Displaying publications 61 - 80 of 149 in total

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  1. Lokamani I, Looi ML, Md Ali SA, Mohd Dali AZ, Ahmad Annuar MA, Jamal R
    Pathol Oncol Res, 2014 Jan;20(1):119-29.
    PMID: 23925487 DOI: 10.1007/s12253-013-9670-9
    This study aimed to identify candidate proteins which may serve as potential biological markers for cervical cancer using 2D-DIGE. Serum samples of controls, patients with cervical intraepithelial neoplasia grade 3 (CIN 3), squamous cell carcinoma of early (SCC I and II) and late (SCC III and IV) stage were subjected to 2D-DIGE. Differentially expressed spots were identified by tandem mass spectrometry. Validation of candidate proteins in serum and tissue samples were then performed by ELISA and immunohistochemistry (IHC) analysis respectively. A total of 20 differentially expressed proteins were identified. These proteins were found to play key roles in the apoptosis pathway, complement system, various types of transportation such as hormones, fatty acids, lipid, vitamin E and drug transportation, coagulation cascade, regulation of iron and immunologic response. Based on their functional relevancy to the progression of various cancers, 4 proteins namely the complement factor H, CD5-like antigen, gelsolin and ceruloplasmin were chosen for further validation using ELISA. Biological network analysis showed that ceruloplasmin and gelsolin are closely interacted with the oncogene NF-κb. These two proteins were further validated using the IHC. Gelsolin and ceruloplasmin may serve as potential predictive biomarkers for the progression of high grade lesions.
    Matched MeSH terms: Uterine Cervical Neoplasms/blood*
  2. Loch A, Singh RV, Abidin IZ, Han CK, Ahmad WA
    J Thorac Oncol, 2011 Jul;6(7):1292.
    PMID: 21847043 DOI: 10.1097/JTO.0b013e31821f9771
    Matched MeSH terms: Breast Neoplasms/blood
  3. Hong GE, Kong CH, Singam P, Cheok LB, Zainuddin ZM, Azrif M
    Asian Pac J Cancer Prev, 2010;11(5):1351-3.
    PMID: 21198291
    INTRODUCTION: Analysis of epidemiological as well as survival differences among the multiethnic population of Malaysia with prostate cancer is important.

    METHODS: Patients confirmed by transrectal-ultrasonographic-guided-biopsy performed from 2002 to 2008 were enrolled and analysed according to ethnicity, age, PSA level, Gleason score, stage of disease and survival.

    RESULTS: Among 83 patients, there were 38 Malay, 40 Chinese, 3 Indians and 2 others. Median age at diagnosis was 69.9 (range: 59-93), 43 patients (51.8%) being diagnosed before the age of 70. The median PSA level upon diagnosis was 574 ng/ml (range: 1-8632) and the median Gleason score was 7 (range: 2-10). Over half were already in Stage 4 when diagnosed. The most common site of metastasis was the bone. As a result the commonest prescribed treatment was hormonal manipulation. Five patients underwent radical prostatectomy and a further thirteen patients had radical radiotherapy (stage I: 1 patient, stage II: 7 patients and stage III: 5 patients). Ten patients defaulted follow-up. The median disease-specific survival was 21.9 months (range: 1-53).

    CONCLUSIONS: Prostatic carcinoma is a disease of the elderly and it is frequently diagnosed late in Malaysia. Greater efforts should be made to educate Malaysians regarding prostate cancer.

    Matched MeSH terms: Prostatic Neoplasms/blood
  4. Shahar S, Salleh RM, Ghazali AR, Koon PB, Mohamud WN
    Asian Pac J Cancer Prev, 2010;11(1):61-6.
    PMID: 20593932
    BACKGROUND: Lack of physical activities throughout life is related to obesity and is a risk factor of breast cancer, however, the associations of these factors with adiponectin in the occurrence of breast cancer have not been well investigated.

    OBJECTIVE: This study investigated the relationship between adiposity, lifetime physical activities and serum adiponectin as breast cancer risk factors among Malaysian women in Klang Valley, Malaysia.

