Browsing by Author "Zhang, Fenghua"

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
    (Int J Cancer, 2015-11-15) Zhang, Fenghua; Sturgis, Erich M; Sun, Yan; Zhang, Yang; Wei, Qingyi; Zhang, Caiyun; Zheng, Hongliang; Li, Guojun
    Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.
  • Thumbnail Image
    ItemOpen Access
    Association of combined p73 and p53 genetic variants with tumor HPV16-positive oropharyngeal cancer.
    (PloS one, 2012-01) Wang, Zhongqiu; Sturgis, Erich M; Guo, Wei; Song, Xicheng; Zhang, Fenghua; Xu, Li; Wei, Qingyi; Li, Guojun
    p53 and p73 interact with human papillomavirus (HPV) E6 and E7 oncoproteins. The interplay between p53 and p73 and HPV16 may lead to deregulation of cell cycle and apoptosis, through which inflammation/immune responses control the HPV clearance and escape of immune surveillance, and subsequently contribute to tumor HPV16 status. In this case-case comparison study, HPV16 status in tumor specimens was analyzed and p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms were genotyped using genomic DNA from blood of 309 oropharyngeal cancer patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in univariate and multivariable logistic regression models to examine the association. The results from this study showed both p53 variant genotypes (Arg/Pro+Pro/Pro) and p73 variant genotypes (GC/AT+AT/AT) were significantly associated with HPV16-positive tumor in oropharyngeal cancer patients (OR, 1.9, 95% CI, 1.1-3.3 and OR, 2.1, 95% CI, 1.2-3.8, respectively), while the combined variant genotypes (p53 Pro carriers and p73 AT carriers) exhibited a significantly greater association with HPV16-positive tumor (OR, 3.2, 95% CI, 1.4-7.4), compared with combined wild-type genotypes (p53 Arg/Arg and p73 GC/GC), and the association was in a statistically significant dose-effect relationship (p = 0.001). Moreover, such association was more pronounced among several subgroups. These findings suggest that variant genotypes of p53 and p73 genes may be individually, or more likely jointly, associated with tumor HPV16-positive oropharyngeal cancer patients, particularly in never smokers. Identification of such susceptible biomarkers would greatly influence on individualized treatment for an improved prognosis.
  • Thumbnail Image
    ItemOpen Access
    Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck.
    (Molecular cancer, 2012-03-26) Wang, Zhongqiu; Sturgis, Erich M; Zhang, Fenghua; Lei, Dapeng; Liu, Zhensheng; Xu, Li; Song, Xicheng; Wei, Qingyi; Li, Guojun
    Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (Ptrend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.