双样本孟德尔随机化法分析糖尿病对前列腺癌症的影响

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Abstract Objective This study aims to address the uncertainty regarding the causal relationship between diabetes mellitus (DM) and prostate cancer. By employing Mendelian randomization, we can eliminate potential confounding factors and clarify the causal link between DM and prostate cancer, which will aid in the prevention and treatment of these two diseases in clinical practice. Methods We utilized data from genome-wide association studies (GWAS) focused on type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and prostate cancer, all based on European populations. The T1DM dataset comprised 3, 428 patients with diabetes and 3, 428 healthy controls. The T2DM dataset included 148, 726 patients with diabetes and 965, 732 healthy controls. The prostate cancer dataset included 30, 945 patients with prostate disease and 368, 725 healthy individuals as controls. T2DM was used as the exposure variable, and we identified significantly associated and independent single nucleotide polymorphism (SNP) as instrumental variables. We employed a two-sample Mendelian randomization (2SMR) approach to evaluate the causal relationship between T1DM, T2DM, and prostate cancer. The analysis incorporated five methods: inverse variance weighting (IVW), Mendelian randomization regression (MR-Egger), weighted median, weighted mode, and simple mode, with IVW serving as the primary analytical method. Cochran's Q statistic was utilized to assess heterogeneity. Results The findings indicate that no causal effect was observed between T1DM and prostate cancer (IVW: OR=0.99; 95% CI: 0.99-1.001, P=0.18). In contrast, the presence of T2DM is associated with an increased incidence of prostate cancer in the overall population (IVW: OR=7.88, 95% CI: 6.95-8.93, P<0.05). Conclusion There is a causal relationship between T2DM and prostate cancer, and T2DM increases the risk of developing prostate cancer. However, no promotive relationship was found between T1DM and prostate cancer.

Key words： Mendelian randomization diabetes prostate cancer

Received: 26 April 2024

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R737

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	WANG Jin
	ZOU Zhi
	LIU Bang
	NING Shuancheng
	CHEN Xiangyu

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WANG Jin,ZOU Zhi,LIU Bang等. Analysis of the Impact of Diabetes on Prostate Cancer Using Two-Sample Mendelian Randomization[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2024, 21(5): 24-30.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2024/V21/I5/24

