Association of <i>p53</i> codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck

Li, Fanglin; Chen, Xingming; Zafereo, Mark; Wei, Qingyi; Li, Guojun

doi:10.1002/cncr.25072

Cited by 16 publications

(35 citation statements)

References 39 publications

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“…On the other hand “CC” genotype with PNI was found to decrease HR for TC. Increased HRs for HNSCC patients have also been reported earlier with “GC” and “CC” genotypes . Analysis of our data suggests differential impact of the intronic polymorphisms on the HRs of BMC and TC patients.…”

Section: Discussionsupporting

confidence: 85%

Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40‐41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients

Nagam

Katta

Prasad

2016

Molecular Carcinogenesis

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Reports on the association of TP53 polymorphisms with oral cancer are not only limited but also not specific to site and/or gender. Hence, we examined the effect of TP53 polymorphisms (EX4 215G>C, IVS3+40-41ins16 and IVS6+62G>A) on buccal mucosa cancer (BMC) and tongue cancer (TC) risk, survival of patients in relation to risk and clinical factors, gender wise (excepting for estimating hazards ratio [HR]), using Fisher's Exact Test, Kaplan-Meier analysis, and Cox-proportional hazards models. The exonic polymorphism increased BMC and TC risk in males by 2-4-fold. The IVS3+40-41ins16 was protective against BMC and TC in both genders, whereas IVS6+62G>A protected only males against TC. Genotype combinations and haplotypes which altered the risk of cancers in males and females were different. TC males, aged 40-44 years and females, aged 55-59 years survived better than BMC patients. The IVS3+40-41ins16 polymorphism differentially impacted survival of female patients exposed to tobacco. TC patients with EX4 215GC with lymphovascular spread (LVS) and metastasis exhibited higher HR while, patients with EX4 215CC and perineural invasion (PNI) showed lower HR. Impact of the intronic variants along with clinical parameters on survival and HR estimates varied between BMC and TC. Our bioinformatics analysis revealed the presence of CTCF binding site within TP53 gene. In conclusion, the polymorphisms altered risk and survival of BMC and TC in a gender specific manner, which varied with mode of tobacco and/or alcohol use. The current study, therefore underscores strong need for research, stratified by tumor site and gender. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 85%

Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40‐41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients

Nagam

Katta

Prasad

2016

Molecular Carcinogenesis

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“…The methods for the genotyping have been previously described [29], [30]. Approximately 10% of the samples were also selected for retesting for quality control purposes, and the repeated results were 100% concordant.…”

Section: Methodsmentioning

confidence: 99%

Association of Combined p73 and p53 Genetic Variants with Tumor HPV16-Positive Oropharyngeal Cancer

et al. 2012

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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.

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“…There is also an individual susceptibility to cancer even with the same environmental exposure (49,50). These differences may be affected by variants of genes in the tumor genesis.…”

Section: Discussionmentioning

confidence: 99%

Lack of Association between Cytotoxic T-Lymphocyte Antigen-4 −318C/T Polymorphism and Cancer Risk: A Meta-Analysis of Case-Control Studies

Xia

Shi

Wen-ling

et al. 2013

Technol Cancer Res Treat

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results. We performed a meta-analysis to examine the association between CTLA-4 -318C/T polymorphisms and cancer susceptibility. Eligible studies were identified by searching several databases for relevant reports published up to September 30, 2012. Sixteen eligible studies with a total of 6190 patients and 6560 controls were included to summarize the association between CTLA-4 -318C/T polymorphisms and the risk of cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.Overall, no significant associations were found in all genetic models when all studies were pooled into the meta-analysis (for -318C/T polymorphisms as estimated using a fixed effect

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Association of p53 codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck

Cited by 16 publications

References 39 publications

Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40‐41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients

Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40‐41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients

Association of Combined p73 and p53 Genetic Variants with Tumor HPV16-Positive Oropharyngeal Cancer

Lack of Association between Cytotoxic T-Lymphocyte Antigen-4 −318C/T Polymorphism and Cancer Risk: A Meta-Analysis of Case-Control Studies

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