Abstract
Previous studies have found that common genetic variants on chromosome 8q24 are associated with the risk of developing colorectal neoplasia. We conducted a hospital-based case-control study, including 435 cases and 788 unrelated controls to investigate the associations between common variants on 8q24 and the risk of colorectal cancer in a Chinese population. We also evaluated the association of rs6983267 with colorectal neoplasia in the published literature via a meta-analysis study. We found that rs6983267 was significantly associated with the risk of colorectal cancer in the Chinese population, with an adjusted odds-ratio (OR) for the GT heterozygotes and GG homozygotes of 1.30 (95% CI = 0.98–1.71, P = 0.069) and 1.66 (95% CI = 1.18–2.34, P = 0.004), respectively, compared to the TT homozygotes, with a P-trend value of 0.003. No association was found for the other three loci (rs16901979, rs1447295 and rs7837688). In the meta-analysis of the published genetic association studies, the rs6983267 variant was found to be associated with an increased risk of colorectal neoplasia. The heterozygous GT carriers showed a 20% increased risk of colorectal neoplasia (OR = 1.20, 95% CI = 1.16–1.25; random effects model) with a summary OR for homozygous GG carriers of 1.39 (95% CI = 1.32–1.48; random effects model) compared to the TT genotype carriers. We found no significant differences between the association of rs6983267 and colorectal cancer and colorectal adenomas. In summary, our study confirms that the variant rs6983267 is a risk factor for colorectal neoplasia in various populations, including the Chinese population.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide [1]
The medical records of the patients were thoroughly checked and for those who were suffering from ileocecal junction tumors or anal canal tumors and those with any of the following conditions: i. recurrence of CRC; ii. familial adenomatous polyposis (FAP); iii. hereditary nonpolyposis colorectal cancer (HNPCC); iv. other tumors; v. severe digestive tract diseases lasting over 2 years; vi. diabetes, fatty liver, hepatic cirrhosis, metabolic syndrome or severe cardiovascular diseases were excluded from the study
For the GG homozygotes, we noted that there was a significant increase in colorectal neoplasia, with the summary odds ratio (SOR) of 1.40 under the fixed effects model and 1.39 under the random effects model compared to the TT carriers (Figure 3)
Summary
Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide [1]. Among the risk factors and causes for CRC, inherited genetic factors account for approximately 35% of the disease etiology [2]. Many genetic factors, such as mutations of critical genes (e.g. APC, MLH1, MSH2, TGFBR2 and SMAD4) have been identified [3]. In the past few years, several genome-wide association studies (GWAS) have identified novel loci that are associated with CRC risk, such as variants on 11q23 [2], 8q24 [4,5,6], 10p14 [7], 8q23.3 [7], 15q13.3 (HMPS) [8] and SMAD7 [9]. The extent to which these genetic factors contribute to the disease has not been established
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