[1] TINAJERO MG, MALIK VS.An Update on the Epidemiology of Type 2 Diabetes: A Global Perspective[J]. Endocrinol Metab Clin North Am, 2021, 50(3) : 337-355.
[2] LINDEMANN K, VATTEN LJ, ELLSTRØM-ENGH M, et al. Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study[J]. Br J Cancer, 2008, 98(9) : 1582-1585.
[3] BEN Q, XU M, NING X, et al.Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies[J]. Eur J Cancer, 2011, 47(13) : 1928-1937.
[4] YUHARA H, STEINMAUS C, COHEN SE, et al.Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer?[J]. Am J Gastroenterol, 2011, 106(11) : 1911-1921.
[5] KITAHARA CM, PLATZ EA, BEANE FREEMAN LE, et al.Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies[J]. Cancer Causes Control, 2012, 23(3) : 463-471.
[6] KASPER JS, LIU Y, GIOVANNUCCI E.Diabetes mellitus and risk of prostate cancer in the health professionals follow-up study[J]. Int J Cancer, 2009, 124(6) : 1398-1403.
[7] TSILIDIS KK, KASIMIS JC, LOPEZ DS, et al.Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies[J]. BMJ, 2015, 350: g7607.
[8] BONOVAS S, FILIOUSSI K, TSANTES A.Diabetes mellitus and risk of prostate cancer: a meta-analysis[J]. Diabetologia, 2004, 47(6) : 1071-1078.
[9] KASPER JS, GIOVANNUCCI E.A meta-analysis of diabetes mellitus and the risk of prostate cancer[J]. Cancer Epidemiol Biomarkers Prev, 2006, 15(11) : 2056-2062.
[10] JIAN GANG P, MO L, LU Y, et al.Diabetes mellitus and the risk of prostate cancer: an update and cumulative meta-analysis[J]. Endocr Res, 2015, 40(1) : 54-61.
[11] CAI H, XU Z, XU T, et al.Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: a meta-analysis of 11 cohort studies[J]. Diabetes Metab Res Rev, 2015, 31(4) : 336-343.
[12] FLANAGAN J, GRAY PK, HAHN N, et al.Presence of the metabolic syndrome is associated with shorter time to castration-resistant prostate cancer[J]. Ann Oncol, 2011, 22(4) : 801-807.
[13] RUDMAN SM, GRAY KP, BATISTA JL, et al.Risk of prostate cancer-specific death in men with baseline metabolic aberrations treated with androgen deprivation therapy for biochemical recurrence[J]. BJU Int, 2016, 118(6) : 919-926.
[14] ARSENAULT BJ.From the garden to the clinic: how Mendelian randomization is shaping up atherosclerotic cardiovascular disease prevention strategies[J]. Eur Heart J, 2022, 43(42) : 4447-4449.
[15] ZHENG J, HABERLAND V, BAIRD D, et al.Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases[J]. Nat Genet, 2020, 52(10) : 1122-1131.
[16] BURGESS S, DAVEY SMITH G, DAVIES NM, et al.Guidelines for performing Mendelian randomization investigations: update for summer 2023[J]. Wellcome Open Res, 2023, 4: 186.
[17] DE SILVA K, DEMMER RT, JÖNSSON D, et al. Causality of anthropometric markers associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study[J]. PLoS One, 2022, 17(6) : e0269191.
[18] BOWDEN J, DEL GRECO M F, MINELLI C, et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization[J]. Stat Med, 2017, 36(11) : 1783-1802.
[19] HEMANI G, TILLING K, DAVEY SMITH G.Orienting the causal relationship between imprecisely measured traits using GWAS summary data[J]. PLoS Genet, 2017, 13(11) : e1007081.
[20] PAPATHEODOROU K, BANACH M, BEKIARI E, et al.Complications of Diabetes 2017[J]. J Diabetes Res, 2018, 2018: 3086167.
[21] THOMAS JA 2ND, ANTONELLI JA, LLOYD JC, et al. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model[J]. Prostate Cancer Prostatic Dis, 2010, 13(4) : 350-355.
[22] XU H, JIANG HW, DING GX, et al.Diabetes mellitus and prostate cancer risk of different grade or stage: a systematic review and meta-analysis[J]. Diabetes Res Clin Pract, 2013, 99(3) : 241-249.
[23] ANTZA C, KOSTOPOULOS G, MOSTAFA S, et al.The links between sleep duration, obesity and type 2 diabetes mellitus[J]. J Endocrinol, 2021, 252(2) : 125-141.
[24] RASTMANESH R, HEJAZI J, MAROTTA F, et al.Type 2 diabetes: a protective factor for prostate cancer? An overview of proposed mechanisms[J]. Clin Genitourin Cancer, 2014, 12(3) : 143-148.
[25] WRIGHT JL, STANFORD JL.Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study[J]. Cancer Causes Control, 2009, 20(9) : 1617-1622.
[26] ZAKIKHANI M, DOWLING RJ, SONENBERG N, et al.The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase[J]. Cancer Prev Res (Phila) , 2008, 1(5) : 369-375.
[27] DOWLING RJ, ZAKIKHANI M, FANTUS IG, et al.Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells[J]. Cancer Res, 2007, 67(22) : 10804-10812.
[28] SCHNEIDER MB, MATSUZAKI H, HAORAH J, et al.Prevention of pancreatic cancer induction in hamsters by metformin[J]. Gastroenterology, 2001, 120(5) : 1263-1270.
[29] ALGIRE C, ZAKIKHANI M, BLOUIN MJ, et al.Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth[J]. Endocr Relat Cancer, 2008, 15(3) : 833-839.
[30] BUZZAI M, JONES RG, AMARAVADI RK, et al.Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth[J]. Cancer Res, 2007, 67(14) : 6745-6752.
[31] BIRNEY E.Mendelian Randomization[J]. Cold Spring Harb Perspect Med, 2022, 12(4) : a041302.
[32] MAAHS DM, WEST NA, LAWRENCE JM, et al.Epidemiology of type 1 diabetes[J]. Endocrinol Metab Clin North Am, 2010, 39(3) : 481-497.
[33] CLOETE L.Diabetes mellitus: an overview of the types, symptoms, complications and management[J]. Nurs Stand, 2022, 37(1) : 61-66.
[34] KWAK SH, PARK KS.Recent progress in genetic and epigenetic research on type 2 diabetes[J]. Exp Mol Med, 2016, 48(3) : e220.
[35] SANGHERA DK, ORTEGA L, HAN S, et al.Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala) , IGF2BP2, TCF7L2 and FTO variants confer a significant risk[J]. BMC Med Genet, 2008, 9: 59.