Polymorphic analysis of MHClinked Heat Shock Protein 70 genes: Their susceptibility and prognostic implication in Kangri cancer cases of Kashmiri population

Abstract

Kangri cancer is a unique thermally-induced squamous cell carcinoma (SCC) of skin that develops due to persistent use of Kangri (a brazier), used by Kashmiri people, to combat the chilling cold during winter months. We designed a large scale case-control study to characterize the frequency of two polymorphisms within the MHC class III-linked HSP70genes, Hsp70-2 and Hsp70-hom, in order to find any association of these genotypic variants for predisposition to and clinical outcome of Kangri cancer 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 118 Kangri carcinoma cases and 95 healthy controls from the same population of Kashmir. Association of high frequency allelic variants of Hsp70genes with various clinicopathological features of prognostic significance was assessed by Chi-square test using SPSS software. In this study, allelic frequency of Hsp70-2 A/G heterozygote (0.87) (P = 0.012) was found to be significantly high in Kangri cancer cases compared to control (0.736) with a Relative Risk of 2.45 fold. Conversely, the allelic frequency of Hsp70-2 A/A allele in homozygous condition was significantly low in Kangri cancer cases and worked out to be 0.084 (Vs 0.252 in control) with P is equal to 0.001, implicating it as a protective allele against Kangri cancer in subjects with this genotype. Similarly, significantly high frequency of 0.50 (Vs 0.29 in control) of Hsp70-homC/C allele was found in homozygous condition in Kangri cancer cases suggestive of a positive relative risk associated with this genotype (RR is equal to 2.47) (P is equal to 0.002). The overall allele frequency data analysis of Hsp70-2 and Hsp70-hom genes was significant (χ2 is equal to 12.38, P is equal to 0.002; and χ2 is equal to 12.21, P is equal to 0.002). The study also reveals considerable association of high frequency alleles of HSP70 genes, especially of Hsp70-2 A/G or G/G in Kangri tumors with clinico-pathological features of poor prognosis. These results indicate that the relative risk of Kangri 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 Hsp70-2 A/G or G/G and Hsp70homC/C genotypes as potential susceptibility markers and independent prognostic indicators in Kangri carcinoma patients in Kashmiri population.

Heat Shock Protein 70 Gene Polymorphisms and Cancer Risk: A Meta-Analysis

“…3 studies focused on hepatocellular carcinoma, 3 studies on gastric cancer, 3 studies on breast cancer, and 11 studies on others (2 on lung, childhood acute lymphoblastic leukemia (ALL) and one on colorectal, pancreatic, prostate, and Kangri cancer, multiple myeloma, and non-Hodgkin's lymphoma, resp.). The distribution of genotypes in the controls was consistent with the Hardy-Weinberg equilibrium for all selected studies except for six studies [ 11 , 19 , 20 , 23 , 28 ] for HSP70-2 polymorphism and four studies [ 18 , 20 , 26 ] for HSP70-hom polymorphism.…”

Overexpression of HSPA2 is correlated with poor prognosis in esophageal squamous cell carcinoma

“…Overexpression of HSPA2 is correlated with poor therapeutic outcomes in human breast cancer, cervical cancer and bladder urothelial cancer; furthermore, it is now a valuable prognostic marker for breast cancer patients [7]. The polymorphism of HSPA2 acts as an attractive susceptibility marker and independent prognostic indicator in Kangri cancer patients [30]. Considering the frequency of positivity of HSPA2 in adjacent non-cancerous tissues is much higher, whether or not HSPA2 molecule can be qualified to be a prognostic biomarker will need to be validated in future clinical work.…”