Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control.

The ability to metabolise carcinogens or pro-carcinogens, repair DNA damage, and control cell signalling and the cell cycle are fundamental to homeostasis. Oral squamous cell carcinoma (oral cancer) and many squamous cell carcinomas of the head and neck (SCCHN) may, under appropriate exposure to mutagens, arise if these mechanisms are defective. SCCHN arise as a consequence of multiple molecular events induced by the effects of various carcinogens from habits such as tobacco use, influenced by environmental factors, possibly viruses in some instances, against a background of heritable resistance or susceptibility. Consequent genetic damage affects many chromosomes and genes, and it is the accumulation of these changes that appears to lead to carcinoma in some instances, sometimes via a clinically evident pre-malignant, or potentially malignant, lesion. Although lifestyle factors play a prominent role in aetiology, some patients appear susceptible because of an inherited trait in their ability or inability to metabolise carcinogens or pro-carcinogens, possibly along with an impaired ability to repair the DNA damage. This is the first of a series of three papers reviewing the advances in the understanding of this area of research since our last review [Scully C, Field JK. Genetic aberrations in squamous cell carcinoma of the head and neck (SCCHN), with reference to oral carcinoma (Review). Int J Oncol 1977;10:5-21] and discusses mainly oral carcinoma in the context of SCCHN.