TCF7L2 type 2 diabetes risk variant, lifestyle factors, and incidence of prostate cancer. Issue 12 (24th June 2014)

• Record Type: Journal Article
• Authors: Drake, Isabel; Wallström, Peter; Hindy, George; Ericson, Ulrika; Gullberg, Bo; Bjartell, Anders; Sonestedt, Emily; Orho‐Melander, Marju; Wirfält, Elisabet
• Is Part Of: Prostate. Volume 74:Issue 12(2014)
• Page Start: 1161
• Page End: 1170
• Publication Date: 2014-06-24
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22832
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22832-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Variation in transcription factor 7‐like 2 (<italic>TCF7L2</italic>), 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 <italic>TCF7L2</italic> rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status.</p> </sec> <sec id="pros22832-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="pros22832-sec-0003" sec-type="section"> <title>RESULTS</title> <p>During follow‐up 855 incident PCa cases were registered. We observed a non‐significant tendency for the <italic>TCF7L2</italic> 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; <italic>P</italic> = 0.079) but more pronounced among subjects who developed T2D (HR = 1.91, 95% CI: 0.88, 4.14; <italic>P</italic> = 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; <italic>P</italic> = 0.014; <italic>P</italic><sub>interaction</sub> = 0.056). T‐allele carriers with higher number of lifestyle risk factors had an increased risk of PCa (<italic>P</italic><sub>interaction</sub> = 0.006).</p> </sec> <sec id="pros22832-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>We found no independent association between <italic>TCF7L2</italic> 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. <italic>Prostate 74:1161–1170, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>