학술논문
Investigating the association between glycaemic traits and colorectal cancer in the Japanese population using Mendelian randomisation.
Document Type
Article
Author
Hanyuda, Akiko; Goto, Atsushi; Katagiri, Ryoko; Koyanagi, Yuriko N.; Nakatochi, Masahiro; Sutoh, Yoichi; Nakano, Shiori; Oze, Isao; Ito, Hidemi; Yamaji, Taiki; Sawada, Norie; Iwagami, Masao; Kadota, Aya; Koyama, Teruhide; Katsuura-Kamano, Sakurako; Ikezaki, Hiroaki; Tanaka, Keitaro; Takezaki, Toshiro; Imoto, Issei; Suzuki, Midori
Source
Subject
*COLORECTAL cancer
*JAPANESE people
*SINGLE nucleotide polymorphisms
*GENETIC epidemiology
*GENOME-wide association studies
*INSULIN aspart
*FETAL hemoglobin
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Language
ISSN
2045-2322
Abstract
Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99–1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60–1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97–2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies. [ABSTRACT FROM AUTHOR]