    DESIGN: A case-control study was carried out among 70 newly diagnosed breast cancer patients and 138 controls aged 29 to 65 years old in Klang Valley.

    SUBJECTS: The inclusion criteria for both groups were not having menstruation for premenopausal women, no evidence of pregnancy, not lactating and no chronic diseases such as hypertension and diabetes at the time of data collection. In addition, the cases must be pathologically newly diagnosed with breast cancer (stage I to III) and not on any therapy for cancer, with the exception of surgery. The controls were matched with cases for age +/- 5 years and menopausal status.

    MEASUREMENTS: Subjects were interviewed to obtain information on socio-demography, health and reproductive history using a pretested questionnaire. Subjects were also asked on their engagement of physical activity since secondary school. Anthropometric parameters included height, weight, waist and hips were also measured. A total of 6 ml of fasting venous blood was drawn for analysis of serum adiponectin in duplicate using Linko Adiponectin ELISA Kit. Fasting blood glucose (FBG) and blood pressure were also measured.

    RESULTS: Mean body mass index (BMI) among cases and controls were not significantly different (p> 0.05) at 26.1 -/+ 4.8 kg/m2 and 25.3 -/+ 4.5 kg/m2, respectively. FBG among cases (6.3 -/+ 1.8 mmol/L) was higher than controls (5.6 -/+ 1.1 mmol/L) (p<0.05). Waist hip ratio (WHR) of cases (0.85 -/+ 0.07) was also higher than controls (0.80 -/+ 0.06) (p<0.05). Abdominal obesity (WHR > 0.85) increased risk of breast cancer by three folds [Adjusted OR 3.3 (95%CI 1.8-6.2)] (p<0.05). Adiponectin level was inversely related to waist circumference (r=-0.510, p=0.000), BMI (r=-0.448, p=0.000) and FBG (r=-0.290, p=0.026). Adiponectin level in cases (11.9 -/+ 4.8 microg/ml) were lower than controls (15.2 -/+ 7.3 microg/ml) (p<0.05). A greater reduction of breast cancer risk was observed with the increasing level of serum adiponectin level according to percentiles (p<0.05). Subjects with mean serum adiponectin level at the highest quintile (> 75th)( >or= 16.7 microg/ml) had 80% reduced risk of breast cancer [Adjusted OR 0.2 (0.0-0.6)](p<0.05). A higher percentage of cases (47%) had not engaged in any physical activity throughout life as compared to controls (19%)[Adjusted OR 3.7 (1.7-7.7)](p<0.001).

    CONCLUSIONS: Abdominal obesity and physical inactivity throughout life were associated with low serum adiponectin and breast cancer risk among subjects. Thus, it is essential for Malaysian women to be physically active and achieve a healthy waistline in order to increase serum adiponectin level and reduce breast cancer risk.

