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Suzuki, Shiori National Cancer Center|Jikei University School of Medicine
Goto, Atsushi National Cancer Center|Yokohama City University
Nakatochi, Masahiro Nagoya University
Narita, Akira Tohoku University
Yamaji, Taiki National Cancer Center
Sawada, Norie National Cancer Center
Katagiri, Ryoko National Cancer Center
Iwagami, Masao University of Tsukuba
Hanyuda, Akiko National Cancer Center
Hachiya, Tsuyoshi Iwate Medical University
Sutoh, Yoichi Iwate Medical University
Oze, Isao Aichi Cancer Center Research Institute
Koyanagi, Yuriko N. Aichi Cancer Center Research Institute
Kasugai, Yumiko Aichi Cancer Center Research Institute|Nagoya University
Taniyama, Yukari Aichi Cancer Center Research Institute
Ito, Hidemi Aichi Cancer Center Research Institute|Nagoya University
Ikezaki, Hiroaki Kyushu University
Nishida, Yuichiro Saga University
Tamura, Takashi Nagoya University
Mikami, Haruo Chiba Cancer Center Research Institute
Takezaki, Toshiro Kagoshima University
Suzuki, Sadao Nagoya City University
Ozaki, Etsuko Kyoto Prefectural University of Medicine
Kuriki, Kiyonori University of Shizuoka
Takashima, Naoyuki Kindai University|Shiga University of Medical Science
Takeuchi, Kenji Nagoya University
Tanno, Kozo Iwate Medical University
Shimizu, Atsushi Iwate Medical University
Tamiya, Gen Tohoku University
Hozawa, Atsushi Tohoku University
Kinoshita, Kengo Tohoku University
Wakai, Kenji Nagoya University
Sasaki, Makoto Iwate Medical University
Yamamoto, Masayuki Tohoku University
Matsuo, Keitaro Aichi Cancer Center Research Institute|Nagoya University
Tsugane, Shoichiro National Cancer Center
Iwasaki, Motoki National Cancer Center|Jikei University School of Medicine
body mass index
colorectal cancer
Mendelian randomization
Content Type
Journal Article
Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.
Journal Title
Cancer Science
Japanese Cancer Association|John Wiley & Sons
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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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Medical Sciences