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Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies
  1. Iona Cheng1,
  2. Christian P Caberto1,
  3. Annette Lum-Jones1,
  4. Ann Seifried1,
  5. Lynne R Wilkens1,
  6. Fredrick R Schumacher2,
  7. Kristine R Monroe2,
  8. Unhee Lim1,
  9. Maarit Tiirikainen1,
  10. Laurence N Kolonel1,
  11. Brian E Henderson2,
  12. Daniel O Stram2,
  13. Christopher A Haiman2,
  14. Loïc Le Marchand1
  1. 1Epidemiology Program, University of Hawai'i Cancer Center, University of Hawai'i, Honolulu, Hawaii, USA
  2. 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  1. Correspondence to Iona Cheng, University of Hawaii Cancer Center, 1236 Lauhala Street, Suite 407, Honolulu, HI 96817, USA; icheng{at}crch.hawaii.edu

Abstract

Background

Background Diabetes has been positively associated with the risk of colorectal cancer. This study investigated whether recently established risk variants for diabetes also have effects on colorectal cancer.

Methods

Methods 19 single nucleotide repeats (SNPs) associated with type 2 diabetes in genome-wide association studies were tested in a case–control study of 2011 colorectal cancer cases and 6049 controls nested in the Multiethnic Cohort study as part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative. ORs and 95% CIs were estimated by unconditional logistic regression to evaluate the association between SNPs and colorectal cancer risk, adjusting for age, sex and race/ethnicity. Permutation testing was conducted to correct for multiple hypothesis testing.

Results

Results Four type 2 diabetes SNPs were associated with colorectal cancer risk: rs7578597 (THADA), rs864745 (JAZF1), rs5219 (KCNJ11) and rs7961581 (TSPAN8, LGR5). The strongest association was for the rs7578597 (THADA) Thr1187Ala missense polymorphism (Ptrend=0.004 adjusted for multiple testing), with the high risk allele for colorectal cancer being the low risk allele for diabetes. Similar patterns of associations were seen with further adjustment for diabetes status and body mass index. The association of diabetes status with colorectal cancer risk was somewhat weakened after adjustment for these SNPs.

Conclusion

Conclusion The findings suggest that diabetes risk variants also influence colorectal cancer susceptibility, possibly through mechanisms different from those for diabetes.

  • Colorectal cancer
  • SNPs
  • type 2 diabetes
  • genetic polymorphisms

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Footnotes

  • Funding NIH.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University of Hawaii and the University of Southern California.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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