|Year : 2018 | Volume
| Issue : 1 | Page : 24-31
A study of prostate cancer and its association with dyslipidemia, elevated insulin levels in blood, and relative insulin resistance prevalent in South East Asia
Poonam Kachhawa1, Kamal Kachhawa2, Divya Agrawal3, Vivek Sinha1, Purnima Dey Sarkar4, Sanjay Kumar5
1 Department of Biochemistry, Saraswathi Institute of Medical Sciences, Hapur, Uttar Pradesh, India
2 Department of Biochemistry, MIMS, Bhopal, India
3 Department of Anatomy, GSL Medical College, Rajahmundry, Andhra Pradesh, India
4 Department of Biochemistry, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh, India
5 Department of Pharmacology, GSL Medical College, Rajahmundry, Andhra Pradesh, India
|Date of Web Publication||26-Mar-2018|
Dr. Sanjay Kumar
Department of Pharmacology, GSL Medical College and Hospital, Rajahmundry - 533 296, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background and Objectives: Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide. In India, it is the second most common cancer in males as per the Indian Council of Medical Research and various state cancer registries. This study was designed to investigate the effect of dyslipidemia, elevated insulin levels, and insulin resistance on the risk of prostate cancer. Materials and Methods: This case–control study was conducted on a total of 200 individuals. Cases were 100 males under the age of 80 (range, 50–80 years), newly diagnosed with histologically confirmed primary adenocarcinoma of the prostate. Controls were 100 age-matched disease-free males, without any complications. Mean ± standard deviation in case and control groups was compared using the unpaired Student's t-test. Pearson's correlation analysis was used to determine the association between variables of interest and prostate-specific antigen (PSA), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), and body mass index (BMI) among prostate cancer patients. Unadjusted and adjusted odd ratios with 95% CI were calculated using logistic regression models for prostate cancer risk in relation to dyslipidemia and IR. Results: Data showed that serum PSA significantly positively associated with BMI, total cholesterol, triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), insulin, HOMA-IR and significantly negatively associated with high-density lipoprotein-cholesterol (HDL-C). HOMA-IR significantly positively associated with BMI, TGs, glucose, and insulin. The binary logistic regression analysis showed a significant adjusted* Odds Ratio (OR) with 95% confidence interval (P < 0.001) between total cholesterol (5.27 [1.87–14.8]), HDL-C (1.73 [1.02–3.42]), TGs (1.24 [1.05–1.37]), HOMA-IR (2.68 [1.53–4.62]), and prostate cancer. Conclusion: This study confirms the association between dyslipidemia, IR, and increased prostate cancer risk.
Keywords: Dyslipidemia, Homeostasis Model Assessment-Insulin Resistance, prostate cancer
|How to cite this article:|
Kachhawa P, Kachhawa K, Agrawal D, Sinha V, Sarkar PD, Kumar S. A study of prostate cancer and its association with dyslipidemia, elevated insulin levels in blood, and relative insulin resistance prevalent in South East Asia. J Integr Nephrol Androl 2018;5:24-31
|How to cite this URL:|
Kachhawa P, Kachhawa K, Agrawal D, Sinha V, Sarkar PD, Kumar S. A study of prostate cancer and its association with dyslipidemia, elevated insulin levels in blood, and relative insulin resistance prevalent in South East Asia. J Integr Nephrol Androl [serial online] 2018 [cited 2019 Aug 20];5:24-31. Available from: http://www.journal-ina.com/text.asp?2018/5/1/24/228496
| Introduction|| |
Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide. In India, it is the second most common cancer in males as per the Indian Council of Medical Research and various state cancer registries. The incidence rate in India is 9–10/100,000 population which is higher than other parts of Asia and Africa but lower than the USA and Europe. Incidence rates of this cancer are constantly and rapidly increasing in all the Population Based Cancer Registries.
