NBS1 rs1805794G>C polymorphism is associated with decreased risk of acute myeloid leukemia in a Chinese population

Abstract

As a key encoding protein gene of MRN (MRE11-RAD50-NBS1) complex, NBS1 plays a crucial role in maintaining genomic stability and preventing cell apoptosis, inflammation and tumorgenesis. Single nucleotide polymorphisms (rs2735383 and rs1805794) in NBS1 have been frequently studied in some cancers with discordant results in previous case-control studies. However, the relationship between these two functional polymorphisms and the susceptibility to acute myeloid leukemia (AML) in Chinese population has not been investigated. We performed a case-control study with 428 patients and 600 controls to detect the association between the two polymorphisms of NBS1 and the risk of AML in a Chinese population. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was carried out to determine the genotypes of potential functional SNPs in NBS1 gene. The results showed that compared with the homozygous carriers rs1805794CC, rs1805794GC genotype was significantly associated with decreased risk of AML in total subjects (adjusted odds ratio (OR) = 0.50; 95% CI = 0.37-0.67), the risk decreased even further in those carrying rs1805794GG genotype (OR = 0.23; 95% CI = 0.16-0.34). No significant association was found between rs2735383C>G polymorphism and the risk of AML (OR = 0.93; 95% CI = 0.71-1.22 for GC; OR = 0.78; 95% CI = 0.53-1.13 for CC, P = 0.152). These findings indicated that rs1805794G/C polymorphism in NBS1 may play a protective role in mediating the risk of AML.

Homologous Recombination Repair Polymorphisms, Cancer Susceptibility and Treatment Outcome

“…Interestingly, in one meta-analysis decreased risk was observed for cancers of digestive system [43]. Decreased risk was also reported in some studies in rare cancer types such as acute myeloid leukemia [45] or osteosarcoma [46]. The observed discrepancies could be due to large heterogeneity between studies.…”

NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review

“…In another Chinese hospital-based case-control study, the association between the rs1805794 and rs2735383 (located at the 3’-UTR of NBN ) polymorphisms and acute myeloid leukemia (AML) risk was investigated in 428 ethnically homogeneous AML patients and 600 cancer-free controls [149]. Genotypes were distributed in accordance with Hardy-Weinberg equilibrium.…”

“…Overall, it was found that for the rs1805794 variant the genotypes GC+GG appeared to be protective against AML, and that the risk decreased as the number of G alleles increased. On the contrary, the 3’- UTR NBN polymorphism was not associated with AML [149]. …”

An Approach to Elucidate NBS1 Function in DNA Repair Using Frequent Nonsynonymous Polymorphism in Wild Medaka (Oryzias latipes) Populations

“…Q185E is a widely prevailed polymorphism in human (e. g. Q185 allele frequency is 44.7% in Tokyo) [9,10]. A variety of previous studies reported that Q185 allele is associated with higher cancer risks, such as bladder cancer in Swedish people [11] and acute myeloid leukemia in Chinese [12], suggesting that the mutation to glutamic acid at Q185 residue in hNBS1 has some biological significance. Nonetheless, it remains unclear how a mutation at Q185 residue impacts the molecular function of NBS1 and DSB repair.…”