ABSTRACT. Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allelespecific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.

Systemic lupus erythematosus (SLE)is an autoimmune disorder whereby the immune system's components act upon our body's self-antigens. The pathogenesis is mainly due to the hyperactivity of T helper cells and B lymphocytes, as well as an abnormal apoptosis pathway. SLE has been linked to several genes, including the interleukin-1 beta (IL-1β), as it is primarily involved in the stimulation of B cells proliferation and differentiation, as well as costimulation of T cell activation, together with activation of natural killer (NK) cells. This study aims to examine the distribution pattern and association of IL-1β single nucleotide polymorphisms (SNPs) with SLE. A total of 100 SLE patients and 100 matched normal healthy controls were sampled. The analysis of IL-1β −511 C/T and +3954 E1/E2 SNPs were carried out via polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). A significant association was observed between the IL-1β −511 C/T polymorphisms and the Malaysian SLE samples ( p < 0.05), with the C allele showing a higher risk to SLE compared to the T allele. The IL-1β +3954 E1/E2 polymorphisms were also significant to SLE ( p < 0.05), with the E1 allele exhibiting a relatively higher disease penetration compared to the E2 allele. Both SNPs analysed were found to be significantly corelated with Malaysian SLE samples.

ABSTRACT. Systemic lupus erythematosus (SLE) is an autoimmune disease that causes systemic damage, involving auto-reactive antibodies and over-deposition of immune complexes. Susceptibility to SLE is believed to be multifactorial, and genetics is one of the proven etiological factors; it can affect SLE development, severity and prognosis. We investigated a possible association between the angiotensin-converting enzyme gene and susceptibility to SLE in the Malaysian population. PCR was employed for the determination of I/D dimorphism of this gene. The I allele was more frequent than the D allele in both the SLE patients (N = 170) and healthy controls (N = 190). However, there was no significant difference in the distribution of these two alleles between both groups studied (χ 2 = 0.284, P > 0.05). Interestingly, the DD homozygous genotype scored notably higher in the healthy control group (χ 2 = 7.568, P < 0.05), while the ID heterozygote was observed to be significantly associated with SLE (χ 2 = 11.143, P < 0.05). In conclusion, with respect to the Malaysian population, the DD genotype might play a protective role in the development of SLE while in contrast, those who carry the ID genotype might be at potential risk for onset of this disease.

ABSTRACT. This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ 2 = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.

X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.