An increasing number of studies suggest a role for lipid and glucose metabolism in prostate cancer development. Findings from a recent meta-analysis reported a strong positive association between obesity and the risk of advanced prostate cancer, indicating that lifestyle-related risk factors influence prostate cancer aggressiveness and progression. Nonetheless, epidemiological evidence on the association between other lifestyle-related risk factors, including dyslipidemia, diabetes and insulin resistance (IR), and prostate cancer development and progression, remains sparse and inconclusive.,,, Moreover, most of these studies are limited by few cases, short follow-up time, and lack of power to detect the true associations between the exposures and the outcomes. Biologically, both dyslipidemia and hyperglycemia have been implicated with prostate carcinogenesis. Evidence from experimental studies using in vivo and in vitro models demonstrated that they may induce prostate carcinogenesis by modulating signaling pathways, which promote carcinogenic processes such as cell growth and proliferation, inflammation, oxidative stress, and cell migration.,,,, Elevated serum glucose leads to rapid increment of insulin from the pancreatic beta cells, and high insulin levels can be associated with IR. In addition, insulin has potent mitogenic and growth-stimulatory effects on the prostate and other tissues, and alterations in these effects could potentially contribute to the development of malignancy. Therefore, among the pathophysiological entities that comprise metabolic syndrome, glucose, serum insulin, and IR may link to the risk of prostate cancer.
Previously, we provided evidence supporting a relationship of dyslipidemia, IR, and prostate-specific antigen (PSA) with prostate cancer. Our findings showed a positive correlation between serum PSA and total cholesterol, low-density lipoprotein-cholesterol (LDL-C), serum insulin, and IR. Conversely, we found that high-density lipoprotein-cholesterol (HDL-C) was inversely correlated with serum PSA. In this study, we increased some number of participants and we further investigated the effect of dyslipidemia, elevated insulin, and IR on the risk of prostate cancer. For risk study, we calculated crude and adjusted odd ratios.
| Materials and Methods|| |
This case–control study was conducted on a total of 200 individuals. Cases were 100 males under the age of 80 (range, 50–80 years), newly diagnosed with histologically confirmed primary adenocarcinoma of the prostate between 2013 and 2016 at our institution. Controls were 100 age-matched disease-free males, without any complications.
Specimen and laboratory assays
About 8 ml blood sample was withdrawn from the antecubital vein following overnight fasting. Serum was separated from the clotted blood by centrifugation for 15 min at 3000 rpm at room temperature. All serum samples were stored at −80°C until use. Glucose was measured enzymatically with a glucose oxidase and peroxidase method. Total cholesterol, HDL-C, and triglycerides (TGs) were also measured enzymatically using commercially available autoanalyzer kit. Very low-density lipoprotein-cholesterol (VLDL-C) and LDL-C were calculated by Friedwald's formula. All biochemical investigations were done by fully automated Turbo cam 100 analyzer (CPC diagnostics Pvt., Ltd., Alwarpet, Chennai, Tamil Nadu, India). The serum insulin (normal value <10 μlU/mL) done by ELISA is a solid-phase two-site enzyme immunoassay. IS130D (96 tests). The serum PSA done by sandwich ELISA technique is a solid phase assay based on streptavidin-biotin principle which was estimated by Calbiotech, Inc., PSA ELISA Kit and catalogue number PS235T (96 tests). The serum PSA normal value is <4 ng/mL. All assays were performed according to the respective manufacturer's instructions. Homeostasis Model Assessment-IR index (HOMAIR) which is used to define IR is calculated as follows: “fasting glucose (mg/dl) × fasting insulin (μlU/mL)/405,” the cutoff point was 2.5 or greater. Body mass index (BMI) was calculated as “weight in kilograms divided by height in meters squared (kg/m 2).”
The exclusion criteria included individuals with a diagnosis of any cancer other than primary prostate cancer and those who are suffering from diabetes, chronic liver disease, chronic renal disease, heart disease and those taking medications that influence blood glucose, serum lipid profile, and serum insulin.
Statistical analysis was performed using SPSS version 21.0 (IBM corporation, SPSS inc. RM 1804, Quarry Bay, Hongkong). Results are presented as mean ± standard deviation in case and control groups and compared using the unpaired Student's t-test. Pearson's correlation analysis was used to determine association between variables of interest and PSA, HOMA-IR, and BMI among prostate cancer patients. Unadjusted odds ratios (OR) with confidence intervals (CI) and adjusted * OR (95% CI) were calculated using logistic regression models for prostate cancer risk in relation to dyslipidemia and IR. In univariate analysis, variables statistically significant with prostate cancer risk (P< 0.10) were included in the multivariate logistic regression model. Multivariate models were adjusted by all variables in the models. The logistic regression analysis was done using the presence of prostate cancer as dependent variable and parameters of interest such as age, BMI, total cholesterol, TGs, HDL-C, glucose, serum insulin, and HOMAIR as independent variables. P < 0.05 was considered statistically significant.
