Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study).
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
18
04
2021
accepted:
18
08
2021
revised:
10
08
2021
pubmed:
4
10
2021
medline:
1
12
2022
entrez:
3
10
2021
Statut:
ppublish
Résumé
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. 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. Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (OR Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.
Sections du résumé
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 (OR
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.
Identifiants
pubmed: 34601492
doi: 10.1038/s41391-021-00446-w
pii: 10.1038/s41391-021-00446-w
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
694-699Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–53.
doi: 10.1002/ijc.31937
Plym A, Penney KL, Kalia S, Kraft P, Conti DV, Haiman C et al. Evaluation of a multiethnic polygenic risk score model for prostate cancer. J Natl Cancer Inst. 2021. https://doi.org/10.1093/jnci/djab058 . [Online ahead of print].
Dahut WL, Couvillon A, Pinto PA, Turkbey B, Karzai F. Natural history and imaging in men with high genetic risk for developing prostate cancer. Can J Urol. 2019;26:7–8.
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, et al. Familial risk and heritability of cancer among twins in nordic countries. JAMA. 2016;315:68–76.
doi: 10.1001/jama.2015.17703
Saunders EJ, Kote-Jarai Z, Eeles RA. Identification of germline genetic variants that increase prostate cancer risk and influence development of aggressive disease. Cancers. 2021;13:760.
doi: 10.3390/cancers13040760
World Cancer Research Fund International/American Institute for Cancer Research Continuous Update Project Report. Diet, Nutrition, Physical Activity, and Prostate Cancer. 2014. www.wcrf.org/sites/default/files/Prostate-Cancer-2014-Report.pdf .
Pilleron S, Sarfati D, Janssen-Heijnen M, Vignat J, Ferlay J, Bray F, et al. Global cancer incidence in older adults, 2012 and 2035: A population-based study. Int J Cancer. 2019;144:49–58.
doi: 10.1002/ijc.31664
Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol. 2014;65:1046–55.
doi: 10.1016/j.eururo.2013.12.062
Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Melnikow J. Prostate-specific antigen-based screening for prostate cancer: evidence report and systematic review for the US preventive services task force. JAMA. 2018;319:1914–31.
doi: 10.1001/jama.2018.3712
Sacerdote C, Ricceri F. Epidemiological dimensions of the association between type 2 diabetes and cancer: A review of observational studies. Diabetes Res Clin Pr. 2018;143:369–77.
doi: 10.1016/j.diabres.2018.03.002
Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16:151–8. S1
doi: 10.1038/pcan.2012.40
Tsilidis KK, Allen NE, Appleby PN, Rohrmann S, Nöthlings U, Arriola L, et al. Diabetes mellitus and risk of prostate cancer in the European prospective investigation into cancer and nutrition. Int J Cancer. 2015;136:372–81.
doi: 10.1002/ijc.28989
Häggström C, Van Hemelrijck M, Zethelius B, Robinson D, Grundmark B, Holmberg L, et al. Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer. Int J Cancer. 2017;140:611–7.
doi: 10.1002/ijc.30480
Xu H, Jiang H, Ding G, Zhang H, Zhang L, Mao S, et al. Diabetes mellitus and prostate cancer risk of different grade or stage: a systematic review and meta-analysis. Diabetes Res Clin Pr. 2013;99:241–9.
doi: 10.1016/j.diabres.2012.12.003
Chen M, Luo Y, Yang S, Xu L, Li N, Li H, et al. Association of diabetes mellitus with prostate cancer grade and prostate-specific antigen in Chinese biopsy population. Diabetes Res Clin Pr. 2018;141:80–87.
doi: 10.1016/j.diabres.2018.04.022
Dankner R, Boffetta P, Keinan-Boker L, Balicer RD, Berlin A, Olmer L, et al. Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men. Diabetologia. 2016;59:1683–91.
doi: 10.1007/s00125-016-3972-x
Miller EA, Pinsky PF, Pierre-Victor D. The relationship between diabetes, prostate-specific antigen screening tests, and prostate cancer. Cancer Causes Control. 2018;29:907–14.
doi: 10.1007/s10552-018-1067-3
Feng X, Song M, Preston MA, Ma W, Hu Y, Pernar CH, et al. The association of diabetes with risk of prostate cancer defined by clinical and molecular features. Br J Cancer. 2020;123:657–65.
doi: 10.1038/s41416-020-0910-y
Lin E, Garmo H, Van Hemelrijck M, Adolfsson J, Stattin P, Zethelius B, et al. Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study. BMC Cancer. 2020;20:551.
doi: 10.1186/s12885-020-07036-4
Ballotari P, Vicentini M, Manicardi V, Gallo M, Chiatamone Ranieri S, Greci M, et al. Diabetes and risk of cancer incidence: results from a population-based cohort study in northern Italy. BMC Cancer. 2017;17:703.
doi: 10.1186/s12885-017-3696-4
Lind M, Fahlén M, Eliasson B, Odén A. The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes. Prim Care Diabetes. 2012;6:53–59.
doi: 10.1016/j.pcd.2011.10.004
Zaidi S, Gandhi J, Joshi G, Smith NL, Khan SA. The anticancer potential of metformin on prostate cancer. Prostate Cancer Prostatic Dis. 2019;22:351–61.
doi: 10.1038/s41391-018-0085-2
Kincius M, Patasius A, Linkeviciute-Ulinskiene D, Zabuliene L, Smailyte G. Reduced risk of prostate cancer in a cohort of Lithuanian diabetes mellitus patients. Aging Male. 2020;23:1333–8.
doi: 10.1080/13685538.2020.1766013
Castaño-Vinyals G, Aragonés N, Pérez-Gómez B, Martín V, Llorca J, Moreno V, et al. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design. Gac Sanit. 2015;29:308–15.
doi: 10.1016/j.gaceta.2014.12.003
World Health Organization. Anatomical Therapeutic Chemical (ATC) Classification. Accessed 8 January 2021. https://www.who.int/tools/atc-ddd-toolkit/atc-classification .
