hOGG1 Ser326Cys polymorphism and risk of childhood acute lymphoblastic leukemia in a Chinese population

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...

The minus of a plus is a minus. Mass death of selected neuron populations in sporadic late-onset neurodegenerative disease may be due to a combination of subtly decreased capacity to repair oxidative DNA damage and increased propensity for damage-related apoptosis

“…This may be another example of the inverse relationship between age-dependent degenerative disease and cancer, brought about by a lifelong compromise between accuracy of identification and repair of damage and the propensity to route damaged cells to apoptosis. Interestingly, children carriers of Cys/Cys genotypes by the Ser326Cys polymorphism of hOGG1 were identified to be at increased risk of development of ALL than carriers of at least one Ser allele, [131] supporting the hypothesis that the risk of LONDD was associated with decreased risk of most cancers except for those that originated from cells with differentiation blocks (as is ALL).…”

Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patients

“…In particular, associations with the Ser326Cys polymorphism have been reported for different cancers, such as smoking-associated lung cancer, gall-bladder cancer and lymphoblastic leukemia [16][17][18]; however, a meta-analysis suggested that the variant 326Cys allele would play a significant protective effect against breast cancer in European women [19]. In a recent study by our group we have not found associations between this SNP and DTC incidence [20].…”

Individual capacity for detoxification of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair

“…were iden fied to be at decreased risk for development of acute childhood lymphoblas c leukemia [130]. Carriership of polymorphisms in BER genes is associated with suscep bility to Grave's disease, a toxic hyperfunc on of the thyroid gland that affects virtually all organs and systems.…”