Anticancer potential of Phoenix dactylifera L. seed extract in human cancer cells and pro-apoptotic effects mediated through caspase-3 dependent pathway in human breast cancer MDA-MB-231 cells: an in vitro and in silico investigation.

BACKGROUND: Phoenix dactylifera L. has a diverse set of pharmacological properties due to its distinct phytochemical profile. The purpose of this study was to investigate the anticancer potential of Phoenix dactylifera seed extract (PDSE) in human breast cancer MDA-MB-231 and MCF-7 cells, as well as liver cancer HepG2 cells, and to investigate the anticancer efficacy in triple-negative MDA-MB-231 cells, followed by in silico validation of the molecular interaction between active components of PDSE and caspase-3, an apoptosis executioner protein . METHODS: In this study, human cancer cell lines were cultured and subsequently treated with 10 to 100 µg/mL of PDSE. MTT test was performed to determine the cell viability, MMP was measured using fluorescent probe JC-1, nuclear condensation was determined by Hoechst 33258 dye, Annexin V-FITC & PI staining and cell cycle analysis were evaluated through flow cytometer, and apoptotic markers were detected using western blotting. The bioactive agents in PDSE were identified using high-performance liquid chromatography (HPLC) analysis. The binding affinity was validated using molecular docking tools AutoDock Vina and iGEMDOCK v2.1. RESULTS: Cell viability data indicated that PDSE inhibited cell proliferation in both breast cancer cells and liver cancer cells. MDA-MB-231 cells showed maximum growth inhibition with an IC50 value of 85.86 µg/mL for PDSE. However, PDSE did not show any significant toxicity against the normal Vero cell line. PDSE induced MMP loss and formation of apoptotic bodies, enhanced late apoptosis at high doses and arrested cells in the S phase of cell cycle. PDSE activated the enzymatic activity of cleaved caspase-3 and caused the cleavage of poly-ADB ribose polymerase (PARP) protein. PDSE upregulated pro-apoptotic Bax protein markedly but  no significant effect on tumor suppressor protein p53, while it downregulated the anti-apoptotic Bcl-2 protein expression. HPLC analysis showed the presence of rutin and quercetin bioactive flavonols in ethanolic extract of PDS. Interestingly, both active components revealed a strong binding interaction with amino acid residues of caspase-3 (PDB ID: 2XYP; Hetero 4-mer - A2B2) protein. CONCLUSION: PDS could serve as a potential medicinal source for apoptotic cell death in human breast cancer cells and, thus, could be used as a promising and crucial candidate in anticancer drug development. This study warrants further in vivo research, followed by clinical investigation.

Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins.

Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC-MS) and investigated anticancer effects against MDA-MB-231 cells. LC-MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

Assessment of micronuclei counts as tumour marker in cervical carcinogenesis: A follow-up study.

OBJECTIVE: Micronuclei counts were performed in cervical smears with low-grade squamous intraepithelial lesions of the cervix (LSIL) to assess its potentiality as tumour marker in cervical carcinogenesis. METHODS: The cases studied were from the ongoing rural cervical cancer screening in west Lucknow, India. Micronuclei counts were performed in the cervical smears of 100 LSIL cases, and the number of cells with micronuclei was defined as micronucleated cells (MNC) and the number of micronuclei per 1000 cells as MNC score. Human papillomavirus (HPV) DNA testing was also done in 100 LSIL cases by GeneNav qPCR test. RESULTS: A high MNC score was found in 20 of the 100 LSIL cases while the counts were low in the remaining 80. Persistence of LSIL was seen in 19 of the 20 LSIL cases with high MNC score while only six cases of the 80 cases with low MNC score showed persistence. The persistence of LSIL was very high in cases with high MNC score. The multiple high-risk HPV types such as 18, 31, 33 and 35 were seen in 12 of the 100 LSIL cases and a high positivity rate was seen in women with high MNC score. The persistence of LSIL was also higher with HPV positivity. CONCLUSION: The study revealed correlation between high MNC score, persistence of LSIL and HPV positivity. Hence, MNC score can prove to be very useful in discriminating high-risk LSIL cases that are less likely to regress and possibly may progress to high-grade squamous intraepithelial lesions or carcinoma.

