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C-C motif chemokine 22 (CCL22) C16A genetic variation (rs4359426) and C-C chemokine receptor type 4 (CCR4) C1014T variation (rs2228428) have been suggested to affect the expression level of the cognate proteins. Here we tried to investigate the plausible association of these polymorphisms with development of colorectal cancer. 165 patients with colorectal adenocarcinoma (age 54.4±13.4) and 150 age- and sex-matched healthy individuals were enrolled. Genotyping was performed by PCR-RFLP methods. Results indicated the frequency of 16A allele in CCL22 gene to be 31/330(9.4%) and 33/300(11%) in patients and controls, respectively (p=0.59). The frequencies of CC, CA, and AA genotypes at this locus were not significantly different between patients and controls (135/165; 81.8%, 29/165; 17.6%, 1/165; 0.6% in the patients and 121/150; 80.1%, 25/150; 16.6% and 4/150; 2.6% in the control group, p= 0.34). At the locus 1014 in CCR4, T allele was observed with the frequency of 107/330 (32.4%) and 83/300 (27.7%) in patients and controls, respectively (p=0.22). Analyses indicated no significant differences in the frequencies of CC, CT and TT genotypes at this locus between patients and controls (77/165; 46.7%, 69/165; 41.8% and 19/165; 11.5%; versus 83/150; 55.0%, 51/150; 33.8% and 16/150; 10.6%, respectively, p= 0.29). The presence of individual genotypes was not associated with clinicopathological characteristics of the disease, including tumor size, tumor grade and LN involvement (all with p<0.05). These findings collectively suggested that CCR4 C1014T and CCL22 C16A genetic variations were neither associated with the risk, nor with the progression of colorectal cancer in Iranian population.