Association of interleukin-18 gene promoter polymorphisms with breast cancer.

Interleukin-18 [IL-18] gene promoter polymorphism is reported to be a genetic risk factor for several types of cancer. The aims of this investigation were to evaluate and compare the frequencies of IL-18 gene promoter polymorphisms at positions -137 [G/C] and -607 [C/A] in breast cancer patients and healthy controls as well as to study the contribution of these data with clinicopathological parameters at diagnosis. The studied populations comprised 250 cases with breast carcinoma and 206 healthy subjects. IL-18 gene promoter polymorphisms at positions -137 and -607 were amplified in patient and control groups using allele specific polymerase chain reaction [AS-PCR]. The frequencies of GG, GC and CC genotypes of -137 SNP were 141 [56.4%], 96 [38.4%] and 13 [5.2%] in patients vs. 110 [53.4%], 72 [34.9%] and 24 [11.7%] in controls, respectively. A significant decrease of the CC genotype was observed in patients [p = 0.04]. The frequency of the CC genotype at position -137 was also significantly higher in patients with metastasis than non-metastatic patients [21.4% vs. 4.3%] [p = 0.02]. There was no significant association between genotype frequencies at position -607 with breast cancer or its clinicopathological parameters at diagnosis. Moreover, allelic frequencies at these positions did not contribute to breast cancer incidence. The distribution of IL-18 gene haplotypes and genotype combinations were not significantly different between patients and normal control individuals. This is the first report investigating the contribution of IL-18 gene promoter polymorphisms to breast cancer. These results suggest contrast effects of IL-18 gene in cancer induction and progression. Key words: Breast cancer, IL-18, polymorphism.