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

Xu, Jiali; Hu, Lingmin; Huang, Ming‐De; Zhao, Wei; Yin, Yongmei; Hu, Zhibin; Ma, Hongxia; Shen, Hongbing; Shu, Yongqian

doi:10.7314/apjcp.2012.13.3.851

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…Our study further elucidates the relationship between NBS1 SNPs and mortality. One recent pilot study reported an improved progression-free survival with minor C allele of NBS1 rs1805794 (SNP in a complete LD with NBS1 rs1061302 in our study) among 147 Chinese patients with inoperable NSCLC who received platinum-based chemotherapy [55]. Our study suggests an increased hazard of overall death among NSCLC patients carrying the minor G allele of rs1061302.…”

Section: Discussionsupporting

confidence: 59%

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

Yang

Chang

Park

et al. 2013

Cancer Causes Control

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Purpose Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown. Methods Using follow-up data from 611 lung-cancer cases and 601 UADT-cancer cases from a population-based case-control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) for main effects and ratios of hazard ratios (RHR) derived from product terms to assess hazard-ratio variations by each SNP. Bayesian methods were used to account for multiple comparisons. Results We observed 406 (66%) deaths in lung-cancer cases and 247 (41%) deaths in UADT-cancer cases with median survival of 1.43 and 1.72 years, respectively. Ever tobacco smoking was positively associated with mortality for both cancers. We observed an upward dose-response association between smoking pack-years and mortality in UADT squamous cell carcinoma. The adjusted HR relating smoking to mortality in non-small cell lung cancer (NSCLC) was greater for cases with the GG genotype of NBS1 rs1061302 than for cases with AA/AG genotypes (semi-Bayes adjusted RHR = 1.97; 95% limits = 1.14, 3.41). Conclusions A history of tobacco smoking at cancer diagnosis was associated with mortality among patients with lung cancer or UADT squamous cell carcinoma. The HR relating smoking to mortality appeared to vary with the NBS1 rs1061302 genotype among NSCLC cases.

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Section: Discussionsupporting

confidence: 59%

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

Yang

Chang

Park

et al. 2013

Cancer Causes Control

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“…The genomic DNA of each subject was extracted by a routine method [38]. TaqMan allelic discrimination assay was chosen for genotyping using an ABI 7900 system (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Genetic Variation in a MicroRNA-502 Minding Site in SET8 Gene Confers Clinical Outcome of Non-Small Cell Lung Cancer in a Chinese Population

Yin

Gao

et al. 2013

PLoS ONE

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BackgroundGenetic variants may influence microRNA-target interaction through modulate their binding affinity, creating or destroying miRNA-binding sites. SET8, a member of the SET domain-containing methyltransferase, has been implicated in a variety array of biological processes.MethodsUsing Taqman assay, we genotyped a polymorphism rs16917496 T>C within the miR-502 binding site in the 3′-untranslated region of the SET8 gene in 576 non-small cell lung cancer (NSCLC) patients. Functions of rs16917496 were investigated using luciferase activity assay and validated by immunostaining.ResultsLog-rank test and cox regression indicated that the CC genotype was associated with a longer survival and a reduced risk of death for NSCLC [58.0 vs. 41.0 months, P = 0.031; hazard ratio = 0.44, 95% confidential interval: 0.26–0.74]. Further stepwise regression analysis suggested rs16917496 was an independently favorable factor for prognosis and the protective effect more prominent in never smokers, patients without diabetes and patients who received chemotherapy. A significant interaction was observed between rs16917496 and smoking status in relation to NSCLC survival (P<0.001). Luciferase activity assay showed a lower expression level for C allele as compared with T allele, and the miR-502 had an effect on modulation of SET8 gene in vitro. The CC genotype was associated with reduced SET8 protein expression based on immunostaining of 192 NSCLC tissue sample (P = 0.007). Lower levels of SET8 were associated with a non-significantly longer survival (55.0 vs. 43.1 months).ConclusionOur data suggested that the rs16917496 T>C located at miR-502 binding site contributes to NSCLC survival by altering SET8 expression through modulating miRNA-target interaction.

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“…The protein encoded by NBN gene is an important component of the system repairing DNA double-strand breaks that can be induced by different environmental and endogenous agents, including cisplatin. The existing data suggest connections between polymorphic variants of the NBN gene and the results of cisplatin-based chemotherapy [67].…”

Section: Resultsmentioning

confidence: 99%

Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

Khrunin¹,

Moisseev²,

Gorbunova³

et al. 2018

Ovarian Cancer - From Pathogenesis to Treatment

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There is substantial interindividual variability in the efficacy and tolerability of anticancer drugs. Such differences can be greater between individuals of different ethnicities. The clinical studies demonstrate that individuals from Asia (East Asia) are more susceptible to the effects of platinum-containing chemotherapies than their Western counterparts. To determine whether population-related genomics (i.e., frequencies of DNA polymorphisms) contribute to differences in patient outcomes, polymorphisms in 109 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis were tested in Russian (Caucasians) and Yakut (North Asians) ovarian cancer patients receiving cisplatin-based chemotherapy. Totally, 232 polymorphisms were genotyped in individual DNA samples using conventional PCR and arrayed primer extension technology. Single nucleotide polymorphisms (SNPs) in more than 30 genes were found to be associated with one or more of clinical end points (i.e., tumor response, progression-free survival, overall survival, and side effects). However, all associations between SNPs and clinical outcomes were specific for each of ethnic group studied. These findings let us to propose the existence of distinctive ethnic-related characteristics in molecular mechanisms determining the sensitivity of patients to platinum drug effects.

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

Cited by 16 publications

References 43 publications

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

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

Genetic Variation in a MicroRNA-502 Minding Site in SET8 Gene Confers Clinical Outcome of Non-Small Cell Lung Cancer in a Chinese Population

Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

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