (XPD) (Lys751Gln) and the X-ray repair cross-complementing gene 1 (XRCC1) (Arg399Gln). Only articles published before June 6, 2014, were included. The quality of the studies was determined using Newcastle–Ottawa Scale tools. The summary odds ratio (OR) and corresponding confidence interval (CI) for XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms and risk of age-related cataract were estimated by random and fixed-effects models. Sensitivity analysis was employed to determine the robustness of the conclusions.Results: Six studies, with a total of 1518 patients with cataractous lenses and 1437 subjects with clear lenses, were included in the meta-analysis. XRCC1 Arg399Gln polymorphisms were associated with cataract risk (recessive model: ORfixed = 0.79, 95% CI: 0.67–0.93; dominant model: ORfixed = 0.84, 95% CI: 0.64–1.11; additive model: ORfixed = 0.82, 95% CI: 0.72–0.92). Analysis of Chinese, but not non-Chinese subgroups, confirmed this association. The OR of XPD Lys751Gln polymorphisms for cataract was not significant. The associations remained significant after sensitivity analysis.Conclusions: This meta-analysis indicates that XRCC1 Arg399Gln polymorphisms, but not XPD Lys751Gln polymorphisms, are associated with risk of age-related cataract.

XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: A meta-analysis

The association between xeroderma pigmentosum complementation group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms and breast cancer risk has been widely reported, but the results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search strategy was conducted towards the electronic databases including Medline, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (Chinese). The association between the XPD polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of 22 studies with 18,136 cases and 18,351 controls were included in our meta-analysis. Among these, 12 studies with 7,667 cases and 7,480 controls for Asp312Asn polymorphism and 20 studies with 10,469 cases and 10,871 controls for Lys751Gln polymorphism. With regard to Asp312Asn polymorphism, no significantly associated was found with breast cancer risk. However, significant association was found between Lys751Gln polymorphism and breast cancer risk under all genetic models in overall populations (C vs. A—OR = 1.10, 95 % CI = 1.04–1.17, P = 0.002; CC vs. AA—OR = 1.17, 95 % CI = 1.06–1.30, P = 0.003; AC vs. AA—OR = 1.06, 95 % CI = 1.01–1.12, P = 0.032; CC vs. AC/AA—OR = 1.17, 95 % CI = 1.04–1.32, P = 0.009; CC/AC vs. AA—OR = 1.07, 95 % CI = 1.02–1.12, P = 0.005). In subgroup analysis base on ethnicity, significance was found in Caucasians and mix. The results suggest that XPD Asp312Asn polymorphism was not associated with breast cancer. The XPD Lys751Gln polymorphism significantly increased breast cancer risk, especially for Caucasian and mix.

DNA repair XRCC1 Arg399Gln polymorphism is associated with the risk of development of end-stage renal disease

Patients with end-stage renal disease (ESRD) display enhanced genomic damage. DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in patients with ESRD and to evaluate their association with ESRD development. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we genotyped four single nucleotide polymorphisms (SNPs) in XPD codons 312 and 751 and XRCC1 codons 194 and 399 in 136 dialysis patients (71 patients undergoing hemodialysis and 65 subjected to peritoneal dialysis) and 147 healthy controls. Patients having XRCC1 399 Arg/Gln (OR:1.98; 95% CI: 1.21-3.25, P = 0.007) or XRCC1-399 Gln/Gln (OR: 3.95; 95% CI: 1.45-10.76, P = 0.005) genotype had a significantly higher risk of ESRD than those with XRCC1 399 Arg/Arg genotype. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls, with OR = 2.03 (95% CI = 1.08-3.81, P = 0.03). We further investigated the potential combined effect of these DNA repair variants on the risk of ESRD development. It was found that combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with the two possible genotypes of XPD-Asp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. This is the first report showing an association between DNA repair gene polymorphisms and ESRD development, and suggests that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of the disease. Further larger studies should be conducted to confirm these results.

Analysis of XPD genetic polymorphisms of esophageal squamous cell carcinoma in a population of Yili Prefecture, in Xinjiang, China

