title: Association between markers of glucose metabolism and risk of colorectal cancer.
abstract: Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach.
  
  
  
  Systematic review and meta-analysis.
  
  
  
  PubMed and EMBASE were searched up to May 2015.
  
  
  
  Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose-response, meta-regression, subgroup and publication bias analyses were conducted.
  
  
  
  35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case-control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer.
  
  
  
  The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case-control studies in the current analysis, more cohort studies are warranted to enhance future analysis.
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Xu
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, USA.
authors.forename: Penelope
authors.initials: P
authors.lastname: Duerksen-Hughes
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Honghe
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Peiwei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Zhejiang University School of Public Health, Hangzhou, China Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Dajing
authors.initials: D
authors.lastname: Xia
mesh_terms: D015415:Biomarkers; D002096:C-Peptide / Q000097:blood*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D005947:Glucose; D006442:Glycated Hemoglobin
keywords: C-peptide; HOMA-IR; HbA1c; colorectal cancer; fasting glucose; fasting insulin