Background: Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors. The aims of this study were to determine if TCF7L2 rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status.
Methods: We prospectively followed 8,558 men in the Malmö Diet and Cancer Study from baseline 1991-1996 until end of 2009. Cox regression models were used to assess the association between rs7903146 T2D-risk allele (T) and PCa. Effect modification by incident T2D status, fasting glucose levels, dietary, and lifestyle risk factors were tested.
Results: During follow-up 855 incident PCa cases were registered. We observed a non-significant tendency for the TCF7L2 variant to associate with higher risk of PCa, which was unaffected by adjustment for incident T2D (HR = 1.24; 95% CI: 0.96, 1.60; P = 0.079) but more pronounced among subjects who developed T2D (HR = 1.91, 95% CI: 0.88, 4.14; P = 0.064). In a sub-sample of hyperglycemic men we observed an increased risk of PCa among T-allele carriers (HR = 2.72, 95% CI: 1.22, 6.04; P = 0.014; P(interaction) = 0.056). T-allele carriers with higher number of lifestyle risk factors had an increased risk of PCa (P(interaction) = 0.006).
Conclusions: We found no independent association between TCF7L2 rs7903146 and PCa risk. However, among hyperglycemic men we observed that the risk allele may increase risk of PCa. The association between rs7903146 and PCa risk may also be modified by lifestyle factors.
Keywords: cohort; diet; epidemiology; gene-environment interaction; genetic variation; lifestyle; prostate cancer; transcription factor 7-like 2; type 2 diabetes.
© 2014 Wiley Periodicals, Inc.