학술논문
Investigating the association between glycaemic traits and colorectal cancer in the Japanese population using Mendelian randomisation
Document Type
article
Author
Akiko Hanyuda; Atsushi Goto; Ryoko Katagiri; Yuriko N. Koyanagi; Masahiro Nakatochi; Yoichi Sutoh; Shiori Nakano; Isao Oze; Hidemi Ito; Taiki Yamaji; Norie Sawada; Masao Iwagami; Aya Kadota; Teruhide Koyama; Sakurako Katsuura-Kamano; Hiroaki Ikezaki; Keitaro Tanaka; Toshiro Takezaki; Issei Imoto; Midori Suzuki; Yukihide Momozawa; Kenji Takeuchi; Akira Narita; Atsushi Hozawa; Kengo Kinoshita; Atsushi Shimizu; Kozo Tanno; Keitaro Matsuo; Shoichiro Tsugane; Kenji Wakai; Makoto Sasaki; Masayuki Yamamoto; Motoki Iwasaki
Source
Scientific Reports, Vol 13, Iss 1, Pp 1-9 (2023)
Subject
Language
English
ISSN
2045-2322
Abstract
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.