Clinicopathological correlation of cancer stem cell markers Oct-4 and CD133 expression as prognostic factor in malignant lesions of gallbladder: An immunohistochemical study.

BACKGROUND: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. AIM: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. SETTINGS AND DESIGN: This is a prospective case control study, conducted in medical college background. MATERIALS AND METHODS: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. STATISTICAL ANALYSIS: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ≥2 were considered as positive. RESULTS: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. CONCLUSION: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade.

Low Expression of MicroRNA335-5p Is Associated with Malignant Behavior of Gallbladder Cancer: A Clinicopathological Study.

Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cellular processes during cancer progression, identified to be involved in tumorgenesis of several cancers including cancers of digestive system. However its role in gallbladder inflammatory disease (GID) and gallbladder cancer (GBC) has not been well documented. The present study was aimed to investigate the clinical significance of hsa-miRNA-335-5p (miR-335) in GBC and GID. Subjects and Methods: This prospective case control study, conducted from July 1, 2014 to December 1, 2017 in Era's Lucknow Medical College & Hospital, India, evaluated miR-335 expression by real-time polymerase chain reaction. Hundred tissue samples GID (control; n=50) and GBC (case; n=50) were studied. Relative quantification of target miR-335 expression was examined using the comparative cycle threshold method. Their expression was correlated with different clinicopathological parameters. Fishers' exact test, Student's t-test, and Chi-square test were used as appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rate. Two sided P<0.05 was considered as significant. Results: miR-335 expression was found to be significantly low in GBC lesions when compared with GID lesions (P<0.001). The low expression level of miR-335 was correlated with histological grade (P=0.007), clinical stage (P<0.001), lymph node metastasis (P<0.001) and liver metastasis (P=0.016). Reduced expression of miRNA-335 was associated with a shorter median overall survival (7 months vs. 25 months) in GBC patients (P<0.001). Conclusions: Down regulation of miR-335 is associated with the severity of the disease and thus indicate that miR-335 expression may serve as prognostic marker for GBC.

Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells.

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide ß-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.

Correlation of CD133 and Oct-4 expression with clinicopathological and demographic parameters in oral squamous cell carcinoma patients.

OBJECTIVE: Squamous cell carcinoma of oral cavity is one of the most common cancers of Indian subcontinent with the 5-year survival rate of 50% despite the recent advances in the treatment. The aim of the present study was to study cancer stem cell markers CD133 and Oct-4 in oral squamous cell carcinoma (OSCC) patients and their correlation with clinicopathological variables. MATERIALS AND METHODS: This was a prospective study which included 50 cases of histopathologically proven squamous cell carcinoma of oral cavity. Expression of CD133 and Oct-4 was evaluated by immunohistochemistry (IHC) and their expression was correlated with various clinicopathological and demographic parameters. RESULTS: CD133 expression was seen in 20.6% cases of clinical Stage I-II and in 79.4% of clinical stage of III-IV OSCC patients, the difference being statistically significant with the P = 0.048. There was no statistically significant association between CD133 expression and any other clinicopathological or demographic variable. Oct-4 was expressed only in one case. CONCLUSIONS: CD133 expression was significantly seen higher in Stage III-IV tumors, the stem cells may be responsible for the aggressiveness of the OSCCs and these stem cells can be potential prognostic markers and targets for the future targeted therapy.

Circulating MicroRNA-21 Expression as a Novel Serum Biomarker for Oral Sub-Mucous Fibrosis and Oral Squamous Cell Carcinoma