The study was approved by the Ethical Committee of the Institute. An informed consent was obtained from each patient.
| Results|| |
[Table 1] highlights the clinical characteristics of prostate cancer cases and healthy controls in the study. The mean age of cases was 65.86 years and that of controls was 65.2 years. Data revealed that prostate cancer cases had significantly higher (P< 0.001) BMI, glucose, total cholesterol, TGs, LDL-C, VLDL-C, serum insulin, HOMA-IR, and serum PSA level compared to controls. HDL-C significantly decreased (P< 0.001) in prostate cancer patients as compared to controls [Figure 1]. There was no significant difference in age between cases and controls.
|Table 1: Comparison of biochemical parameters between prostate cancer cases and controls|
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|Figure 1: Biochemical parameters between prostate cancer cases and controls. FBS: Fasting Blood Sugar. TC: Total Cholesterol. HDL-C: High Density LipoproteinCholesterol. LDL-C: Low density Lipoprotein cholesterol. TAG: Triglyceride. VLDL-C: Very low density Lipoprotein cholesterol|
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[Table 2] shows Pearson's correlation analysis between variables of interest and PSA, HOMA-IR, and BMI among prostate cancer patients. Data showed that serum PSA significantly positively associated with BMI (r = 0.76), total cholesterol (r = 0.43) [Figure 2], TGs (r = 0.27), LDL-C (r = 0.48), insulin (r = 0.29), and HOMA-IR (r = 0.30) [Figure 3] and significantly negatively associated with HDL-C (r = −0.55) [Figure 4]. PSA was not correlated with age and glucose. HOMA-IR significantly positively associated with BMI (r = 0.57), TGs (r = 0.27), glucose (r = 0.76) [Figure 5], and insulin (r = 0.98) and was not correlated with age, total cholesterol, HDL-C, and LDL-C. BMI significantly positively associated with total cholesterol (r = 0.57), TGs (r = 0.40), LDL-C (r = 0.61), glucose (r = 0.43), insulin (r = 0.56) and significantly negatively associated with HDL-C (r = −0.64).
|Table 2: Pearson's correlation coefficient (r) between variables of interest and prostate-specific antigen, Homeostasis Model Assessment-Insulin Resistance, and body mass index among prostate cancer patients|
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|Figure 2: Positive Pearson's correlation between serum prostate-specific antigen and total cholesterol|
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|Figure 3: Positive Pearson's correlation between serum prostate-specific antigen and Homeostasis Model Assessment-Insulin Resistance|
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|Figure 4: Negative Pearson's correlation between serum prostate-specific antigen and high-density lipoprotein-cholesterol|
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|Figure 5: Positive Pearson's correlation between Homeostasis Model Assessment-Insulin Resistance and fasting glucose|
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[Table 3] shows the estimation of the unadjusted OR (95% CI) and adjusted * OR (95% CI) for prostate cancer risk. Unadjusted logistic regression model showed a significant association (OR [95% CI], P < 0.001) between BMI (4.7 [2.61–8.64]), glucose (8.2 [3.3–20.3]), total cholesterol (5.7 [3.07–10.5]), HDL-C (1.5 [1.24–1.84]), TGs (5.6 [3.04–10.4]), HOMA-IR (2.94 [2.23–3.86]), and prostate cancer risk. In univariate analysis, variables statistically significant with prostate cancer risk (P< 0.10) were included in the multivariate logistic regression model. Multivariate models were adjusted by all variables in the models. The binary logistic regression analysis showed a significant association (adjusted * OR with 95% CI, P < 0.001) between total cholesterol (5.27 [1.87–14.8]), HDL-C (1.73 [1.02–3.42]), TGs (1.24 [1.05–1.37]), HOMA-IR (2.68 [1.53–4.62]), and prostate cancer.
|Table 3: Unadjusted and adjusted odds ratios and 95% confidence limits for prostate cancer in relation to age, BMI, total cholesterol, HDL-C, TGS, fasting glucose, serum insulin, and HOMA-IR by applying binary logistic regression|
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| Discussion|| |
In this study, we examined the effect of dyslipidemia, hyperinsulinemia, and IR on the risk of prostate cancer. The logistic regression analysis models showed a significant association between BMI, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, low HDL-C, HOMA-IR, and increased risk for prostate cancer. Associations with BMI and high glucose lost significance upon multivariate adjustment models. Previously, we provided evidence supporting a relationship of dyslipidemia, IR, and PSA with prostate cancer. Here, we provided further evidence showing that dyslipidemia and IR may influence the risk of prostate cancer.
