p53 Arg72Pro Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis

Abstract

Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of p53 Arg72Pro polymorphism binds more ardently with HPV E6 than the Pro variant. Here we evaluate the role of p53 Arg72Pro polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 Arg allele [OR 1.37; 95% confidence intervals (CI), 1.15-1.62; P < 0.001]. This association was not seen in HPVnegative individuals. p53 Arg72Pro was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The Arg variant of p53 Arg72Pro is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPVnegative patients.

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence

“…Consistent with our results, Hu et al21 also reported that the TP53 G72 (Arg) was significantly overtransmitted in Caucasian CxCa subjects of a family‐based association study where HPV was determined, especially in subjects who were infected with HPV16/18 21. In validation of our results, a systematic meta‐analysis including 49 studies showed that HPV‐positive patients had significantly elevated odds of progression from squamous intraepithelial lesions to invasive CxCa when associated with the p53 Arg allele (OR, 1.37; 95% CI, 1.15‐1.62; P  < .001) that was not seen in HPV‐negative individuals 25. The authors further stated that the Arg allele of p53 codon 72 is associated with the progression from squamous intraepithelial lesions to CxCa in the presence of HPV positivity only.…”

Expression of the receptor for advanced glycation end-products and frequency of polymorphism in lung cancer

“…A number of studies have focused on the molecular and cellular changes that occur during the initiation and progression of lung cancer. However, the gene polymorphisms involved, which are closely associated with the tumorigenesis and invasion of lung cancer, remain unclear (2)(3)(4). Therefore, it is essential to investigate effective lung cancer biomarkers at the early stages of disease and identify novel targets for the treatment of the disease.…”

Detection of human papillomavirus and expression of osteopontin in cervical cancer specimens

“…The process of invasion and metastasis of tumor cells is complex, including a series of interactions amongst tumor cells and between tumor cells, host cells and extracellular matrixes. In particular, the involvement of multiple cytokines in cell regulation allows for metastasis and rapid growth of tumor cells (24,25). OPN is one such cytokine, and functions as a secretory multi-functional phosphorylated sialoglycoprotein and a non-collagenic adhesion molecule in the extracellular matrix (26).…”