Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China

Lan, Qing; Shen, Min; Berndt, Sonja I.; Bonner, Matthew R.; He, Xingzhou; Yeager, Meredith; Welch, Robert; Keohavong, Phouthone; Donahue, Mark; Hainaut, Pierre; Chanock, Stephen J.

doi:10.1016/j.lungcan.2005.04.004

Cited by 41 publications

(21 citation statements)

References 24 publications

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“…However, a recent study found no association between this variation and breast cancer risk in a European population (Kuschel et al, 2002). Interestingly, the rs1805794 GG genotype was demonstrated to be associated with risk of lung cancer instead of the GC or CC genotype in a Chinese study (Lan et al, 2005). Our present study also supported that NBS1 rs1805794 C/G variant genotypes are related to increased risk of HCC.…”

Section: Discussionsupporting

confidence: 76%

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

Huang

Chen

et al. 2012

DNA and Cell Biology

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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.

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Section: Discussionsupporting

confidence: 76%

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

Huang

Chen

et al. 2012

DNA and Cell Biology

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“…The genes included in the prediction model have biological plausibility. Two of the five genes whose sequence variation is associated with methylation, NBN and XRCC3, have shown association with lung cancer (18,27). SNPs within the DNA-PKc and CHEK2 genes have been associated with breast and other cancers, whereas no studies have been conducted with MRE11A (19,28).…”

Section: Resultsmentioning

confidence: 99%

“…In assigning a prior probability for these genes, we considered the strong association between DSBRC and risk for promoter methylation and the stringent r 2 value (0.8) for selecting tag SNPs. Based on the evidence for associations between SNPs in CHEK2, XRCC3, DNA-PKc, NBN, LIG4, and XRCC2 and several cancers (18)(19)(20)(21)(22)(23)(24)(25), we assigned a relatively high prior probability range (0.1-0.25) for SNPs of these six genes. In contrast, for MRE11A, Ku80, RAD50, and CHEK1, a relatively low prior probability range (0.01-0.1) was assigned because there are no studies that have addressed the association of variants within these genes to cancer.…”

Section: Cancer Researchmentioning

confidence: 99%

Double-Strand Break Damage and Associated DNA Repair Genes Predispose Smokers to Gene Methylation

et al. 2008

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Gene promoter hypermethylation in sputum is a promising biomarker for predicting lung cancer. Identifying factors that predispose smokers to methylation of multiple gene promoters in the lung could affect strategies for early detection and chemoprevention. This study evaluated the hypothesis that double-strand break (DSB) repair capacity and sequence variation in genes in this pathway are associated with a high methylation index in a cohort of current and former cancerfree smokers. A 50% reduction in the mean level of DSB repair capacity was seen in lymphocytes from smokers with a high methylation index, defined as three or more of eight genes methylated in sputum, compared with smokers with no genes methylated. The classification accuracy for predicting risk for methylation was 88%. Single nucleotide polymorphisms within the MRE11A, CHEK2, XRCC3, DNA-PKc, and NBN DNA repair genes were highly associated with the methylation index. A 14.5-fold increased odds for high methylation was seen for persons with seven or more risk alleles of these genes. Promoter activity of the MRE11A gene that plays a critical role in recognition of DNA damage and activation of ataxiatelangiectasia mutated was reduced in persons with the risk allele. Collectively, ours is the first population-based study to identify DSB DNA repair capacity and specific genes within this pathway as critical determinants for gene methylation in sputum, which is, in turn, associated with elevated risk for lung cancer. [Cancer Res 2008;68(8):3049-56]

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“…Publications on NBS1 polymorphisms have mainly focused on rs1805794 and the risk of cancers including lung, breast, bladder, renal cell cancers, non-Hodgkin lymphoma and childhood acute leukemia (Medina et al, 2003;Lan et al, 2005;Zienolddiny, 2005;Landi et al, 2006;Ryk et al, 2006;Hsu et al, 2007;Choudhury et al, 2008;Margulis et al, 2008;Mosor et al, 2008;Schuetz et al, 2009;Stern et al, 2009;Park et al, 2010), but the results were not consistent. A recent meta-analysis on rs1805794 has shed light on a positive association between the variant genotype of rs1805794 and the risk of multiple cancers (MeiXia et al, 2009).…”

Section: 851 Variants Of Nbs1 Predict Clinical Outcome Of Chemotheramentioning

confidence: 99%

“…Rs1805794 located in exon 5 of NBS1 is one of the most common polymorphisms and can induce an amino acid substitution from Glu to Gln. Studies have investigated the association between rs1805794 and risk of multiple cancers, such as lung, breast, bladder and nasopharyngeal carcinoma (Medina et al, 2003;Lan et al, 2005;Lu et al, 2006;Hsu et al, 2007;Stern et al, 2009;Zheng et al, 2011). However, only one study has explored the effect of this polymorphism on prognosis of human cancer and reported that it was not associated with the survival of esophagus or gastric adenocarcinoma after platinum-based neoadjuvant poly-chemotherapy (Ott et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Hu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China

Cited by 41 publications

References 24 publications

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

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

Double-Strand Break Damage and Associated DNA Repair Genes Predispose Smokers to Gene Methylation

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

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