Total cholesterol, triglycerides, and high-density lipoprotein-cholesterol
In our study we found that disturbed lipid profile was significantly associated with prostate cancer patients as compared to control patients. It is known that cholesterol plays an important role in prostate cancer as a precursor of androgens, cell proliferation mediator, and inflammation. Cholesterol is also included within the lipid bimolecular layer of the cell membrane and this includes prostate cancer cells. Several experimental studies using in vitro models have shown that triglyceride-rich remnant-like particles induce carcinogenesis by upregulating cell signaling pathways, such as the MEK/ERK and AKT pathways, involved in controlling cell growth and proliferation, apoptosis, cell cycle arrest, and lipid biosynthesis.,, It has been suggested that HDL plays a protective role in the pathophysiology and cancer progression., Low HDL effect could be explained by reduced binding of paraoxonase-1 (PON-1), thus reducing PON-1 free radical scavenging capacity. In addition, HDL may convey some protection from cancer severity by inhibiting the formation of lipid rafts which have been associated with procarcinogenic cell signaling through the activity of Caveolin-1 (Cav-1). We also observed in our study that when HDL-C level decreased in men then there was a rise in serum PSA level.
There is a gathering body of research to explore the inter-relationship between lipid and cancer, particularly prostate cancer development and progression. Four prospective studies found positive associations between total cholesterol and higher grade or more advanced prostate cancer.,,, Han et al., however, did not find any association between total cholesterol, TGs, and PSA. In contrast to our findings, one study including 6774 Chinese men reported an inverse association between TGs and PSA levels. Similar to our study, some other studies reported that the patients with prostate cancer had a statistically significant elevated cholesterol-to-HDL ratio and higher triglyceride level compared with normal individuals. It was concluded that higher cholesterol levels associated with lower HDL levels could be a risk factor for prostate cancer., A positive correlation was also found between serum TGs and prostate cancer with an OR (95% CI) of 1.14 (1.003–1.315; P < 0.05) after correcting for age, BMI, diabetes, and comedication with statin. Platz et al. reported that men with low cholesterol <200 mg/dL had a lower risk of Gleason 8–10 prostate cancer (OR [95% CI], 0.41 [0.22–0.77]) than men with high cholesterol (≥200 mg/dL).
Fasting glucose, serum insulin, and insulin resistance
Hyperglycemia has been positively associated with cancers such as pancreatic, breast, and colorectal. However, its link with prostate carcinogenesis is conflicting. Several studies found evidence of higher risk of more aggressive or advanced prostate cancer among men with abnormal glucose levels, with the association being nonsignificant in two of the studies.,,,, Conversely, several other studies reported a protective effect of hyperglycemia or diabetes against higher grade or more advanced prostate cancer.,, For several decades, glucose has been documented as an important source of energy for rapid tumor cell proliferation. Evidence from clinical and genetic studies has also linked the hyperglycemic environment to carcinogenic processes such as apoptosis, oxidative stress, DNA damage, and chronic inflammation, which may drive the aggressiveness and progression of cancer.,,, For instance, one mouse study found that translation of the glycolytic enzyme hexokinase-2 was increased in prostate cancer cells due to loss of Pten and p53, which help to prevent cells from growing uncontrollably. GLUT12, an important protein in the glycolytic pathway, was also observed to be highly expressed by prostate cancer cells and may potentially help to facilitate the high energy needs of tumor cells. Serum glucose is directly controlled by insulin, thus higher glucose level induces insulin secretion from pancreatic beta cells. The high level of circulating insulin decreases the production of insulin-like growth factor (IGF-I)-binding proteins, increases the level of IGF-1, and increases the production of advanced glycation end products, which promote carcinogenesis. Lehrer et al. showed higher insulin levels to be present in patients with high-risk prostate cancer. In addition, diet-induced hyperinsulinemia was associated with increased tumor growth in a xenograft model.
