Several candidate polymorphisms in the caspase 8 gene have been reported recently in public databases (http://www.ncbi.nlm.nih.gov/SNP
). So, some of these SNPs in the genome, with a high degree of variability make these informative genetic markers useful for disease susceptibility. Therefore, these variants may influence CASP-8 activity, thereby modulating susceptibility. Genetic polymorphisms in the caspase genes may influence cancer risk by altering expression levels and functions of these genes. In recent years, genetic variants in caspase mediated apoptosis and their role in human cancer susceptibility have been getting more and more attention, especially the apoptosis initiator caspase 8. Due to marked differences in the distribution of caspase gene polymorphisms between various ethnicities, the data from “normal healthy” populations are of special interest for the adequate evaluation of the relevance of the investigated genetic markers in susceptibility, manifestation, prognosis or treatment of diseases. However, it is noteworthy to conduct extensive investigations about the distribution of these genes in different ethnic groups.
The variation in our Indian population from other world population signifies the impact of ethnicity. It is well recognized that ethnic background may influence the susceptibility to certain diseases.[14
] Due to the different socio-cultural traditions, Indian population is believed to be most diverse. Future implications for preventive and early intervention strategies in cancer can therefore be accomplished by the study of genetic variation, which can elucidate critical determinants in environmental exposure and cancer. The differences in allele frequencies detected among these studies might be due to ethnic variation, heterogeneity of study populations and/or different sample sizes, as there have been very different selective pressures driving different disease susceptibilities in genetically heterogeneous populations.[15
In the CASP 8 IVS12-19G/A polymorphism, the (A) allele frequency in Indian population was 17.6%, whereas it was significantly higher in Korean and Chinese subjects (28.5 and 28.3%, respectively). The (H) allele frequency in CASP D302H polymorphism was 13.2% in our population. No significant difference was observed in the populations from Sheffield, East Anglia, among the Non-Hispanics and from USA. In CASP -652del polymorphism, the (Del) allele frequency in Indian population was 23.2%, which was significantly different and higher in German and Polish subjects while it was the same in China. On the other hand, the allele frequency for CASP8 -678del, (Del) allele was 24.6 which was the same as in Korean subjects.
The minor variant allele frequencies of Sheffield, East Anglia, Non-Hispanics and USA were found to be almost similar to that of our northern population for CASP 8 D302H
(13.2% vs. 16%, 13%, 14% and 14.1%, respectively), a similar pattern was observed in case of CASP 8 -678del
(24.6% vs. 23.7%) in our population and in a study by Son et al
. (2006) in Korean population This suggested that gene variants were unaffected based on geographic location. Unlinked genes undergo more or less independent changes in allele frequency; this produces geographically cross-cutting allele frequency clines found among genes.[14
One way to determine what is driving health disparities is to have more focused genetic research within specific identifiable populations whose unusually high (or low) risk or population history makes them advantageous for finding susceptibility genes.[17
] But this raises the potential danger that the disease might be racialized using the new genetic information.[18
] The advantage of such kind of study may form the basis for future establishment of epidemiologic and clinical databases. Population differences in disease incidence and mortality are due to a range of genetic and socio-cultural factors. Health disparities among populations are well documented, yet poorly understood. Susceptibility genotypes are shared across our species, race or equivalent socio-culturally defined measures are often highly correlated with socioeconomic or other environmental or lifestyle factors. The same genotype may have very different risks in different environments, and this can mean in different populations; secular trends for most major diseases show clearly that this is the typical case.[14
Therefore, our observation suggests that CASP 8 polymorphisms with their variants could be used as biomarkers for disease susceptibility and may be used for assessing the risk of cancer development. A single larger study with thousands of subjects and tissue-specific biochemical and biological characterization is warranted to further evaluate potential gene-to-gene and gene-to-environment interactions on CASP gene polymorphisms and cancer risk. The differences in the distribution of these genes between North Indian healthy population and other ethnic groups may help in building a silhouette that would help in assessing the disease predisposition and prevalence. More emphasis is needed on evaluating polymorphisms, alone or in combinations, as modifiers of risk from relevant environmental/lifestyle exposures.