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Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)

Abstract: Background: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.

 Authorship: Barrios-Rodríguez R., García-Esquinas E., Pérez-Gómez B., Castaño-Vinyals G., Llorca J., de Larrea-Baz N.F., Olmedo-Requena R., Vanaclocha-Espi M., Alguacil J., Fernández-Tardón G., Fernández-Navarro P., Cecchini L., Lope V., Gómez-Acebo I., Aragonés N., Kogevinas M., Pollán M., Jiménez-Moleón J.J.,

 Fuente: Prostate Cancer Prostatic Dis . 2022 Apr;25(4):694-699

 Publisher: Springer Nature

 Year of publication: 2022

 No. of pages: 6

 Publication type: Article

 DOI: 10.1038/s41391-021-00446-w

 ISSN: 1365-7852,1476-5608

 Publication Url: https://doi.org/10.1038/s41391-021-00446-w

Authorship

BARRIOS-RODRÍGUEZ, ROCÍO

GARCÍA-ESQUINAS, ESTHER

PÉREZ-GÓMEZ, BEATRIZ

CASTAÑO-VINYALS, GEMMA

FRANCISCO JAVIER LLORCA DIAZ

DE LARREA-BAZ, NEREA FERNÁNDEZ

OLMEDO-REQUENA, ROCÍO

VANACLOCHA-ESPI, MERCEDES

ALGUACIL, JUAN

FERNÁNDEZ-TARDÓN, GUILLERMO

FERNÁNDEZ-NAVARRO, PABLO

CECCHINI, LLUÍS

LOPE, VIRGINIA

ARAGONÉS, NURIA

KOGEVINAS, MANOLIS

POLLÁN, MARINA

JIMÉNEZ-MOLEÓN, JOSÉ JUAN