Gene environment interactions: Cigarette smoke, APC, DNA damage repair, and human health

Cigarette smoking extensively affects public health across the globe. Smokers have a high incidence of lung cancer, but also have been linked with other cancers, such as breast, colon, larynx, oral cavity, pharynx, esophagus, pancreas, kidney and bladder. Apart from cancer development, cigarette smoking is associated with the depletion of circulating antioxidant micronutrient concentrations, increased inflammation, impaired immune status, altered lipid profiles, respiratory symptoms, nicotine addiction, diabetes, periodontitis, asthma exacerbation, vascular diseases and chronic obstructive pulmonary disease (COPD). One of the critical factors by which cigarette smoking causes cancer development is the DNA damage that has been recently proved by effectively mapping the cigarette smoke-induced DNA damage at high resolution across the genome. If the damage of genomic DNA is not efficiently repaired by DNA repair machinery, then it may induce gene mutations, resulting in the initiation of carcinogenesis. Cigarette smoke not only causes problems to active smokers but to the passive or secondhand smokers as well. The focus of this chapter is to discuss molecular mechanisms that involve the repair of cigarette smoke-induced DNA damage with special emphasis on the tumor suppressor APC (adenomatous polyposis coli) that impairs cigarette smoke-induced base excision repair pathway and induces malignant transformation of breast epithelial cells.