    Matched MeSH terms: Breast Neoplasms/blood*
  5. Pang WW, Abdul-Rahman PS, Wan-Ibrahim WI, Hashim OH
    Int. J. Biol. Markers, 2010 Jan-Mar;25(1):1-11.
    PMID: 20155712
    The association between the acute-phase reactant proteins (APRPs) and cancer has long been established. There have been numerous reports correlating altered levels of various APRPs with different types of cancers. However, researchers are often quick to dismiss the use of these APRPs as potential biomarkers for the diagnosis and monitoring of cancer because alterations in APRP concentrations are observed in a wide range of diseases. Recent progress in proteomics studies which profiled the serum proteins of cancer patients and those of normal individuals indicated that the altered APRP expressions were different for distinct types, subtypes, and even stages of cancer. Interestingly, these data are in agreement with those observed earlier using immunochemical and biochemical assays. In view of this compelling association of different patterns of APRPs with various types of cancers and in an apparent shift of paradigm, we present in this review some indications that APRP fingerprinting may be used as complementary cancer biomarkers.
    Matched MeSH terms: Neoplasms/blood*
  6. Wan-Ibrahim WI, Ashrafzadeh A, Singh VA, Hashim OH, Abdul-Rahman PS
    Electrophoresis, 2016 09;37(17-18):2328-37.
    PMID: 27062367 DOI: 10.1002/elps.201500522
    Sarcoma is a malignant tumor that originates from the bone or soft tissue. In this study, abundances of serum amyloid A (SAA) in patients with pleomorphic sarcoma (PS), chondrosarcoma (CS), and osteosarcoma (OS) were analyzed and compared with those from their respective age-matched healthy control subjects. Results obtained from our analysis by 2DE showed that the levels of SAA were markedly elevated in patients with PS and OS, which are highly metastatic, while in patients with CS, which is a less aggressive sarcoma, the increase appeared less pronounced. A similar trend of altered abundances was also observed when the levels of SAA in the subjects were estimated using Western blot, ELISA, and multiple-reaction monitoring analyses. Absolute quantification using multiple-reaction monitoring further demonstrated that the increased abundance of SAA in patients with PS, OS, and CS was mainly attributed to isoform SAA1. In view of the different degrees of tumor malignancy in PS, OS, and CS, our data suggest their apparent correlation with the levels of SAA in the patients.
    Matched MeSH terms: Bone Neoplasms/blood
  7. Kamariah K, Satgunasingam N, Nasri NM, Ng KY
    Med J Malaysia, 1993 Mar;48(1):40-5.
    PMID: 7688063
    Eighty-nine patients who had hydatidiform moles evacuated at the General Hospital, Kuala Lumpur, were followed with serum beta hCG determinations from October 1988 to June 1991. A regression curve for serum beta hCG, as measured by RIA, was derived from the results of 47 of the patients who demonstrated spontaneous regression of serum beta hCG titres. All 47 patients had normal serum titres at 135 days after evacuation. The mean time taken to reach normal level was 82.6 days, while the range was 39 to 135 days (5 to 19 weeks).
    Matched MeSH terms: Uterine Neoplasms/blood*
  8. Lopez JB, Sahabudin RM, Chin LP
    Int. J. Biol. Markers, 2004 Apr-Jun;19(2):164-7.
    PMID: 15255551
    Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.
    Matched MeSH terms: Prostatic Neoplasms/blood*
  9. Antwi SO, Bamlet WR, Pedersen KS, Chaffee KG, Risch HA, Shivappa N, et al.
    Carcinogenesis, 2018 07 30;39(8):1056-1067.
    PMID: 29800239 DOI: 10.1093/carcin/bgy072
    Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n = 2414; controls, n = 4528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n = 1268; controls, n = 4215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (E-DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 [ORQ5 versus Q1=2.20, 95% confidence interval (CI) = 1.85-2.61, Ptrend < 0.0001; ORcontinuous = 1.20, 95% CI = 1.17-1.24], and PanScan (ORQ5 versus Q1 = 1.23, 95% CI = 0.92-1.66, Ptrend = 0.008; ORcontinuous = 1.09, 95% CI = 1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction = 0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.
    Matched MeSH terms: Pancreatic Neoplasms/blood*
  10. Chong ZX, Yeap SK, Ho WY
    Arch Biochem Biophys, 2020 11 30;695:108583.
    PMID: 32956633 DOI: 10.1016/j.abb.2020.108583
