The largest area of interaction between host and environment in humans is between intestinal epithelium and luminal contents. Variations in genetic factors together with xenobiotic exposure to compounds from diet, cigarette smoke, drugs, bacterial toxins or others are associated with increased risk of colorectal cancer. Therefore, the MDR1 efflux pump could be a possible link between genetic and environmental factors for colorectal cancerogenesis.

In our study 146 Bulgarian patients (76 women and 71 men; ratio 1:1,1) at mean age 65+/-9 were enrolled for genotyping of two SNPs, located in exon coding regions in MDR1 (3435 C>T and 2677 G>T). The results were compared to the results of a control group which consisted of 160 unrelated healthy Bulgarian volunteers (84 women and 76 men; ratio 1:1,1) at mean age 59+/-10. Gene polymorphisms were identified using rapid-cycle real-time amplification with allele specific probes and subsequent melting curve analyses on a LightCycler (Roche Diagnostics).

The observed allele and genotype frequencies among the patient and control groups were summarized in table 1. The frequencies of all genotypes were in Hardy–Weinberg equilibrium in both groups. Our results showed that the frequencies of MDR1 polymorphisms 3435 C>T  and 2677 G>T did not correlate with colorectal tumorigenesis.

We also analyzed the MDR1 polymorphisms in both tumor and normal intestinal tissues of 80 patients and concluded that no evidence of somatic mutations was observed in the tumor samples as genotypes always matched with those of the corresponding normal tissue samples.

Table 1. Allele and genotype frequencies of MDR1 3435 C>T and 2677 G>T in patients with colorectal cancer and healthy volunteers of Bulgarian origin

SNPs in MDR1	Patients (N=146)		Controls (N=160)		P-value
	n	Frequency	n	Frequency
3435 C>T wt allele m allele Genotypes wt/wt wt/m m/m	151 141   36 79 31	0,517 0,483   0,247 0,541 0,212	157 163   43 71 46	0,491 0,509   0,269 0,444 0,287	0,512     0,199
2677 G>T wt allele m allele Genotypes wt/wt wt/m m/m	165 127   46 73 27	0,565 0,435   0,315 0,500 0,185	179 141   55 69 36	0,559 0,441   0,344 0,431 0,225	0,888     0,458
wt allele-wild-type allele; m allele-variant allele; N-number of studied individuals; n-number of alleles or number of heterozygous, homozygous