Interleukins (ILs)—which are important members of cytokines—consist of a vast group of molecules, including a wide range of immune mediators that contribute to the immunological responses of many cells and tissues. ILs are immune-glycoproteins, which directly contribute to the growth, activation, adhesion, differentiation, migration, proliferation, and maturation of immune cells; and subsequently, they are involved in the pro and anti-inflammatory responses of the body, by their interaction with a wide range of receptors. Due to the importance of immune system in different organisms, the genes belonging to immune elements, such as ILs, have been studied vigorously. The results of recent investigations showed that the genes pertaining to the immune system undergo progressive evolution with a constant rate. The occurrence of any mutation or polymorphism in IL genes may result in substantial changes in their biology and function and may be associated with a wide range of diseases and disorders. Among these abnormalities, single nucleotide polymorphisms (SNPs) can represent as important disruptive factors. The present review aims at concisely summarizing the current knowledge available on the occurrence, properties, role, and biological consequences of SNPs within the IL-1 family members.

Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.

Inflammation constitutes one of the important components of colorectal cancer (CRC) pathogenesis. Tumor necrosis factor-α (TNF-α), a cytokine and an important inflammatory mediator plays a pivotal role in the malignant cellular proliferation, angiogenesis, tissue invasion and metastasis in CRC. The studies on association of various polymorphisms in human TNF-α gene including TNF-α-308G/A single nucleotide polymorphism (SNP) are limited, mixed and inconclusive. The aim of this study was to analyze the association of TNF-α-308G/A promoter SNP with colorectal cancer (CRC) susceptibility and development risk and also to evaluate the modifying effects of possible TNF-α-308G/A genotypes on different risk factors of CRC in ethnic population of Kashmir, India through a case-control setup. The genotype frequencies of TNF-α-308G/A promoter SNP were compared between 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The associations between the TNF-α-308G/A SNP and CRC risk were examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. Further, the associations between this SNP and various clinico-pathological parameters, demographic variables and environmental factors within the case group subjects with regard to CRC risk were also evaluated. The association between the TNF-α-308G/A SNP and the modulation of risk of CRC was not found to be significant (p value = 0.156). The effect of less common TNF-α-308A allele on the risk of colorectal cancer was also not found to be significant (p value = 0.175). The variant genotype (AA) was nonexistent in the study population. Further, we found no significant effect modulation of CRC risk by wild and heterozygous TNF-α-308G/A SNP genotypes in presence of different possible risk factors (p > 0.05). We also found no significant association of TNF-α-308G/A SNP with the subsets of various characteristics of the case group subjects under study (p > 0.05). This study indicates that there is no significant association between the TNF-α-308G/A promoter SNP and the risk of developing CRC in ethnic Kashmiri population. However, in order to substantiate our findings, this study needs to be replicated with bigger sample size and should involve other ethnically defined populations with high CRC risk.

The aim of this study was to investigate the role of the XRCC1 Arg399Gln polymorphism in the susceptibility of a Kashmiri population to colorectal cancer (CRC). We investigated the genotype distribution of the XRCC1 gene in 130 CRC cases in comparison with that of 150 healthy subjects. There was no direct significant association between the XRCC1 genotypes and CRC; however, the Arg/Gln genotype was associated with an elevated risk of CRC (OR>1.47) and the Gln/Gln variant genotype was associated with an increased risk of CRC in various clinicopathological parameters. This study suggests that the XRCC1 polymorphism is associated with an increased risk of CRC.

Chronic inflammation increases the risk of development of various cancers, including colorectal cancer. Interleukin-6 has been described as a key regulator of colorectal cancer development and is important in the process of colorectal tumorigenesis largely through the regulation of tumor-promoting inflammation. Several studies have reported the association of various polymorphisms in human interleukin-6 gene including IL-6 −174G/C single nucleotide polymorphism with various cancers, including colorectal cancer, but the results are mixed and inconclusive. The aim of this study was to analyze the association of IL-6 −174G/C promoter single nucleotide polymorphism with colorectal cancer risk and also to evaluate the modifying effects of possible IL-6 −174G/C single nucleotide polymorphism genotypes on different risk factors of colorectal cancer or the reciprocal effect in ethnic Kashmiri population through a case control setup. The genotype frequencies of IL-6 −174G/C promoter single nucleotide polymorphism were compared between 142 colorectal cancer patients and 184 individually matched healthy controls by using polymerase chain reaction–restriction fragment length polymorphism method. The association between the IL-6 −174G/C single nucleotide polymorphism and colorectal cancer risk was examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. The possible effect measure modification of the association between the relevant single nucleotide polymorphism genotypes and colorectal cancer risk by various colorectal cancer risk factors including age, gender, and smoking status was also evaluated. Furthermore, the associations between these single nucleotide polymorphisms and various clinicopathological parameters, demographic variables, and environmental factors within the case group subjects with regard to colorectal cancer risk were also analyzed. The overall association between the IL-6 −174G/C single nucleotide polymorphism and the modulation of colorectal cancer risk was found to be highly significant (p = 0.001). The variant genotype (CC) was significantly associated with a decreased risk of colorectal cancer (odds ratio, 0.15 (95% confidence interval, 0.04–0.54); p = 0.004). Furthermore, the less common IL-6-174C allele was associated with a decreased risk of colorectal cancer (odds ratio, 0.49 (95% confidence interval, 0.33–0.73); p = 0.0006). The combined variant genotype (GC + CC) was also significantly associated with a decreased risk of colorectal cancer (odds ratio, 0.54 (95% confidence interval, 0.33–0.89); p = 0.015). This study demonstrates that there is a strong and highly significant association between the IL-6 −174G/C promoter single nucleotide polymorphism and a decreased risk of colorectal cancer in ethnic Kashmiri population. However, in order to substantiate our findings, this study needs to be replicated with larger sample size and with other ethnically defined populations with comparable colorectal cancer incidence.