title: Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies.
abstract: 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
  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
  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 (P(trend)=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.
  
  
  CONCLUSIONS
  The findings suggest that diabetes risk variants also influence colorectal cancer susceptibility, possibly through mechanisms different from those for diabetes.
authors: Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96817, USA. icheng@crch.hawaii.edu
authors: Iona
authors: I
authors: Cheng
authors: Christian P
authors: CP
authors: Caberto
authors: Annette
authors: A
authors: Lum-Jones
authors: Ann
authors: A
authors: Seifried
authors: Lynne R
authors: LR
authors: Wilkens
authors: Fredrick R
authors: FR
authors: Schumacher
authors: Kristine R
authors: KR
authors: Monroe
authors: Unhee
authors: U
authors: Lim
authors: Maarit
authors: M
authors: Tiirikainen
authors: Laurence N
authors: LN
authors: Kolonel
authors: Brian E
authors: BE
authors: Henderson
authors: Daniel O
authors: DO
authors: Stram
authors: Christopher A
authors: CA
authors: Haiman
authors: Loïc
authors: L
authors: Le Marchand
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