Type 2 diabetes and prostate cancer risk: a population-based case-control study in Montreal, Canada

Transcription

1 Type 2 diabetes and prostate cancer risk: a population-based case-control study in Montreal, Canada Audrey Blanc-Lapierre, Pierre I. Karakiewicz, Armen Aprikian, Fred Saad, Marie-Élise Parent June 2 nd 2015, 2015 CSEB Conference

2 Epidemiology of prostate cancer (PCa) Most common cancer in Canadian men 2 nd leading cause of cancer death among men in North America PCa risk PCa risk Established risk factors Age Black ancestry Family history of PCa Suspected risk factors Body fatness (for advanced PCa) Type 2 diabetes Limited evidence Unhealthy diet Physical activity 2

3 Type 2 diabetes (T2D) and PCa: an inverse relation Unlike many other cancers, PCa has been consistently observed to be inversely associated with T2D mrr: 0.86, 95% CI: Influence of T2D on PCa aggressiveness is still debated Ref: Bansal et al. 2013, Xu

4 T2D and PCa: unresolved issues Suggested mechanisms 1 Epidemiological evidence Variables of interest Under-detection of PCa among diabetics ( screening behavior, lower PSA levels) Limited data PCa screening history Genetic link between T2D and PCa insulin in long-standing T2D Metformin: direct or insulindependent anti-tumor effect Limited data Limited and conflicting data regarding insulin-related biomarkers or diabetes duration Limited and conflicting data 2 Family history of PCa Diabetes duration Metformin use 1 Pierce 2012, Rastmanesh 2014; 2 Franciosi

5 Objectives Suggested mechanisms 1 Epidemiological evidence Variables of interest To further investigate the relation between T2D Under-detection and PCa risk (and of PCa PCa aggressiveness) by among addressing: diabetics Limited data ( screening behavior, lower 4 PCa screening history PSA levels) Modification by Genetic link between T2D and PCa insulin in long-standing T2D Metformin: direct or insulindependent anti-tumor effect Limited data Limited and conflicting data regarding insulin-related biomarkers or diabetes duration Association with Limited and conflicting data 2 Family history of PCa Diabetes duration Metformin use 5

6 Methods: study population Cases (N =1937) Controls (N =1995) Histologically confirmed PCa No PCa diagnosis Newly diagnosed across 7 French hospitals in the Montreal area between 2005 and 2009 Canadian citizens, residents of the greater Montreal area Aged 75 at diagnosis Concurrently and randomly selected from the electoral list of French-speaking men Residents of the same electoral districts as cases Frequency-matched (±5 yrs) 6

7 Methods: data collection Data collected* Socio-demographic Anthropometrics Lifestyle factors Potential confounders Education, ancestry BMI Smoking, alcohol, diet, physical activity (home/leisure/work) Medical history 1 st degree family history of PCa PCa screening history Diabetes: age at diagnosis medications (start/stop ages, duration) *Face-to-face interviews 7

8 Methods: analyses Exposure variables Prevalence of T2D T2D duration (time since T2D diagnosis) Use of Metformin and other anti-diabetic medications Analyses Unconditional logistic models: risk for overall PCa Polytomous logistic models: risks for low-grade (Gleason scores 7 or 3+4) and high-grade (Gleason scores >7 or 4+3) PCa Analyses stratified by family history of PCa Analyses restricted to subjects recently screened for PCa 8

9 Results: population Cases Controls Mean age ±SD (yrs) 64 ±7 65 ±7 Black ancestry (%) 7 5 Family history of PCa (%) Last PCa screening 2 yrs (%) Daily freq. of use of fruit and vegetables ±SD 11 ±10 11 ±11 High physical activity (%) Mean BMI 2 yrs ago ±SD (kg/m 2 ) 26.8 ± ±4 Statins use (%) T2D 2 yrs ago (%)

10 ORs for the association between T2D and PCa Overall Low grade High grade OR (95%CI) Adjusted for age, education, BMI and ancestry Similar results in analyses restricted to subjects screened for PCa in the last 2 yrs 10

11 ORs for the association between T2D and PCa, according to a family history of PCa Overall Low grade High grade OR (95%CI) No Yes No Yes No Yes Family history of PCa 11

12 ORs for the association between T2D and PCa, according to T2D duration Overall Low grade High grade OR (95%CI) T2DM duration 12

13 ORs for the association between T2D and PCa, according to anti-diabetic medication use OR (95%CI) No change according to T2D duration Stronger association for low grade PCa 13

14 Discussion Suggested mechanisms Under-detection of PCa among diabetics Variables PCa screening history Negative association T2D PCa - Similar results among subjects recently screened - Similar biopsy rates among T2D and non T2D controls - Similar risks according to PCa aggressiveness 14

15 Discussion Suggested mechanisms Under-detection of PCa among diabetics Genetic link between T2D and PCa Variables PCa screening history Family history of PCa Negative association T2D PCa - Similar results among subjects recently screened - Similar biopsy rates among T2D and non T2D controls - Similar risks according to PCa aggressiveness Stronger among subjects with a family history of PCa (+++ high grade PCa) 15

16 Discussion Suggested mechanisms Under-detection of PCa among diabetics Genetic link between T2D and PCa insulin in longstanding T2D Variables PCa screening history Family history of PCa Diabetes duration Negative association T2D PCa - Similar results among subjects recently screened - Similar biopsy rates among T2D and non T2D controls - Similar risks according to PCa aggressiveness Stronger among subjects with a family history of PCa (+++ high grade PCa) Stronger with long-standing T2D (+++ low grade PCa) 16

17 Discussion Suggested mechanisms Under-detection of PCa among diabetics Genetic link between T2D and PCa insulin in longstanding T2D Metformin: direct or insulin-dependent antitumor effect Variables PCa screening history Family history of PCa Diabetes duration Metformin use Negative association T2D PCa - Similar results among subjects recently screened - Similar biopsy rates among T2D and non T2D controls - Similar risks according to PCa aggressiveness Stronger among subjects with a family history of PCa (+++ high grade PCa) Stronger with long-standing T2D (+++ low grade PCa) Stronger with use of Metformin (+++ low grade PCa) 17

18 Conclusion Our results support the hypothesis of an inverse relationship between diabetes and prostate cancer, possibly due to genetic, hormonal or pharmacological causes involved in different steps of the PCa development. 18

19 Thank you - All of you for your attention - My research supervisor, Marie-Élise Parent - Deborah Weiss (research assistant ) - Hugues Richard (biostatistician) - Marie-Claire Goulet (study s coordinator) - All other members of the Epidemiology & Biostatistics unit

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