To evaluate the association with genetic polymorphisms in Xeroderma pigmentosum complementation group D (XPD) gene of esophageal squamous cell carcinoma (ESCC) risk in a population of Yili Prefecture, in Xinjiang, China. A hospital-based case-control study was designed with 571 samples including 213 ESCC patients and 358 controls with age, gender and ethnicity-matched subjects (Kazakh, Uygur and Han ethnic). Genotypes were determined by PCR restriction fragment length polymorphism (PCR-RLFP) and confirmed by sequence. Relative risk associated with a particular genotype was estimated by calculating odds ratios (OR) along with 95% confidence intervals (CI). Significant ESCC risk was observed for XPD Lys751Gln (rs13181) frequency of presence C allele (OR: 1.409, 95% CI: 1.005-1.976) in the three ethnics. XPD Asp312Asn (rs1799793) of Han ethnic was associated with a borderline decrease of ESCC (OR: 0.362, 95% CI: 0.145-0.906), however, it was associated with ESCC risk in Uygur ethnic (OR: 2.403, 95% CI: 1.087-5.310). The results demonstrated an association between the XPD Lys751Gln (rs13181) for frequency of presence C allele and risk for ESCC in the three ethnics of Yili Prefecture, in Xinjiang, China. XPD Asp312Asn (rs1799793), which was associated with a borderline decrease of Han ethnic and risk of Uygur ethnic of ESCC, may play a different role in the three ethnics of ESCC.

Polymorphisms of the DNA Repair GenesXPDandXRCC1and the Risk of Age-Related Macular Degeneration

Oxidative stress seems to be an important factor in the development of age-related macular degeneration (AMD). The role of DNA repair mechanisms has also received attention recently in AMD pathogenesis. This case-control study was conducted to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD), codons 312 and 751, and x-ray cross-complementing group 1 (XRCC1), codons 194 and 399, in patients with AMD and in disease-free control subjects. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze XPD Asp312Asn and Lys751Gln and XRCC1 Arg194Trp and Arg399Gln in 120 patients with AMD (65 with dry type and 55 with wet type) and in age-matched 205 disease-free control subjects. Genotypic and allelic distributions of the polymorphisms were detected. For the XPD polymorphism, although the allele frequencies were not different between the patients and healthy control subjects, there was a significant difference between frequencies for the XPD751 Gln/Gln genotype in AMD patients (9%) and healthy control subjects (19%; P=0.02). The XPD751 Gln/Gln genotype seemed to have a protective effect against development of AMD (odds ratio, 0.41; 95% confidence interval, 0.19-0.88). Stratification by subtype of AMD revealed that the XPD751 Gln/Gln genotype was significantly lower only in the patients with dry type (P=0.02). These interactions remained nearly significant after Bonferroni correction (P<0.0125). Haplotype analysis for the two XPD polymorphisms revealed that the haplotype GC (312Asp-(751)Gln) was a protective haplotype against AMD. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the XRCC1 gene between the patients and the control subjects. Polymorphism in XPD codon 751 may be associated with the development of AMD.

XPD Lys751Gln polymorphism and breast cancer susceptibility: a meta-analysis involving 28,709 subjects

Published data on the association between Xeroderma Pigmentosum complementation group D (XPD) Lys751Gln polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 30 studies including 14,283 cases and 14,426 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with XPD 751Gln allele when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.13, 95% CI = 1.02-1.25; Gln/Gln vs. Lys/Lys: OR = 1.21, 95% CI = 1.06-1.38; dominant model: OR = 1.16, 95% CI = 1.05-1.29; and recessive model: OR = 1.14, 95% CI = 1.02-1.27). In the subgroup analysis by ethnicity, borderline significantly increased risks were found for Caucasians (Lys/Gln vs. Lys/Lys: OR = 1.09, 95% CI = 0.98-1.22; dominant model: OR = 1.10, 95% CI = 0.99-1.22) and significantly increased risks were found for Africans in dominant model (OR = 1.10, 95% CI = 1.04-1.15). When stratified by study design, statistically significantly elevated risk was found in population-based studies (Lys/Gln vs. Lys/Lys: OR = 1.10, 95% CI = 1.01-1.20; Gln/Gln vs. Lys/Lys: OR = 1.15, 95% CI = 1.01-1.31; dominant model: OR = 1.12, 95% CI = 1.03-1.23). In conclusion, this meta-analysis suggests that the XPD 751Gln allele is a low-penetrant risk factor for developing breast cancer.

XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk

BackgroundGenetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair.MethodsWe conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis.ResultsWe found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk.ConclusionThese findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.

DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute lymphoblastic leukemia

Polymorphisms have been identified in several DNA repair genes. These polymorphisms may effect DNA repair capacity and modulate cancer susceptibility. In this study, we aimed to determine the four polymorphisms in two DNA repair genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with childhood acute lymphoblastic leukemia (ALL), and evaluate their association with childhood ALL development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1 Arg194Trp, and XRCC1 Arg399Gln polymorphisms in 70 patients with childhood ALL and in 75 disease-free controls, who were of a similar age. No significant differences were observed among the study groups with regard to the XPD codon 312, XPD codon 751, XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However, the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with increased risk for ALL in females (OR = 5.47; 95% CI = 1.49–20.10; p = 0.008). This finding indicates that females carrying XRCC1 194Trp allele are at increased risk of developing childhood ALL. These results suggest that the risk of childhood ALL may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing childhood ALL, and also should be lead to improved treatment of ALL.

Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions

Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.

Polymorphisms in XPD Exons 10 and 23 and Bladder Cancer Risk

The nucleotide excision repair gene, xeroderma pigmentosum complementation group D (XPD), has been hypothesized to have a role in cancer risk, but results from prior molecular epidemiologic studies and genotype-phenotype analyses are conflicting. We examined the frequency of the XPD Asp312Asn polymorphism in exon 10 and the XPD Lys751Gln polymorphism in exon 23 in 505 incident bladder cancer cases and 486 healthy controls. Overall, the XPD exon 10 and 23 genotypes were not associated with bladder cancer risk, after adjusting for age, sex, ethnicity, and smoking status. A gender-specific role was evident that showed an increased risk for women, but not for men, associated with the variant genotypes for both exons. For example, when the exon 23 variant allele genotypes were combined (Lys/Gln + Gln/Gln), there was an increased bladder cancer risk in women [odds ratio (OR), 1.69; 95% confidence interval (95% CI), 1.12-2.58] but not in men (OR, 0.99; 95% CI, 0.79-1.24; P(interaction) = 0.041; OR, 1.62; 95% CI, 1.02-2.58). There was also a gene-smoking interaction that showed the variant alleles for either exon or the combination of both increase the risk of bladder cancer for light and heavy smokers. For exon 23 (P(interaction) = 0.057; OR, 1.21; 95% CI, 0.99-1.47), heavy smokers (> or = 20 pack-years) who carried the exon 23 variant allele genotypes had an OR of 4.13 (95% CI, 2.53-6.73), whereas heavy smokers with the wild-type genotypes were at lower risk (OR, 3.55; 95% CI, 2.19-5.75). Moderate smokers (1-19 pack-years) with the variant allele genotypes had an OR of 1.54 (95% CI, 0.94-2.53), whereas moderate smokers with the wild-type genotypes had an OR of 1.12 (95% CI, 0.63-1.98). Although we did not observe main effects associated with the XPD genotypes, these results do suggest the variant allele genotypes were associated with increased bladder cancer risk in women and smokers with statistically significant interactions in the exon 23 polymorphism. Although there is biological plausibility, these novel findings for gender and smoking should be interpreted with caution upon confirmation in larger studies.

XPD Lys751Gln Polymorphism and Etiology and Outcome of Childhood Acute Myeloid Leukemia.

Genetic polymorphism results in inter-individual variation in DNA repair capacity, and may in part account for susceptibility of a cell to genotoxic agents, and to malignancy. The DNA repair protein xeroderma pigmentosum complementation group D (XPD) is a major participant in the neucleotide excision repair pathway and is also involved in transcription initiation and in the control of cell cycle and apoptosis. Several studies have found associations between ineffective DNA repair and cancer risk. It is also thought that ineffective DNA repair may lead to additional genomic instability and tumors that are more aggressive. Several single nucleotide polymorphisms including an adenine to cytosine polymorphism leading to Lys751Gln in exon 23 of XPD have been shown to be associated with elevated frequency of chromosomal aberrations and variety of environmentally induced cancers in adults. We hypothesized that XPD polymorphism may play a role in causation of childhood AML. In addition, there are data that XPD polymorphism influences outcome of chemotherapy in adults with solid tumors. Therefore, we also evaluated its effect on outcome of AML therapy. Methods: 457 children treated for AML on CCG studies 2941 and 2961 (intensive induction with daunorubicin, idarubicin, Ara-C, 6-thioguanine, etoposide, dexamethasone, +/− fludarabine, Ara-C, idarubicin; consolidation with high-dose Ara-C and L-asparaginase or HLA-matched sibling BMT) were genotyped for XPD exon 23 polymorphism. Genotype frequencies were compared with published normal control frequencies. In addition, patient outcomes were analyzed according to genotype. Results: Comparison of gene frequencies in AML patients and reported normal controls showed similar frequencies (42.5% AA, 44.2% AC, 13.3% CC in patients vs. 44.2% AA, 45% AC, 10.8% CC in controls; p=0.54). There were no significant difference in OS (p=0.56), EFS (p=0.61), TRM (p=0.5) or relapse rate (p=0.88) between patients with 751AA genotype vs. 751AC/751CC genotypes, in contrast to reports in adult malignancies. Stratification of cases by age at diagnosis, white blood count at diagnosis, AML subtype, or cytogenetics revealed no difference in genotype frequencies. Conclusion: These data, representing the only data in pediatric AML, suggest that XPD genotype does not affect the etiology or outcome of childhood AML.