Genetic analysis of colorectal carcinoma using high throughput single nucleotide polymorphism genotyping technique within the population of Jammu and Kashmir.

BACKGROUND: SNP genotyping has become increasingly more common place to understand the genetic basis of complex diseases like cancer. SNP-genotyping through MassARRAY™ is a cost-effective method to quantitatively analyse the variation of gene expression in multiple samples, making it a potential tool to identify the underlying causes of colorectal carcinogenesis. METHODS: In the present study, SNP genotyping was carried out using Agena MassARRAY™, which is a cost-effective, robust, and sensitive method to analyse multiple SNPs simultaneously. We analysed 7 genes in 492 samples (100 cases and 392 controls) associated with CRC within the population of Jammu and Kashmir. These SNPs were selected based on their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with colorectal cancer within the J&K population.7 SNPs with a call rate of 90% were selected for the study. Out of these, five SNPs rs2234593, rs1799966, rs2229080, rs8034191, rs1042522 were found to be significantly associated with the current study under the allelic model with an Odds Ratio OR = 2.981(1.731-5.136 at 95% CI); p value = 4.81E-05 for rs2234593,OR = 1.685(1.073-2.647 at 95% CI);; p value = 0.02292 for rs1799966, OR = 1.5 (1.1-2.3 at 95% CI), p value = 0.02 for rs2229080, OR = 1.699(1.035-2.791 at 95% CI); p value = 0.03521 for rs8034191, OR = 20.07 (11.26-35.75); p value = 1.84E-34 for rs1042522 respectively. CONCLUSION: This is the first study to find the relation of Genetic variants with the colorectal cancer within the studied population using high throughput MassARRAY™ technology. It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Genetic variants of DNAH11 and LRFN2 genes and their association with ovarian and breast cancer.

OBJECTIVE: To investigate the association of newly identified genetic variants G>A (rs2285947) of the DNAH11 gene and G>A (rs2494938) of the LRFN2 gene with ovarian and breast cancers in women belonging to Jammu and Kashmir state, where the prevalence of ovarian and breast cancers is remarkably high in the population. METHODS: A candidate gene prospective case-control association study design was adopted, in which 354 cases (219 cases of ovarian cancer and 135 cases of breast cancer) were histopathologically confirmed and 330 healthy controls matched for age and ethnicity were recruited. The details of cases and controls were also recorded in a predesigned pro forma after their written informed consent. Both variants were genotyped by TaqMan allele discrimination assay using real-time polymerase chain reaction. Logistic regression analysis was performed to estimate the corrected odds ratio (OR), confidence interval (CI), and level of significance (P value) for potential confounding factors. RESULTS: The rs2285947 variant of DNAH11 was found to be significantly associated with both ovarian and breast cancers with adjusted ORs of 1.7 (95% CI 1.2-2.4; P=0.004) and 1.70 (95% CI 1.13-2.54; P=0.0009), respectively. However, no significant association of variant rs2494938 of LRFN2 was observed with ovarian cancer (estimated OR 0.9, 95% CI 0.6-1.4; P=0.919) or breast cancer (estimated OR 1.27, 95% CI 0.8-1.9; P=0.216). CONCLUSIONS: The collected data proposed that the variant rs2285947 of DNAH11 gene is a potential risk factor for ovarian and breast cancers in the studied population.