Genetic Variation in the NBS1 Gene Is Associated with Hepatic Cancer Risk in a Chinese Population

Abstract

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3¢UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR] = 1.41; 95% confidence interval [CI] = 1.11-1.80), the CC carriers had a further increased risk of HCC (OR = 2.27; 95% CI = 1.68-3.14), and there was a trend for an allele dose effect on risk of HCC ( p < 0.001). Also, we found that the risk effect of rs1805794 CC + CG was more pronounced in HCC patients that drank (OR = 2.28, 95% CI = 1.55-3.29 for drinkers; OR = 1.31, 95% CI = 1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.

Identification of a novel HRAS variant and its association with papillary thyroid carcinoma

“…Furthermore, the identification of novel variants often requires DNA sequencing, which is an expensive technology with limited availability in certain countries. The most commonly used method is SSCP (26,27), which is an efficient and sensitive technique used for the identification of single-base mutations.…”

Hepatitis B virus pre‐S2 mutant large surface protein inhibits DNA double‐strand break repair and leads to genome instability in hepatocarcinogenesis

“…NBS1, as a key regulator of the MRN complex essential for the sensing and early processing of DNA DSB via its DNA-binding and nuclease activities, is important in DNA DSB repair [20]. Interestingly, loss of NBS1 activity has been reported in HCC [29], which indicates a strong correlation between the loss of NBS1 activity and hepatocarcinogenesis. In addition, defects in the nuclear translocation of some other importin α1 cargos, such as p27 Kip1 , p53, galectin-3 and heat-shock protein 90, have been associated with HCC [30], supporting the role of importin α1 function in anti-carcinogenesis.…”

Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation

“…Associations between NBS1 polymorphisms with cancer susceptibility have been widely studied, in particular NBS1 rs1805794 (E184Q) -- a 3′-UTR polymorphism in a complete LD (r 2 = 1) with rs1061302 (exon 13, P672P) in our study. The susceptibility of lung [9–11], head and neck [10, 12], prostate [47], breast [48–50], bladder [10, 51, 52], leukemia [53], and liver cancers [10, 54] has been shown to be associated with NBS1 rs1805794 or rs1061302. Our study further elucidates the relationship between NBS1 SNPs and mortality.…”