    miRNAs are short non-coding RNA molecules that regulate the expression of mRNA post-transcriptionally. MiRNAs that are secreted into the circulation, also termed circulating miRNAs, have been studied extensively for their roles in diagnosis, treatment and prognosis of human breast cancer. Breast cancer is the most prevalent female cancer and is associated with key cancer hallmarks including sustained proliferation, evasion of apoptosis, increased invasion, enhanced metastases, initation of inflammation, induction of angiogenesis, metabolic derangement and immune dysregulation. This review aimed to explore the relationships between circulating miRNAs and different breast cancer hallmarks. Besides, the advantages, challenges and clinical application of using circulating miRNAs in human breast cancer management were also discussed.
    Matched MeSH terms: Breast Neoplasms/blood*
  11. Yap NY, Yap FN, Perumal K, Rajandram R
    Biomarkers, 2019 Sep;24(6):607-614.
    PMID: 31215811 DOI: 10.1080/1354750X.2019.1634763
    Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels. Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC. Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan. Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels. Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.
    Matched MeSH terms: Kidney Neoplasms/blood
  12. Yang YF, Mattamel PB, Joseph T, Huang J, Chen Q, Akinwunmi BO, et al.
    Nutrients, 2021 Apr 21;13(5).
    PMID: 33918992 DOI: 10.3390/nu13051388
    BACKGROUND: The role of low-carbohydrate ketogenic diet (LCKD) as an adjuvant therapy in antitumor treatment is not well established. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the efficacy of LCKD as an adjuvant therapy in antitumor treatment compared to non-ketogenic diet in terms of lipid profile, body weight, fasting glucose level, insulin, and adverse effects; Methods: In this study, databases such as PubMed, Web of Science, Scopus, CINAHL, and Cochrane trials were searched. Only RCTs that involved cancer participants that were assigned to dietary interventions including a LCKD group and a control group (any non-ketogenic dietary intervention) were selected. Three reviewers independently extracted the data, and the meta-analysis was performed using a fixed effects model or random effects model depending on the I2 value or p-value; Results: A total of six articles met the inclusion/exclusion criteria. In the overall analysis, the post-intervention results = standard mean difference, SMD (95% CI) showed total cholesterol (TC) level = 0.25 (-0.17, 0.67), HDL-cholesterol = -0.07 (-0.50, 0.35), LDL-cholesterol = 0.21 (-0.21, 0.63), triglyceride (TG) = 0.09 (-0.33, 0.51), body weight (BW) = -0.34 (-1.33, 0.65), fasting blood glucose (FBG) = -0.40 (-1.23, 0.42) and insulin = 0.11 (-1.33, 1.55). There were three outcomes showing significant results in those in LCKD group: the tumor marker PSA, p = 0.03, the achievement of ketosis p = 0.010, and the level of satisfaction, p = 0.005; Conclusions: There was inadequate evidence to support the beneficial effects of LCKDs on antitumor therapy. More trials comparing LCKD and non-KD with a larger sample size are necessary to give a more conclusive result.
    Matched MeSH terms: Neoplasms/blood
  13. Liau CS, Mogan P, Thomas W
    J Steroid Biochem Mol Biol, 2021 04;208:105786.
    PMID: 33189851 DOI: 10.1016/j.jsbmb.2020.105786
    Lung cancer is increasing in incidence particularly among women, associated with a global change in smoking habits. Steroid hormones, particularly oestrogen exert an influence on tumour progression in tissues where their target receptor is expressed. Oestrogen receptor, particularly ERβ is highly expressed in the lung and becomes more highly expressed in lung carcinogenesis. Genes involved in the process of lung carcinoma progression and signalling cascades linked to invasion and angiogenesis are modulated by oestrogen receptors. This review intends to collate recently published evidence identifying a role for oestrogen in the initiation and progression of lung carcinoma and how these two processes are differentially affected by circulating oestrogens both in women and in men. Circulating oestrogens may be a significant risk factor in women's susceptibility to lung carcinoma and also provide an additional approach for more targeted therapy.
    Matched MeSH terms: Lung Neoplasms/blood*
  14. Mohamed Yusoff AA, Mohd Khair SZN, Wan Abdullah WS, Abd Radzak SM, Abdullah JM
    J Cancer Res Ther, 2020 12 22;16(6):1517-1521.
    PMID: 33342822 DOI: 10.4103/jcrt.JCRT_1132_16
    Background and Objective: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients.

