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Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data

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Abstract

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.

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Acknowledgments

This work was supported by Department of Defense grant W81XWH-10-1-0499 (to BLP) and NIH grants CA122171 and CA102484 (to HA). The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Health Studies and Comprehensive Cancer Center, The University of Chicago, 5841 South Maryland Avenue, Suite N101, Chicago, IL, 60637, USA

    Brandon L. Pierce

  2. Institute for Public Health Genetics and Department of Epidemiology, University of Washington, Seattle, WA, 98195, USA

    Melissa A. Austin

  3. Center for Cancer Epidemiology and Prevention, Department of Health Studies, The University of Chicago, 5841 South Maryland Avenue, Suite N101, Chicago, IL, 60637, USA

    Habibul Ahsan

  4. Departments of Medicine and Human Genetics and Comprehensive Cancer Center, The University of Chicago, Chicago, IL, 60637, USA

    Habibul Ahsan

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  1. Brandon L. Pierce
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  2. Melissa A. Austin
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Correspondence to Brandon L. Pierce.

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Pierce, B.L., Austin, M.A. & Ahsan, H. Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data. Cancer Causes Control 22, 877–883 (2011). https://doi.org/10.1007/s10552-011-9760-5

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  • DOI: https://doi.org/10.1007/s10552-011-9760-5

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