Abstract
Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism to promote malignant transformation of colorectal cancer (CRC) and protect CRC cells against apoptosis. Recently, the analysis of GRP78 polymorphisms has already determined that GRP78 rs391957 polymorphism could predict clinical outcome in CRC patients. Thus, we tested whether GRP78 polymorphisms are related to the risk of CRC. In this study, we detected two GRP78 polymorphisms (rs391957 (C>T) and rs430397 (G>A)) in 414 CRC cases and 502 hospital-based cancer-free healthy controls in Southwest China using a polymerase chain reaction–restriction fragment length polymorphism technique. Compared with the CC genotype, carriers of CT and TT genotypes of rs391957 polymorphism had higher risks of CRC (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.06–1.83 for CT genotype and OR = 2.10, 95% CI = 1.06–4.14 for TT genotype, respectively). In CRC cases, the variant T allele was significantly associated with tumor invasion stage (P = 0.030), but not with status of lymph nodes metastasis (P = 0.052). Compared with the GG genotype, carriers of GA and AA genotypes of rs430397 polymorphism had higher risks of CRC (OR = 1.63, 95% CI = 1.23–2.15 for GA genotype and OR = 2.92, 95% CI = 1.23–6.94 for AA genotype, respectively). The rs430397 polymorphism was not associated with the clinicopathological characteristics of CRC. These data provide the first evidence that GRP78 rs391957 and rs430397 polymorphisms could serve as markers to predict the risk of CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for approximately 10% of total cancer cases
Compared with the CC homozygous genotype of Glucose-regulated protein 78 (GRP78) rs391957 polymorphism, the CT heterozygous (Adjusted odds ratios (ORs) = 1.39, 95% confidence intervals (CIs) = 1.06–1.83, P = 0.018) and TT homozygous (Adjusted OR = 2.10, 95% CI = 1.06–4.14, P = 0.033) genotypes were both significantly associated with higher risk of CRC
In this hospital-based case-control study, we found that the CT heterozygous, TT homozygous and combined (CT+TT) genotypes of GRP78 rs391957 polymorphism and the GA heterozygous, AA homozygous and combined (GA+AA) genotypes of GRP78 rs430397 polymorphism were both significantly associated with higher risk of CRC in a Chinese Han population, suggesting that the two GRP78 polymorphisms probably play potential roles in the development of CRC
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for approximately 10% of total cancer cases. Almost 60% of the CRC cases occur in the developed countries [1]. The incidence of CRC is increasing in most of the developing countries, whereas trends are either stabilizing or declining in most of the developed countries [2]. China has experienced a two- to four- fold increase in incidence of CRC in recent decades [3]. The pathogenesis of CRC is not completely understood but it is surely a multistep carcinogenic process in which genetic and epigenetic alterations accumulate sequentially [5]. Gene polymorphisms as genetic variations have been studied already in more than 35 different genes, and for several genes, association with CRC are observed [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
