Cigarette: releases polycyclic aromatic hydrocarbons which are broken down by aryl hydrocarbon hydroxylase to produce carcinogenic epoxide. These binds to DNA and causes supression of P53 tumour supressor gene mutation and elevates the level of IL-4 R which are overexpressed in HNSCC.
Alcohol: Spirit & beer: high risk whereas wine has relative low risk
Nickel & chromatic dust: carcinoma of nose, PNS, Larynx and Lung
Proto-oncogenes and tumour supressor genes: In normal situation there is a balance between these but if proto-oncogene activity is increased tumour occurs.
Apoptosis: It is a programmed cell death which maintains homeostasis. Some proto-oncogenes like bcl2 blocks apoptosis rather than stimulating cell proliferation.
Growth factors: Growth factors and their receptor signalls for cell division and cell growth under normal physiological condition. Overexpression of these factor and their receptor causes excessive cell growth e.g. EGF and EGFR, PDGF, FGF and FGFR.
Tumour immunology: Immune system constantly detect and kill the malignant cell before they can form tumour. They are supported by:
> Presence of tumour infiltrating lymphocyte in tumour (TIL)
> Increase incidence of tumour in immunosuppressed patient.
TIL are downregulated by TGF and PE2 secreted by tumour.