Background: Circulating miRNAs (miRs) in the biofluids such as serum and plasma act as potential biomarkers for early diagnosis, treatment and prognosis. In the present study, an attempt made to see the expression of miR-21 in serum of 20 cases of Oral sub-mucous fibrosis (OSMF), 20 cases of Oral squamous cell carcinoma and 40 healthy volunteers. The expression of miR-21 was evaluated in relation to different demographical and clinicopathological features such as sex, tobacco, pan-masala, alcohol, smoking and clinical staging respectively with an aim to identify correlation with oral pre-cancer and cancer stages. Materials and Methods: The relative expression level of miR-21 was determined by quantitative real-time RT-PCR (qRT-PCR) in the sera of 20 OSCC, 20 OSMF patients and 40 healthy subjects as a control. Association between expression of miR-21 and OSCC clinical stages and demographical parameters such as sex, pan-masala, tobacco, smoking, alcohol have also been analyzed in detail. Results: The results obtained by t-test revealed significant increase in the expression level of miR-21 in OSCC as compared to OSMF. The study also revealed the positive correlation between higher miR-21 expression and pan-masala chewers as shown by t-test. The statistical test, ANOVA has also indicated a positive correlation between up-regulation of miR-21 in the clinical stages of the OSCC. Conclusion: The results of present study indicated up-regulation of circulating miR-21 in serum of OSCC as compared to OSMF (p=0.001), this study also elucidated the positive correlation between miR-21 expression in OSCC/OSMF patients, only one demographical parameter (Pan-masala) and negative correlation for other parameters such as sex, tobacco, smoking, alcohol etc. Other findings suggested a significant increase (p=0.000) in the expression of miR-21 in clinical staging (I-IV) of oral cancer. More studies are needed to validate it as potential diagnostic and prognostic biomarker for OSMF and OSCC for better management.

Cervical cancer screening in rural India: Status & current concepts.

Cervical carcinoma is one of the most common and dreaded diseases of women, and in India, it accounts for 16 per cent of total cervical cancer cases occurring globally. The situation is more alarming in the rural areas where the majority of women are illiterate and ignorant about the hazards of cervical cancer. Different screening strategies such as rural cancer registries and camp approach for cancer detection have been found useful in minimizing the problem of cervical cancer in the villages. Various screening techniques such as visual inspection with acetic acid, visual inspection with Lugol's iodine, visual inspection with magnification devices-magnavisualizer, Pap smear and HPV-DNA testing have been suggested and tried under low-resource settings of our country, and cervical cytology screening has been found effective in reducing incidence of the disease. In the present review, feasibility of different screening methods has been assessed to find out the most suitable mode applicable at the rural level. Single lifetime screening particularly of high-risk women along with analysis of cost-effective tumour markers such as Argyrophilic nucleolar organizer regions (AgNOR) counts to discriminate high-risk dysplasia cases appears to be an appropriate approach in fighting against cervical cancer.

Cervical Cytopathological Changes Associated with Onset of Menopause.

BACKGROUND: In the life of a woman, after 40 years of age, onset of menopause occurs during which hormonal imbalances take place. The present study is aimed at finding out cytopathological changes in the cervical epithelium associated with this hormonal disturbance. MATERIALS AND METHODS: Cervical cancer screening program is in progress under auspices of Era's Lucknow Medical College and Hospital, Lucknow, since May 2013, in the villages of Lucknow West through camp approach. Till September 2017, 140 camps have been organized and 2440 women attending the camp have been cytologically examined. Out of these, 1534 women were perimenopausal, 165 premenopausal, and 441 postmenopausal. The cytopathological changes have been studied in these three categories of women in relation to different predisposing factors to the cervical carcinogenesis. RESULTS: The squamous intraepithelial lesion (SIL) rate was higher with onset of menopause in the premenopausal women. The SIL rate was higher with nulliparity in these women as well as in the postmenopausal women and also with different gynecological symptoms and clinical lesions of the cervix. The SIL changes associated with HPV and HSV were also higher in them. CONCLUSION: A high SIL rate found with onset of menopause may be the outcome of gradual estrogen withdrawal in the premenopausal women. Hence, cytological evaluation is mandatory in women between 41 and 45 years of age to rule out any occurrence of cervical cytopathology.

Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

INTRODUCTION: MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers. AIM: The present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility. MATERIALS AND METHODS: The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. RESULTS: Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and miRNA 196a2 polymorphisms showed no association with cervical cancer. However, interaction of miRNA polymorphisms with smoking habit showed higher risk of cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no significant modification in the risk of cervical cancer was seen for other polymorphisms. CONCLUSION: The results of the present study demonstrate that, miRNA 499 T/C polymorphism is significantly associated with genetic susceptibility to cervical cancer and may have a role in its pathogenesis.

p53 Codon 72 Gene Polymorphism Studies and p53 Expression by Immunohistochemistry in Oral Lesions as Risk Factor for Malignancy.

