Fat mass and obesity-associated gene polymorphisms, pre-diagnostic plasma adipokine levels and the risk of colorectal cancer: The Japan Public Health Center-based Prospective Study

PLoS One. 2020 Feb 13;15(2):e0229005. doi: 10.1371/journal.pone.0229005. eCollection 2020.


Although their functional outcomes remain largely unknown, single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated gene (FTO) may interact with adipokines, especially leptin and adiponectin, to modify the risk of colorectal cancer. We conducted a prospective study of 375 colorectal cancer cases and 750 matched controls to examine the effects of SNPs in the FTO, either alone or in interaction with pre-diagnostic plasma adipokine levels. Using a conditional logistic regression model, we obtained odds ratios (ORs) and their 95% confidence intervals (CIs) of colorectal cancer. Seven SNPs in strong linkage disequilibrium demonstrated a similarly positive association with colorectal cancer, and most evidently for rs1558902, rs8050136, rs3751812, and rs9939609 (Ptrend = 0.02). Of interest, we observed a statistically significant interaction of rs8050136 with plasma total adiponectin levels (Pinteraction = 0.03). Compared to non-carriers in the lowest quintile of plasma total adiponectin, A allele carriers in the same quintile showed a considerably elevated risk of colorectal cancer, with a body mass index-adjusted OR of 2.54 (95% CI, 1.36-4.75). This investigation of the interaction between SNPs in the FTO and pre-diagnostic plasma adipokine levels has revealed the importance of both genetic and hormonal factors associated with adiposity in colorectal carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood*
  • Adult
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Colorectal Neoplasms / blood*
  • Confidence Intervals
  • Female
  • Genome-Wide Association Study / methods
  • Humans
  • Linkage Disequilibrium / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*


  • Adipokines
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grants and funding

This study was supported by a National Cancer Center Research and Development Fund from the Ministry of Health, Labour and Welfare of Japan to S.T. (23-A-31[toku], 26-A-2 and 29-A-4 since 2011) and to M.I (25-A-14 from 2013 to 2015), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan to S.T. (from 1989 to 2010), Funds for integrated promotion of social system reform and research and development from the Japan Science and Technology Agency to S.T. (37201101-01 from 2011 to 2013), and a Grant-in-Aid for Scientific Research C from the Japan Society for the Promotion of Science to T.Y. (15K08722 since 2015 to 2017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.