Abstract
Objectives Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear. Methods Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study (n=1,691) was used, consisting of participants with a DNA sample available. Three well-known SNPs (rs3802842, rs6983267, rs10795668) were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models. Results The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC (HR, 3.2; 95% CI, 1.9 to 5.5 and HR, 1.8; 95% CI, 1.1 to 3.1, respectively) and rectal cancer (HR, 3.4; 95% CI, 1.8 to 6.6 and HR, 3.3; 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant. Conclusions This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype (i.e., colon or rectal cancer) and presence of dysglycemia merits further research.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide
Higher fasting serum glucose (FSG) was associated with an increased risk of CRC, among subjects with impaired fasting glucose (IFG; 100 ≤ FSG ≤ 125 mg/dL)
The findings were similar when we examined the relationship of FSG to CRC subgroup among the subjects with DNA data
Summary
In Korea, the standardized incidence of CRC has increased from 21.2/100,000 people in 1999 to 57.6/ 100,000 people in 2012 [1]. A steady increase in the incidence of CRC. Colonoscopy plus biopsy is the gold standard for CRC screening and diagnosis, more than half of all patients do not want to undergo this procedure because of the invasive nature and intestinal discomfort of colonoscopy [4]. Tests of serum biomarkers are more convenient and less invasive and can be better accepted as part of a routine physical examination [5], but the diagnostic value of most serum CRC markers still remains poor for most patients [6]
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