Lifestyle factors that worsen glycaemic control have been hypothesized to contribute to cancer progression and compromise the effectiveness of treatment [1-5]. Based on previous in vitro studies, it was found that in high glucose conditions, breast and prostate cancer cells were more resistant to chemotherapy and this was via the increased expression of IGFBP-2 and down-regulation of PTEN levels ([6, 7] and unpublished data). Further research is needed to understand the mechanisms underlying the association between hyperglycaemia, cancer progression and the development of chemoresistance.
This proposal is for a Recall by Genotype study using genome-wide genotypic risk score for circulating glucose. With Dr Robert Scott (collaborator), we have developed a genome-wide genotypic risk score for circulating glucose that explains ~5% of observed variance in glucose levels (p =6.4x10-32). Recall of individuals based on the upper and lower tails of the genotypic risk score for glucose will enable the assessment of the biological implications of genetically randomised hyperglycaemia in humans and to enable further detailed and precise phenotyping.

References:
1. Hammarsten, J. and B. Hogstedt, Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer, 2005. 41(18): p. 2887-95.
2. Hammarsten, J. and B. Hogstedt, Clinical, haemodynamic, anthropometric, metabolic and insulin profile of men with high-stage and high-grade clinical prostate cancer. Blood Press, 2004. 13(1): p. 47-55.
3. Chen, Z., W. Lu, C. Garcia-Prieto and P. Huang, The Warburg effect and its cancer therapeutic implications. J Bioenerg Biomembr, 2007. 39(3): p. 267-74.
4. Yu, O.H., W.D. Foulkes, Z. Dastani, R.M. Martin, R. Eeles, P. Consortium, C.G. Investigators and J.B. Richards, An assessment of the shared allelic architecture between type II diabetes and prostate cancer. Cancer Epidemiol Biomarkers Prev, 2013. 22(8): p. 1473-5.
5. Pierce, B.L. and H. Ahsan, Genetic susceptibility to type 2 diabetes is associated with reduced prostate cancer risk. Hum Hered, 2010. 69(3): p. 193-201.
6. Biernacka, K.M., C.C. Uzoh, L. Zeng, R.A. Persad, A. Bahl, D. Gillatt, C.M. Perks and J.M. Holly, Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2. Endocr Relat Cancer, 2013. 20(5): p. 741-51.
7. Uzoh, C.C., J.M. Holly, K.M. Biernacka, R.A. Persad, A. Bahl, D. Gillatt and C.M. Perks, Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel. Br J Cancer, 2011. 104(10): p. 1587-93.