Authors: Khaled A. Habeb, Maysaa Ghazi. Jumaah.
The present study aimed to shed light on the association between the gene expression of IL8 and its genetic polymorphism IL-8 A251T in the incidence and pathogenesis of ovarian cancer. A total of 43 Paraffin-embedded tissue blocks from patients with different stages of newly diagnosed ovarian cancer were provided by certain Iraqi hospitals as well as 14 samples of patients with benign ovarian tumors tissues as a control group were used in this study. In the present study, the level of IL8 gene expression was investigated by comparing it with that of benign tumors, the results detected that IL-8 mRNA was expressed in 47(81.02%) of samples, 36 samples with ovarian cancer and 11 benign ovarian. IL-8 mRNA levels in ovarian cancer tissues were statically significant higher than those in benign ovarian tissue (P=0.0328<0.05). The samples were divided into high and low mRNA-expression depending on the mean value of IL8 gene expression in benign tumors which used as a cutoff, the results showed that samples with high mRNA-expressing 25(69.4%) which showed high significant differences compare with samples that showed low expressing 11(30.55%) (P value=0.0028<0.01). In correlation with histopathological type of ovarian tumors, mucinous tumors showed statistically significant difference in compare with other histopathologic tumor type (P=0.0516,<0.05). According to the tumor stages, statistically significant difference was found between 31(86.11%) of samples with stage I which showed the highest level of expression and 5(13.88%) of samples with stage III (P value=0.0410<0.05). For A251T polymorphism, the result showed that 21(58.33%) patients were heterozygous A/T, 14(38.88%) were homozygous T/T, and 1(2.77%) was homozygous A/A. For patients with benign ovarian tumors 11(91.66%) were heterozygous A/T, 1(8.33%) was homozygous T/T, and no one of the patients were homozygous for the A/A genotype. High significant prevalence of the IL-8 251T allele was detected in both ovarian cancer patients (P value 0.0047 <0.01) and patients with benign ovarian tumors (P value 0.014 <0.02) as compared with IL-8 251A allele. In the present study the association of the A251T polymorphism with ovarian cancer were investigated by attending to levels of IL-8 mRNA in benign and malignant ovarian tissues related with the respective genotypes. In benign ovarian tumors statically analysis showed that there were no significant differences between genotypes, while for cancer samples, the average of IL-8 gene expression in ovarian cancer patients carrying +251TT genotype was highly significant than that in ovarian cancer patients with the +251AT and +251AA genotypes (p value= 0.0037<0.01). In conclusion, the results reflected the possibility of detecting the IL8 gene transcript in benign as well as the malignant ovarian tissues but with wide differences in the sample percentages and level of gene expression which in turn reflect the value of IL8 gene as a useful tool for discriminating malignant breast tumors from non-malignant ones. On the other hand the high level of gene expression associated with stage I of tumor may be reveals the diagnostic value of this gene for early diagnosis of ovarian cancer. The results showed that the genetic variation of IL-8 gene influences susceptibility to ovarian cancer, we also suggested that the TT genotype of IL-8 -251A/T may associate with increase the risk of ovarian cancer in Iraqi women because of altered IL-8 gene expression.
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