No abstract

Oxidative DNA damage caused by reactive oxygen species can produce 8-oxoguanine (8-oxoG) in DNA, which is misread and leads to G:C fi T:A transversions. This can be carcinogenic. Repair of 8-oxoG by the base excision repair pathway involves the activity of human 8-oxoG DNA glycosylase 1 (hOGG1). Accumulating evidence suggests that the hOGG1 Ser326Cys polymorphism affects the activity of hOGG1 and might serve as a genetic marker for susceptibility to several cancers. To determine whether this polymorphism is associated with risk of childhood acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped the hOGG1 Ser326Cys polymorphism (rs1052133) in a case-control study including 415 cases and 511 controls. We found that there was a significant difference in the genotype distributions of the hOGG1 Ser326Cys polymorphism between cases and controls (P = 0.046), and the combined genotypes Ser/Ser and Ser/Cys were associated with a statistically significantly decreased risk of ALL (adjusted odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.49-0.88, P = 0.005). Furthermore, we found a decreased risk for high risk ALL (adjusted OR = 0.60, 95% CI = 0.40-0.88, P = 0.005), low risk ALL (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.042), and Bphenotype ALL (adjusted OR = 0.63, 95% CI = 0.46-0.86, P = 0.003) among children with the Ser/Ser and Ser/Cys genotypes. Our results suggest that the hOGG1 Ser326Cys polymorphism is associated with susceptibility to childhood ALL in a Chinese population. (Cancer Sci 2011; 102: 1123-1127 A cute lymphoblastic leukemia (ALL) is a clonal disease of a lymphoblast and is the most frequent malignancy in children younger than 15 years, accounting for approximately 25% of all pediatric malignancies.(1) Studies of developed countries report that cancer incidence among children has risen steadily since the 1950s, with 38 new cases per million occurring every year.(2) Like other cancers, childhood ALL is generally believed to be caused by a combination of genetic susceptibility factors and environmental exposures. DNA damage to hematopoietic precursor cells is essential for the development of leukemia, (4,5) which occurs at an estimated rate of 10 000 lesions per cell per day.(6) Correspondingly, several DNA repair pathways have evolved to maintain the genetic integrity of cells and prevent carcinogenesis, including base excision repair (BER), (7)(8)(9) mismatch repair, and nucleotide excision repair. The DNA lesion 8-oxoguanine (8-oxoG), produced by reactive oxygen species, is one of the most common forms of oxidative damage to DNA, and leads to G:C fi T:A transversions, causing carcinogenesis.(10,11) Human 8-oxoG DNA glycosylase 1 (hOGG1) is a key enzyme in the BER pathway and repairs 8-oxoG. (7,12) Many functional and epidemiological studies have suggested that the Ser326Cys polymorphism in exon 7 of the hOGG1 gene might affect the activity of the enzyme, (13,14) and therefore may serve as a genetic marker for susceptibility to various cancers. (15)(16)(17)(18) Additionally, a r...

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3′UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR  =  1.84, 95% CI  =  1.14 —2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR  = 1.95, 95% CI  =  1.04–3.67), low-risk ALL (adjusted OR  =  2.09, 95% CI  =  1.13–3.87), B-phenotype ALL patients (adjusted OR  =  1.78, 95% CI  =  1.08–2.95) and T-phenotype ALL patients (adjusted OR  =  2.87, 95% CI  =  1.16–7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.