Null genotypes at the GSTM1 and GSTT1 genes and the risk of benign prostatic hyperplasia: a case-control study and a meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age related non-malignant disease diagnosed as lower urinary tract symptoms and prostatic enlargement. Null genotypes in drug detoxification glutathione-S-transferase genes/enzymes, such as GSTT1 and GSTM1 have been reported to increase risk of several cancers including prostate. Meta-analysis on PC also suggested significant impact of GSTM1 null genotype but not that of GSTT1; however, BPH data have not been subjected to meta-analysis. METHODS: We investigated GSTT1 and GSTM1 genotypes in 429 subjects which included 244 BPH, 51 prostate cancer (PC) patients, and 134 control subjects to find if null genotype in any of the two genes increased the risk of BPH/PC. We also performed a quantitative meta-analysis on 888 BPH cases and 793 controls for GSTM1 and on 890 BPH cases and 793 controls for GSTT1 to assess overall consensus about the impact of null genotypes on BPH risk. RESULTS: We did not find any significant difference in the distribution of genotypes of either of the two genes between BPH/PC cases and controls; however, double deletion (GSTM1 null + GSTT1 null) increased BPH risk, significantly. Upon meta-analysis, null genotype of GSTM1 but not that of GSTT1 appeared to strongly affect BPH risk. CONCLUSIONS: In our population, null genotypes of either GSTM1 or GSTT1 do not appear to affect BPH risk; however, the double deletion was significantly associated with BPH. Meta-analysis suggested significant influence of GSTM1 null genotype but not that of GSTT1 on BPH risk.

Significance of obesity markers and adipocytokines in high grade and high stage prostate cancer in North Indian men - a cross-sectional study.

BACKGROUND: Prostate cancer (CaP) in India is the 10th most common malignancy affecting men. CaP incidence in India is low, but rising like other countries. The reasons for this racial disparity are uncertain. The foremost reasons that may underlie regional/ethnic differences are genetic polymorphisms, altered hormonal status, socioeconomic status, and obesity. This study aimed at investigating the role of adipocytokines in stimulating the promotion and progression of CaP. METHODS: A cross-sectional study on histopathologically proven prostate cancer (N=95) and benign prostatic hyperplasia (N=95) patients was undertaken. CaP patients were classified into high-grade (N=62) and low-grade (N=33), and high stage (N=31) and low stage (N=64) groups. The level of body mass index (BMI), waste to hip ratio (WHR), interleukin-6 (IL-6), leptin, and adiponectin were compared between BPH and CaP groups and between grades and stages of prostate cancer. RESULTS: The level of BMI was significantly (p<0.001) higher in CaP patients (26.58±4.76) in comparison to BPH (22.15±2.90). Similarly, WHR was significantly (p<0.0001) higher in the CaP patients (1.08±0.37) in comparison to BPH (0.86±0.15). Leptin (BPH: 25.60, CaP: 56.00) and II-6 levels (BPH: 9.90, CaP: 32.30) were significantly higher, but adiponectin was significantly lower in CaP patients as compared to BPH. High grade CaP patients had significantly higher BMI and WHR in comparison to low grade, and WHR was also higher in high stage CaP. Leptin and IL-6 level were higher in high stage and high grade, but adiponectin was low in high stage and high grade groups in comparison to low stage and low grade groups. CONCLUSIONS: Higher BMI and WHR correlate with prostate cancer independently, suggesting obesity to be a promoter of poor prostate health. Leptin and IL-6 appear to have stimulating effect on prostate cancer cells inducing the promotion and progression of CaP, but adiponectin appears to be protective against prostate cancer.

Significant association of metabolic indices, lipid profile, and androgen levels with prostate cancer.

