Browsing by Author "Guan, Xiaoxiang"
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Item Open Access Association between a rare novel TP53 variant (rs78378222) and melanoma, squamous cell carcinoma of head and neck and lung cancer susceptibility in non-Hispanic Whites.(Journal of cellular and molecular medicine, 2013-07) Guan, Xiaoxiang; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, QingyiRecently, several studies have investigated the association between a newly reported rare functional single nucleotide polymorphism (SNP) in TP53 (rs78378222) and cancer risk, but generated inconsistent findings. The present study further investigated this association with risk of melanoma, squamous cell carcinoma of head and neck (SCCHN) and lung cancer. Using volunteers of non-Hispanic Whites recruited for three large case-control studies, we genotyped the TP53 rs78378222 SNP in 1329 patients with melanoma, 1096 with SCCHN, 1013 with lung cancer and 3000 cancer-free controls. Overall, we did not observe any variant homozygotes in this study population, nor significant associations between the TP53 rs78378222AC genotype or C allele and risk for melanoma (P = 0.680 and 0.682 respectively) and lung cancer (P = 0.379 and 0.382 respectively), but a protection against SCCHN (P = 0.008 and 0.008 respectively), compared with the AA genotype or A allele. An additional meta-analysis including 19,423 cancer patients and 54,050 controls did not support such a risk association either. Our studies did not provide statistical evidence of an association between this rare TP53 variant and increased risk of melanoma, nor of lung cancer, but a possible protection against SCCHN.Item Open Access Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy.(BMC cancer, 2010-08-16) Guan, Xiaoxiang; Yin, Ming; Wei, Qingyi; Zhao, Hui; Liu, Zhensheng; Wang, Li-E; Yuan, Xianglin; O'Reilly, Michael S; Komaki, Ritsuko; Liao, ZhongxingVascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS).Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype.Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.Item Open Access Polymorphisms of TGFB1 and VEGF genes and survival of patients with gastric cancer.(Journal of experimental & clinical cancer research : CR, 2009-06-30) Guan, Xiaoxiang; Zhao, Hui; Niu, Jiangong; Tan, Dongfeng; Ajani, Jaffer A; Wei, QingyiSome TGFB1 and VEGF polymorphisms are believed to be functional. Given that these genes are involved in tumor growth and progression including angiogenesis, dissemination, and invasiveness, we hypothesized that these polymorphisms would be associated with survival in patients with gastric cancer.We genotyped TGFB1 -509 C>T, +1869 T>C, and +915 G>C and VEGF -1498T>C, -634G>C, and +936C>T in 167 patients with gastric cancer. Using the Kaplan and Meier method, log-rank tests, and Cox proportional hazard models, we evaluated associations among TGFB1 and VEGF variants with overall, 1-year, and 2-year survival rates.Although there were no significant differences in overall survival rates among all polymorphisms tested, patients with TGFB1+915CG and CC genotypes had a poorer 2-year survival (adjusted hazard ratio (HR), 3.06; 95% confidence interval (CI), 1.09-8.62; P = 0.034) than patients with the GG genotype had. In addition, patients heterozygous for VEGF -634CG also had a poorer 1-year survival (adjusted HR, 2.08; 95% CI, 1.03-4.22; P = 0.042) than patients with the -634GG genotype.Our study suggested that TGFB1+915CG/CC and VEGF -634CG genotypes may be associated with short-term survival in gastric cancer patients. However, larger studies are needed to verify these findings.Item Open Access The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer.(BMC gastroenterology, 2009-10-16) Guan, Xiaoxiang; Zhao, Hui; Niu, Jiangong; Tang, Dongfeng; Ajani, Jaffer A; Wei, QingyiBoth TGF-beta1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the TGFB1 and VEGF genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population.The risk associated with genotypes and haplotypes of four TGFB1 SNPs and four VEGF SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity.Compared with the VEGF-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other TGFB1 and VEGF SNPs was associated with risk of gastric cancer.Our data suggested that the VEGF-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.Item Open Access TNFRSF1B +676 T>G polymorphism predicts survival of non-small cell lung cancer patients treated with chemoradiotherapy.(BMC cancer, 2011-10-14) Guan, Xiaoxiang; Liao, Zhongxin; Ma, Hongxia; Qian, Ji; Liu, Zhensheng; Yuan, Xianglin; Gomez, Daniel; Komaki, Ritsuko; Wang, Li-E; Wei, QingyiThe dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy.We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629) and -1031 T>C (rs1799964); TNFRSF1B +676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N2-3 vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T3-4 vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03).Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.