Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data.
Summary of "Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data."
OBJECTIVE:
To examine associations between recently identified common type 2 diabetes (T2D) susceptibility genetic variants and pancreatic cancer risk.
METHODS:
Using data on individuals of European ancestry from the Cancer Genetic Markers of Susceptibility PanScan-I study (1,763 pancreatic cancer cases and 1,802 controls), we tested associations for 37 T2D susceptibility variants with pancreatic cancer risk. Associations with pancreatic cancer were also tested for three composite T2D susceptibility measures, incorporating data on all 37 variants, and for ten additional variants related to T2D-related phenotypes, including fasting glucose and beta-cell function.
RESULTS:
Of the 37 T2D risk alleles, two showed nominally significant positive associations with pancreatic cancer risk (FTO rs8050136 per-allele OR = 1.12;
CI:
1.02-1.23; MTNR1B rs1387153 OR = 1.11;
CI:
1.00-1.23) and one showed an inverse association (BCL11A rs243021 OR = 0.88;
CI:
0.80-0.97). The composite T2D susceptibility measures were not associated with pancreatic cancer. The glucose-raising allele of MADD rs11039149 was associated with increased risk of pancreatic cancer (OR = 1.14;
CI:
1.03-1.27).
CONCLUSIONS:
Overall, these results do not provide strong evidence that common variants underling T2D or related phenotypes also affect pancreatic cancer risk; however, associations for FTO, MTNR1B, BCL11A, and MADD variants warrant further investigation in larger studies. Hypothesis-driven analyses of existing genome-wide genetic data can be cost-efficient and promising approaches for investigating genetic susceptibility to complex diseases.
Affiliation
Department of Health Studies and Comprehensive Cancer Center, The University of Chicago, 5841 South Maryland Avenue, Suite N101, Chicago, IL, 60637, USA, brandonpierce@uchicago.edu.
Journal Details
This article was published in the following journal.
Name: Cancer causes & control : CCC
ISSN: 1573-7225
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21445555
- DOI: http://dx.doi.org/10.1007/s10552-011-9760-5
Medical and Biotech [MESH] Definitions
Prediabetic State
The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Metabolic Syndrome X
A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
Hyperlipoproteinemia Type V
A severe type of hyperlipidemia, sometimes familial, that it is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .
Polyuria
Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).
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