TP53 Codon 72 Genetic Polymorphism, rs1042522, Modifies the Association Between Tobacco Smoking and Breast Cancer Risk

Background TP53 tumor suppressor gene participates in several pathways involving in carcinogenesis such as cell cycle control, DNA repair, and apoptosis. A common TP53 SNP (guanine/cytosine nucleotide substitution at codon 72), rs1042522, affects the function of p53 protein and may influence tumor behavior in response to environmental carcinogens. Objectives This study investigates the association between TP53 codon 72 polymorphisms, tobacco smoking, and breast cancer risk in southern Iranian women from Bushehr. Methods A case-control study was conducted on 144 cases with histologically confirmed invasive breast carcinoma and 162 randomly selected healthy controls with no previous cancer history in their family. TP53 codon 72 genotype was determined by using restriction fragment length polymorphism- polymerase chain reaction (RFLP-PCR) technique. Results Analysis revealed that smoking frequency was significantly higher in cases compared to controls (OR = 2.31, 95%CI = 1.33-3.99, P = 0.003) and the association between smoking and breast cancer was only significant for individuals with Arg/Pro genotype (OR = 3.23, 95% CI = 1.47 - 7.06, P = 0.003). On the other hand, there was no statistically considerable difference in the allele and genotype distribution between cases and controls. Conclusions These results should be confirmed in larger studies, but suggest that TP53 Arg/Pro genotype modifies the risk of breast cancer in tobacco smokers and causes significantly more susceptibility to breast cancer due to smoking.