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Background: Heat Shock Proteins (HSP’s) are expressed at high levels in wide range of tumors. They are determining factors for tumor cell survival as they promote autonomous cell proliferation, inhibit cell death pathways, delay senescence as well as influence the immune response to tumor cells. Purpose of the study: We designed a large scale case-control study to characterize the frequency of two polymorphisms within the MHC classIII-linked HSP70 genes, Hsp70-2 and Hsp70-hom, in order to find any association of these genotypic variants for predisposition to and clinical outcome of breast carcinoma patients from Kashmir valley in North India. Polymerase Chain Reaction and restriction enzymes were utilized to characterize the frequency of two polymorphisms with in Hsp70-2 and Hsp70-hom genes in 114 breast carcinoma cases and 90 healthy controls from the same population of Kashmir. Association of high frequency allelic/genotypic variants of Hsp70genes with various clinicopathological features of prognostic significance was assessed by Chi-square test using SPSS software. Results: In the present study, allelic frequency of Hsp70-2 A/G heterozygote (0.88) (p=0.008) was found to be significantly high in breast carcinoma cases compared to control (0.744) with a Relative Risk =2.67 fold. Conversely, the allelic frequency of Hsp70-2A/A allele in homozygous condition was significantly low in breast carcinoma cases and worked out to be 0.078 (Vs 0.244 in control) with p=0.001, implicating it as a protective allele against breast cancer in subjects with this genotype. Similarly, significantly high frequency of 0.50 (Vs 0.30 in control) of Hsp70-homC/C allele was found in homozygous condition in breast cancer cases suggestive of a positive relative risk associated with this genotype (RR=2.42) (p=0.003). The overall genotype frequency data analysis of Hsp70-2 and Hsp70-hom genes was significant (χ2=11.46, p=0.003; and χ2=10.56, p=0.005). The study also reveals considerable association of high frequency alleles of HSP70 genes, especially of Hsp70-2A/G or G/G in breast tumors with clinico-pathological features of poor prognosis. Conclusion: These results indicate that the relative risk of breast cancer associated with Hsp70-2 and Hsp70-hom gene polymorphisms is confined to Hsp70-2 A/G or G/G and Hsp70homC/C haplotype in our population. The study, therefore, suggests Hsp70-2A/G orG/G and Hsp70homC/C genotypes as potential susceptibility markers and independent prognostic indicators in breast carcinoma patients in Kashmiri population.
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Author(s): Rafiqa Eachkoti Hakim Ali Qanoon Pervaiz A Koul Sabhiya Majid Dilafroze
Breast cancer, Hsp-70-2, Hsp70-hom, Kashmir, India