Egevad L, Delahunt B, Srigley JR, Samaratunga H. International Society of Urological Pathology (ISUP) grading of prostate cancer - An ISUP consensus on contemporary grading. APMIS. 2016;124:433–5.
doi: 10.1111/apm.12533
Gómez-Acebo I, Dierssen-Sotos T, Fernandez-Navarro P, Palazuelos C, Moreno V, Aragonés N, et al. Risk model for prostate cancer using environmental and genetic factors in the Spanish multi-case-control (MCC) study. Sci Rep. 2017;7:8994.
doi: 10.1038/s41598-017-09386-9
Rastmanesh R, Hejazi J, Marotta F, Hara N. Type 2 diabetes: a protective factor for prostate cancer? An overview of proposed mechanisms. Clin Genitourin Cancer. 2014;12:143–8.
doi: 10.1016/j.clgc.2014.01.001
Elabbady A, Hashad MM, Kotb AF, Ghanem AE. Studying the effect of type 2 diabetes mellitus on prostate-related parameters: a prospective single institutional study. Prostate Int. 2016;4:156–9.
doi: 10.1016/j.prnil.2016.07.005
Pashayan N, Pharoah PD, Schleutker J, Talala K, Tammela TL, Määttänen L, et al. Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC. Br J Cancer. 2015;113:1086–93.
doi: 10.1038/bjc.2015.289
Sipeky C, Talala KM, Tammela TLJ, Taari K, Auvinen A, Schleutker J. Prostate cancer risk prediction using a polygenic risk score. Sci Rep. 2020;10:17075.
doi: 10.1038/s41598-020-74172-z
Xiang YZ, Jiang SB, Zhao J, Xiong H, Cui ZL, Li GB, et al. Racial disparities in the association between diabetes mellitus-associated polymorphic locus rs4430796 of the HNF1β gene and prostate cancer: a systematic review and meta-analysis. Genet Mol Res. 2014;13:6582–92.
doi: 10.4238/2014.August.28.3
Machiela MJ, Lindström S, Allen NE, Haiman CA, Albanes D, Barricarte A, et al. Association of type 2 diabetes susceptibility variants with advanced prostate cancer risk in the Breast and Prostate Cancer Cohort Consortium. Am J Epidemiol. 2012;176:1121–9.
doi: 10.1093/aje/kws191
Pierce BL, Ahsan H. Genetic susceptibility to type 2 diabetes is associated with reduced prostate cancer risk. Hum Hered. 2010;69:193–201.
doi: 10.1159/000289594
Frayling TM, Colhoun H, Florez JC. A genetic link between type 2 diabetes and prostate cancer. Diabetologia. 2008;51:1757–60.
doi: 10.1007/s00125-008-1114-9
Cuyàs E, Verdura S, Llorach‐Pares L, Fernández‐Arroyo S, Luciano‐Mateo F, Cabré N, et al. Metformin directly targets the H3K27me3 demethylase KDM6A/UTX. Aging Cell. 2018;17:e12772.
doi: 10.1111/acel.12772
Wang Y, Liu X, Yan P, Tang J, Chen T, Sun Y, et al. Effect of metformin on the risk of prostate cancer in patients with type 2 diabetes by considering different confounding factors: a meta-analysis of observational studies. Eur J Cancer Prev. 2020;29:42–52.
doi: 10.1097/CEJ.0000000000000514
Ghiasi B, Sarokhani D, Najafi F, Motedayen M, Dehkordi AH. The relationship between prostate cancer and metformin consumption: a systematic review and meta-analysis study. Curr Pharm Des. 2019;25:1021–9.
doi: 10.2174/1381612825666190215123759
He K, Hu H, Ye S, Wang H, Cui R, Yi L. The effect of metformin therapy on incidence and prognosis in prostate cancer: A systematic review and meta-analysis. Sci Rep. 2019;9:2218.
doi: 10.1038/s41598-018-38285-w
Chien S-W, Kuo D-Y, Liao J-M, Wang PS, Yu C-H. Growth modulation of diabetic factors and antidiabetic drugs on prostate cancer cell lines. Chin J Physiol. 2016;59:109–18.
Chen Y, Chen Q, Wang Z, Zhou J. Insulin therapy and risk of prostate cancer: a systematic review and meta-analysis of observational studies. PLoS ONE. 2013;8:e81594.
doi: 10.1371/journal.pone.0081594
Colmers IN, Bowker SL, Tjosvold LA, Johnson JA. Insulin use and cancer risk in patients with type 2 diabetes: a systematic review and meta-analysis of observational studies. Diabetes Metab. 2012;38:485–506.
doi: 10.1016/j.diabet.2012.08.011
Cambra K, Galbete A, Forga L, Lecea O, Ariz MJ, Moreno-Iribas C, et al. Sex and age differences in the achievement of control targets in patients with type 2 diabetes: results from a population-based study in a South European region. BMC Fam Pract. 2016;17:144.
doi: 10.1186/s12875-016-0533-9
Basterra-Gortari FJ, Bes-Rastrollo M, Ruiz-Canela M, Gea A, Martinez-Gonzalez MÁ. Prevalencia de obesidad y diabetes en adultos españoles, 1987-2012. Med Clínica. 2017;148:250–6.
doi: 10.1016/j.medcli.2016.11.022
International Diabetes Federation. IDF Diabetes Atlas. 9th edn. International Diabetes Federation: Brussels, Belgium, 2019. https://www.diabetesatlas.org .