Background: The accumulation of mutagenic substances in the human body may result in DNA metabolism disruption followed by carcinogenesis. As a consequence of mutations in the genes coding for transmembrane protein pumps, the intracellular concentration of xenobiotics may significantly increase. This, in turn, may provoke altered risk for cancer development. The gene known to be the most relevant in the transport of numerous compounds is ABCB1 (also known as MDR1). Numerous mutations and polymorphisms that affect the encoded protein's (PgP) function were identified in this gene. The aim of the study was to define the frequency of 2677G>A,T and 3435C>T polymorphisms in a population of Polish breast cancer patients and to estimate their contribution to cancer development.
Methods: The polymorphism frequency analysis (209 patients vs. 202 control subjects) was performed either by allele-specific amplification (2677G>A,T) or by restriction fragment length polymorphism (RFLP) using the SAU3AI restriction enzyme (3435C>T) followed by verification with hybridization probe assays in a Real-Time system and sequencing.
Results: In the control group the frequency of individual 2677 genotypes was: wild homozygous GG = 34%, heterozygous G/T or G/A = 52.5% and variant homozygous AA or TT = 13.5%, while the genotype frequency in the group of studied patients was 43.5, 44.5 and 12%, respectively. In the control group, the frequency of individual 3435 genotypes was: CC = 25.4%, CT = 50.2%, TT = 24.4%, while the genotype frequency in the group of studied patients was 23, 46 and 31%, respectively.
Conclusion: Thus, no significant differences in the studied polymorphism frequencies were observed. It is then suggested that the studied polymorphisms, although probably good candidates in other tissue cancer types, might not be good predictive factors in breast cancer risk or development in Caucasians.