Aim: Colorectal cancer (CRC) is a major health problem despite recent improvements in overall survival rates. Genetic polymorphisms affecting carcinogen biotransformation or DNA repair play pivotal roles in the carcinogenesis process. CYP1A1*2A (6235 T/C, rs4646903, Mspl) is thought to be associated with an increased risk of CRC because of its role in metabolic activation of polycyclic aromatic hydrocarbons; however, the results of previous studies are conflicting. In this study, a possible association between the CYP1A1*2A allele and CRC and the effect of cigarette smoking on this risk were examined in a British population. Material and Methods: A prospective case control study including 200 cases and 254 age-and-sex-matched controls was conducted with British participants from the north-east of England. Genotyping of the CYP1A1*2A allele was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Results: CYP1A1*2A was not associated with CRC development (OR = 1.566; 95% confidence interval [CI] = 0.90-2.73; p = 0.12). However, it was observed that C allele-carrying individuals who had smoked within the past 5 years had a significant risk of CRC (OR = 2.28; 95% CI = 1.07-4.86; p = 0.043). Conclusion: These data are of interest in understanding CRC etiology and identifying an individual's risk of developing CRC. However, a full evaluation of an association between CYP1A1*2A and cancer susceptibility in Europeans is difficult and will require a larger number of participants.