Fanconi anemia (FA) patients are at high risk of developing head and neck cancer and have limited options for treatment due to their sensitivity to chemotherapy and radiation. We have recently found that FA model mice with mutations in certain aldehyde detoxifying enzymes (ALDH2, ADH5) develop oral tumors after exposure to alcohol. However, these mice are highly susceptible to bone marrow failure and leukemia, suggesting that modification to create a tissue_specific inactivation of one of the alleles will allow use of the mouse to model FA_associated oral squamous cell carcinoma (OSCC) whilst precluding loss of animals to hematopoietic defects. This would address the lack of OSCC animal models in the FA field, allowing in vivo research into carcinogenesis and treatment without the confounding factors of species mismatch and immunodeficiency in xenograft models, or genetic bias toward a cellular pathway not directly related to DNA crosslinking and FA pathway_mediated repair. This research will help to discern why alcohol and other envronmental toxins increase cancer risk.