IR may alter the risk of prostate cancer through several biologic pathways, including the obesity-sex hormone pathway. Abdominal obesity, especially visceral fat, is associated with increased hepatic glucose production and reduced glucose metabolism, higher levels of free fatty acids, and lower levels of sex hormone-binding globulin (thereby yielding higher levels of unbound testosterone). Reports of the IR in relation to prostate cancer risk have been conflicting. Hsing et al. and Albanes et al. reported that increased IR was associated with a higher risk of prostate cancer among Chinese men., In contrast, Stocks et al. reported that HOMA-IR was strongly inversely related to overall prostate cancer risk, especially among young men and among men with nonaggressive disease.,
| Conclusion|| |
Our study suggests that dyslipidemia, disturbed glucose metabolism, and IR are risk factors for prostate cancer in Indian males. Our study has particularly put forth significant differences in metabolic indices and lipid profile between prostate cancer patients and controls. Among biochemical parameters, glucose, total cholesterol, TGs, LDL-C, VLDL-C, serum insulin, HOMA-IR, and serum PSA are significantly elevated in patients with prostate cancer in comparison to controls. In our study, we show significant positive correlation between serum PSA and total cholesterol, TGs, LDL-C, serum insulin, and IR in prostate cancer patients. Serum HDL-C significantly decreased in prostate cancer patients and showed significant negative correlation with serum PSA. We also suggest significant association between hypercholesterolemia, hypertriglyceridemia, low HDL-C, HOMA-IR, and increased risk for prostate cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Cancer Research Fund International/American Institute for Cancer Research. World Cancer Research Fund International/American Institute for Cancer Research Continuous update Project Report: Diet, Nutrition, Physical Activity, and Prostate Cancer; 2014. Available from: http://www.wcrf.org/sites/default/files/Prostate-Cancer-2014-Report.pdf
. [Last accessed on 2018 Feb 21].
Kachhawa P, Kachhawa K, Singh S, Sarkar PD, Agrawal D, Kumar S, et al
. Relationship of dyslipidemia, insulin resistance, and prostatespecific antigen with prostate cancer. Oncobiol Targets 2016;3:7. [Full text]
Arthur R, Rodríguez-Vida A, Zadra G, Møller H, Van Hemelrijck M. Serum lipids as markers of prostate cancer occurrence and prognosis? J Clin Lipidol 2015;10:145-65.
Bhindi B, Locke J, Alibhai SM, Kulkarni GS, Margel DS, Hamilton RJ, et al
. Dissecting the association between metabolic syndrome and prostate cancer risk: Analysis of a large clinical cohort. Eur Urol 2015;67:64-70.
Martin RM, Vatten L, Gunnell D, Romundstad P, Nilsen TI. Components of the metabolic syndrome and risk of prostate cancer: The HUNT 2 cohort, Norway. Cancer Causes Control 2009;20:1181-92.
Sekine Y, Koike H, Nakano T, Nakajima K, Takahashi S, Suzuki K, et al
. Remnant lipoproteins induced proliferation of human prostate cancer cell, PC-3 but not LNCaP, via low density lipoprotein receptor. Cancer Epidemiol 2009;33:16-23.
Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, et al
. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab 2014;19:393-406.
Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, et al
. Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep 2014;8:1461-74.
Chandler JD, Williams ED, Slavin JL, Best JD, Rogers S. Expression and localization of GLUT1 and GLUT12 in prostate carcinoma. Cancer 2003;97:2035-42.
Flavin R, Zadra G, Loda M. Metabolic alterations and targeted therapies in prostate cancer. J Pathol 2011;223:283-94.
Harish K, Dharmalingam M, Himanshu M. Study protocol: Insulin and its role in cancer. BMC Endocr Disord 2007;7:10.
Morote J, Celma A, Planas J, Placer J, de Torres I, Olivan M, et al
. Role of serum cholesterol and statin use in the risk of prostate cancer detection and tumor aggressiveness. Int J Mol Sci 2014;15:13615-23.
Sekine Y, Koike H, Nakano T, Nakajima K, Suzuki K. Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells. Clin Chim Acta 2007;383:78-84.
Kachhawa K, Varma M, Kachhawa P, Agrawal D, Shaikh MK, Kumar S. Study of dyslipidemia and antioxidant status in chronic kidney disease patients at a hospital in South East Asia. J Health Res Rev 2016;3:28-30. [Full text]
Kotani K, Sekine Y, Ishikawa S, Ikpot IZ, Suzuki K, Remaley AT, et al
. High-density lipoprotein and prostate cancer: An overview. J Epidemiol 2013;23:313-9.
Eroglu M, Yilmaz N, Yalcinkaya S, Ay N, Aydin O, Sezer C, et al
. Enhanced HDL-cholesterol-associated anti-oxidant PON-1 activity in prostate cancer patients. Kaohsiung J Med Sci 2013;29:368-73.
Yang G, Timme TL, Frolov A, Wheeler TM, Thompson TC. Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression. Cancer 2005;103:1186-94.
Mondul AM, Clipp SL, Helzlsouer KJ, Platz EA. Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort. Cancer Causes Control 2010;21:61-8.
Platz EA, Till C, Goodman PJ, Parnes HL, Figg WD, Albanes D, et al
. Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 2009;18:2807-13.
Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS, et al
. Cholesterol and the risk of grade-specific prostate cancer incidence: Evidence from two large prospective cohort studies with up to 37 years' follow up. BMC Cancer 2012;12:25.
Han JH, Chang IH, Ahn SH, Kwon OJ, Bang SH, Choi NY, et al
. Association between serum prostate-specific antigen level, liver function tests and lipid profile in healthy men. BJU Int 2008;102:1097-101.
Liu M, Wang JY, Zhu L, Wan G. Body mass index and serum lipid profile influence serum prostate-specific antigen in Chinese men younger than 50 years of age. Asian J Androl 2011;13:640-3.
Magura L, Blanchard R, Hope B, Beal JR, Schwartz GG, Sahmoun AE, et al
. Hypercholesterolemia and prostate cancer: A hospital-based case-control study. Cancer Causes Control 2008;19:1259-66.
Salgado-Montilla J, Soto Salgado M, Surillo Trautmann B, Sánchez-Ortiz R, Irizarry-Ramírez M. Association of serum lipid levels and prostate cancer severity among Hispanic Puerto Rican men. Lipids Health Dis 2015;14:111.
Wuermli L, Joerger M, Henz S, Schmid HP, Riesen WF, Thomas G, et al
. Hypertriglyceridemia as a possible risk factor for prostate cancer. Prostate Cancer Prostatic Dis 2005;8:316-20.
Lambe M, Wigertz A, Garmo H, Walldius G, Jungner I, Hammar N, et al
. Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer. Cancer Causes Control 2011;22:1163-71.
Arthur R, Møller H, Garmo H, Holmberg L, Stattin P, Malmstrom H, et al
. Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories. Cancer Med 2016;5:1307-18.
Sharma N, Sood S, Kaushik GG, Ali Z. Risk of prostate cancer and its correlation with different biochemical parameters in nondiabetic men. Int J Res Med Sci 2013;1:476-81.
Kang J, Chen M, Zhang Y, Moran BJ, Dosoretz DE, Katin MJ, et al
. Type of diabetes mellitus and the odds of Gleason score 8-10 prostate cancer. Int J Radiat Oncol Biol Phys 2012;82:e463-7.
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.
Calton BA, Chang SC, Wright ME, Kipnis V, Lawson K, Thompson FE, et al
. History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP diet and health study. Cancer Causes Control 2007;18:493-503.
Fall K, Garmo H, Gudbjörnsdottir S, Stattin P, Zethelius B. Diabetes mellitus and prostate cancer risk; a nationwide case-control study within PCBaSe Sweden. Cancer Epidemiol Biomarkers Prev 2013;22:1102-9.
Warburg O. On the origin of cancer cells. Science 1956;123:309-14.
Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 2007;132:2208-25.
Kachhawa K, Agrawal D, Rath B, Kumar S. Association of lipid abnormalities and oxidative stress with diabetic nephropathy. J Integr Nephrol Androl 2017;4:3-9. [Full text]
Abe R, Yamagishi S. AGE-RAGE system and carcinogenesis. Curr Pharm Des 2008;14:940-5.
Lehrer S, Diamond EJ, Stagger S, Stone NN, Stock RG. Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer. Br J Cancer 2002;87:726-8.
Venkateswaran V, Haddad AQ, Fleshner NE, Fan R, Sugar LM, Nam R, et al
. Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. J Natl Cancer Inst 2007;99:1793-800.
Hsing AW, Deng J, Sesterhenn IA, Mostofi FK, Stanczyk FZ, Benichou J, et al
. Body size and prostate cancer: A population-based case-control study in china. Cancer Epidemiol Biomarkers Prev 2000;9:1335-41.
Garaulet M, Pérex-Llamas F, Fuente T, Zamora S, Tebar FJ. Anthropometric, computed tomography and fat cell data in an obese population: Relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones. Eur J Endocrinol 2000;143:657-66.
Hsing AW, Gao YT, Chua S Jr., Deng J, Stanczyk FZ. Insulin resistance and prostate cancer risk. J Natl Cancer Inst 2003;95:67-71.
Albanes D, Weinstein SJ, Wright ME, Männistö S, Limburg PJ, Snyder K, et al
. Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 2009;101:1272-9.
Stocks T, Lukanova A, Rinaldi S, Biessy C, Dossus L, Lindahl B, et al
. Insulin resistance is inversely related to prostate cancer: A prospective study in Northern Sweden. Int J Cancer 2007;120:2678-86.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]