OBJECTIVES: To compare the metabolic indices, lipid profile, androgens, and prostate specific antigen between prostate cancer and BPH and between grades of prostate cancer in a cross-sectional study. MATERIALS AND METHODS: The study enrolled 95 cases of prostate cancer and 95 cases of benign prostatic hyperplasia (BPH). Prostate gland volume was measured using transrectal ultrasound. We compared insulin, testosterone, dihydrotestosterone, prostate specific antigen levels and lipid profile between prostate cancer of different grades and BPH. Further, prostate cancer patients were classified into low grade and high grade. Unpaired t-test for normally distributed variables and Man-Whitney U test for non-normal variables were used to assess differences. RESULTS: We found that prostate cancer patients had significantly higher levels of insulin, testosterone, PSA, cholesterol, triglycerides, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in comparison to their BPH counterparts. Higher levels of these parameters also correlated with a higher grade of the disease. CONCLUSIONS: We conclude that higher levels of insulin, testosterone, PSA, and cholesterol correlate with a higher risk of prostate cancer, and also with a higher grade of the disease.

Effect of rifaximin, probiotics, and l-ornithine l-aspartate on minimal hepatic encephalopathy: a randomized controlled trial.

BACKGROUND/AIMS: Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group. PATIENTS AND METHODS: This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30). RESULTS: Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group. CONCLUSIONS: Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE.

Diet, obesity, and prostate health: are we missing the link?

Prostate problems, such as benign prostatic hyperplasia, prostatic intra-epithelial neoplasia, prostatitis, and prostate cancer have been recognized as problems largely related to androgens and genetic factors. They affect a large fraction of the elderly population, contributing significantly to morbidity and mortality. Estrogen has also now been recognized as one of the important regulators of prostate growth. Diet, general health, and obesity were disregarded as the causative or complicating factors until very recently. Increasing episodes of prostate problems, complications in overweight/obese individuals, or both have attracted attention toward these contemporary risk factors. Prostate problems are reportedly less frequent or less severe in areas in which a plant-based diet is predominant. Consumption of certain fatty acids, particularly of animal origin, has been correlated with increased prostate problems. As adipose tissue is increasingly being regarded as hormonally active tissue, high body fat and obesity need in-depth exploration to understand the associated risk of prostate problems. Adipose tissue is now known to affect circulating levels of several bioactive messengers and therefore could affect the risk of developing prostate problems in addition to several other well-recognized health problems. Nevertheless, increased plasma volume, excess tissue growth, and fat deposition could affect resection and number of biopsies required, thus adding further complications because of a delayed diagnosis. In short, evidence is gathering to support the influence of diet and obesity on prostate health. In this review article, we have tried to make this connection more apparent using supporting published data.

Is central obesity, hyperinsulinemia and dyslipidemia associated with high-grade prostate cancer? A descriptive cross-sectional study.

AIMS: The association of central obesity, hyperinsulinemia, and dyslipidemia with higher grade advanced prostate cancer as determined by Gleason grading is not well understood. We evaluated the effect of central obesity waist hip ratio (WHR ≥ 0.9) and biochemical parameters associated with central obesity on Gleason grading in North Indian patients of prostate cancer presenting at advanced stages. MATERIALS AND METHODS: A cross-sectional study was conducted among 50 nondiabetic patients having clinical stages III and IV prostate cancer. Gleason grading on core biopsy samples by histopathology was done and patients were divided in two groups-group1, Gleason score ≥8; group 2, Gleason score <8. WHR along with serum levels of prostate-specific antigen (PSA), testosterone, insulin, and lipid profile was done in each patient. RESULTS: The two groups are similar in Age (67.54 years); range (50-80 years). Group 1 men had statistically higher mean WHR (0.96 vs 0.90; P ≤ 0.001), higher mean triglyceride level (201.34 vs 150.52 mg/dL; P=0.0006), higher mean very low-density lipoprotein (VLDL) (40.27 vs 30.10 mg/dL; P =0.0006), higher mean insulin (19.49 vs 15.04 µIU/mL; P = 0.0024), and lower mean high-density lipoprotein (HDL) levels (32.39 vs 36.82 mg/dL; P = 0.034) than men in group 2. Serum levels of cholesterol, LDL, and testosterone did not show statistically significant differences between the two groups. CONCLUSIONS: This pilot study involving small number of patients indicates that central obesity, dyslipidemia, and hyperinsulinemia could be associated with high-grade prostate cancer.