    Materials and Methods: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds.

    Results: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions.

    Conclusion: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.

    Matched MeSH terms: Meningeal Neoplasms/blood
  15. Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.
    Ther Drug Monit, 2013 Oct;35(5):624-30.
    PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2
    Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
    Matched MeSH terms: Colorectal Neoplasms/blood
  16. Hawkins BR, Simons MJ, Goh EH, Chia KB, Shanmugaratnam K
    Int J Cancer, 1974 Jan 15;13(1):116-21.
    PMID: 4206461 DOI: 10.1002/ijc.2910130113
    Matched MeSH terms: Nasopharyngeal Neoplasms/blood
  17. Abubakar MB, Gan SH
    Niger J Physiol Sci, 2017 Dec 30;32(2):219-225.
    PMID: 29485645
    Although anastrozole (Anas) plays a key role in the management of endocrine sensitive post-menopausal (PM) breast cancer (BC), there is much variability in its efficacy and tolerability. Anas-associated musculoskeletal symptoms (MS) and other adverse reactions, such as hot flashes (HF) and vaginal dryness/dyspareunia (VDD), are common and can affect the quality of life of BC patients, even sometimes leading to treatment withdrawal. The aim of this study was to determine the clinical and demographic factors associated with these adverse events. This is a cross-sectional study in estrogen receptor (ER) positive PM women (n = 92) with stages I to III BC receiving Anas. Multivariate analyses were performed to investigate the factors associated with Anas-induced adverse effects such as MS, HF and VDD. A serum estradiol concentration was undetectable (< 36.7 pmol/L) in 68.1% of patients but was detectable within a normal range (>36.7-88.1 pmol/L) in the other 31.9% of patients, and this group was found to have a lower odds of having at least one adverse effect (AE) compared to those with undetectable levels [adjusted odds ratio (AOR) 0.12, 95% confidence interval (CI) 0.02 to 0.64, p = 0.013]. Women with grades II and III tumors and a family history of BC had a higher odds of AE (grade II: AOR 12.22, CI 1.48 to 100.80, p = 0.020; grade III: AOR 12.95, CI 1.25 to 134.33, p = 0.032) and VDD (AOR 5.99, CI 1.30 to 27.52, p = 0.021), respectively. Patients who received Anas treatment for more than one year had a higher odds of VDD (one to three years: AOR 34.57, CI 3.86, 309.50, p = 0.002; more than 3 years: AOR 27.90, CI 2.21 to 351.84, p = 0.010). Advanced age also lowered the odds of HF (AOR 0.90, CI 0.83 to 1.00, p = 0.049). In conclusion, patients' hormonal environments and durations of Anas treatment may play a role in developing Anas-induced adverse effects.
    Matched MeSH terms: Breast Neoplasms/blood*
  18. Ho CC, Rohaizak M, Zulkifli SZ, Siti-Aishah MA, Nor-Aini U, Sharifah-Noor-Akmal SH
    Singapore Med J, 2009 May;50(5):513-8.
    PMID: 19495523
    This study was conducted to determine the association between serum sex hormone levels and breast cancer.
    Matched MeSH terms: Breast Neoplasms/blood*
  19. Yahaya N, Din SW, Ghazali MZ, Mustafa S
    Singapore Med J, 2011 Sep;52(9):e173-6.
    PMID: 21947158
    Primary thyroid lymphoma (PTL) is a rare form of thyroid cancer that is known to be associated with Hashimoto thyroiditis. This association is supported by the presence of elevated titres of both antithyroglobulin and antimicrosomal antibodies in up to 95 percent of patients with PTL. Most patients with PTL present with a rapidly enlarging neck mass and compressive symptoms. The majority of thyroid cancer patients have normal levels of thyroid hormones; they are rarely hyperthyroid, with no obvious clinical features of thyrotoxicosis. We describe a patient who presented with minimal clinical features of thyrotoxicosis despite having markedly elevated serum free thyroxine and suppressed serum thyroid-stimulating hormone levels.
    Matched MeSH terms: Thyroid Neoplasms/blood*
  20. Watts EL, Appleby PN, Perez-Cornago A, Bueno-de-Mesquita HB, Chan JM, Chen C, et al.
    Eur Urol, 2018 Nov;74(5):585-594.
    PMID: 30077399 DOI: 10.1016/j.eururo.2018.07.024
    BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.

    OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.

    DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.

    RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.

    CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.

    PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

    Matched MeSH terms: Prostatic Neoplasms/blood*
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