HPV, KRAS mutations, alcohol consumption and tobacco smoking effects on esophageal squamous-cell carcinoma carcinogenesis

Abstract

Esophageal squamous-cell carcinoma (ESCC) is an invasive neoplastic disease generally associated with poor survival rates. The incidence of ESCC is characterized by marked geographic variation, with highest rates noted in developing Southeastern African, Central and Eastern Asian countries. In the developed Western European and North American regions where there is a low disease incidence, heavy alcohol and cigarette consumption constitute major risk factors. The toxic effects of both these risk factors cause chronic irritation and inflammation of the esophageal mucosa, while at the cellular level they further confer mutagenic effects by the activation of oncogenes (e.g., RAS mutations), inhibition of tumor-suppressor genes, and profound DNA damage. Viral infections, particularly with human papillomavirus, may activate specific antiapoptotic, proliferative and malignant cellular responses that may be intensified in combination with the effects of alcohol and tobacco. In countries with a high ESCC incidence, low socioeconomic status and an inadequate diet of poorly preserved food are combined with basic nutritional deficiencies and inadequate medical treatment. These conditions are favorable to the above-mentioned risk factors implicated in ESCC development, which may be present and/or habitually used in certain populations. New perspectives in epidemiological studies of ESCC development and its risk factors allow genome-wide research involving specific environments and habits. Such research should consist of adequately large and representative samples, should use newly designed informative genetic markers, and apply genomic variation analysis of the functional transcripts involved in malignant cell cycle regulation and neoplastic transformation in the multi-step process of ESCC carcinogenesis.

Detection of Human Papilloma Virus Type 16 in Epithelial Ovarian Tumors Samples

“…In recent years, it has been reported that the rate of OCa from 192,000 in 2005 has increased to 20,000 in 2008 (13,14). Therefore, the presence of HPV infection in the epithelial cell of the ovarian carcinoma has been a marvelous subject (15). Anal, oropharyngeal, penile, vulvar, and HPV-related tumors, represent a further 0.7% of the entire carcinoma regions in both genera (women and men), so that HPV is said to be accountable for 5.2% of the entire carcinoma worldwide (6,16).…”

A Perspective on Chemoprevention by Resveratrol in Head and Neck Squamous Cell Carcinoma

“…Both of these enzymes are known to promote DNA synthesis, cell proliferation, invasion, and metastasis [ 27 ]. In this context, resveratrol is known to inhibit de novo synthesis of iNOS and COX2 via inhibition of NF-kB pathway as well the upstream kinases activating this pathway [ 51 ]. Resveratrol also targets nitric oxide production and lipoxygenase-stimulated infl ammatory responses [ 7 ].…”

“…Similarly, alcohol has been reported to either directly interacting with cell membrane proteins or modulating cellular function [ 57 ]. Long-term alcohol exposure preferentially causes K -ras mutation, impairs p16INK4A protein expression, and induces mutation in both retinoblastoma (Rb) and p53 proteins thereby, triggering cancer promotion [ 51 ]. Aberration of all these genes promote cell survival, evade apoptosis, and stimulate cell proliferation of cancer cells [ 49 ].…”

“…This has been supported by the studies reporting that alcoholics have reduced levels of zinc, iron, vitamin E, and vitamin B [ 17 , 57 ]. Once nutrients are absorbed, alcohol can prevent their utilization in the body by altering their transport, storage, and excretion [ 51 ].…”

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“…Based on their association with cervical cancer, HPV types are classified as high-risk 18, 31, 33, 35,39,45,51,52,56,58,59,68, 30, 34,53,66,67,69,70,73,82,85) [2]. Evidence of the potential role of HPV in other tumor types has been shown, as well [3][4][5][6][7][8]. High-risk HPV types contribute significantly to viral associated neoplasms, accounting for approximately 600,000 cases (5%) of cancers worldwide annually [9].…”