BACKGROUND: Wild-type p53 nuclear phosphoproteins are critical cell cycle regulatory tumor-suppressor gene. Genetic mutation of p53 gene is common in several head-neck cancers, usually associated with smoking and human papillomavirus (HPV) infection. In India, instead of HPV, tobacco/pan masala chewing is more commonly associated with oral cancer. AIM: The aim of this study was to investigate p53 codon 72 gene polymorphism and expression of p53 by immunohistochemistry (IHC) in oral lesions as a risk factor for its association with malignancy. MATERIALS AND METHODS: A total of 41 cases of oral lesions comprising 6 cases of leukoplakia and 35 cases of oral squamous cell carcinoma (OSCC), between 30 and 60 years age and tobacco/pan masala chewers were taken. Molecular analysis of p53 codon 72 gene polymorphism was performed by polymerase chain reaction - restriction fragment length polymorphism for Arg/Arg, Arg/Pro, and Pro/Pro. Tissue expression of p53 was done by IHC. RESULTS: Genotype frequencies of 35 carcinoma cases of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 23%, 57%, and 20%, respectively, and six leukoplakia cases of p53 Arg/Arg and Arg/Pro genotype were 50% and 50%, respectively. By IHC for expression of p53 out of 35 cases of OSCC biopsies, 17 (48.57%) had weak staining, 14 cases (40%) showed evidence of p53 protein staining, and four cases (11.42%) showed negative staining. Among six cases of leukoplakia, 3 (50%) showed weak staining and 3 (50%) showed negative results. CONCLUSION: The findings of the study indicate that there is no significant association between p53 codon 72 gene polymorphism with OSCC and leukoplakia associated with tobacco/pan masala chewing.

Single life time cytological screening in high risk women as an economical and feasible approach to control cervical cancer in developing countries like India.

In view of funding crunches and inadequate manpower in cytology in developing countries like India, single lifetime screening for cervical cancer has been suggested. In this study, an attempt was made to identify high risk groups of women for this screening to make it more effective for early detection. Cytological data were derived from the ongoing routine cervical cytology screening program for women attending Gynaecology Out Patient Department of Queen Mary's Hospital of K.G.Medical University, Lucknow, India during a span of 35 years (April 1971 - December 2005). Cervical smears in a total of 38,256 women were cytologically evaluated. The frequencies of squamous intraepithelial lesions of cervix (SIL) and carcinoma cervix were found to be 7.0% and 0.6%, respectively, in the series. Predisposing factors related to cervical carcinogenesis were analyzed in detail to establish the most vulnerable groups of women for single life time screening. The incidence of SIL and carcinoma cervix was found to be maximal in women above the age of 40 years irrespective of parity and in multiparous women (with three or more children) irrespective of age. The incidence of cervical cytopathologies was significantly higher in symptomatic women, the frequency of SIL being alarmingly higher in women complaining of contact bleeding and that of carcinoma cervix in older women with postmenopausal bleeding. It is consequently felt that single life time screening must include the three groups of women delineated above. Such selective screening appears to be the most economical, cost effective and feasible approach to affordably control the menace of cervical cancer in developing countries like India.

An unusual occurrence of multiple epidermoid cysts in both sides of buccal mucosa: A unique and rare first case report.

Intraoral epidermoid cyst of buccal mucosa is generally an uncommon entity. Epidermal inclusion cyst refers sequestration of epidermal elements into the dermal and deeper tissue during the fetal period in line of fusion of embryonic process or acquired due to implantation of the epithelium due to trauma or surgery. It usually presents as slow growing asymptomatic cysts but may be symptomatic due to large size, interfering with mastication and speech or secondary infection. Surgical excision is done for removal of these cysts. We report an interesting case of multiple epidermal cysts in both sides of buccal mucosa in a 35-year-old male patient.

Is the tumor infiltrating natural killer cell (NK-TILs) count in infiltrating ductal carcinoma of breast prognostically significant?

PURPOSE: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. MATERIAL AND METHODS: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. RESULTS: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (χ2=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (χ2=1.60, p>0.05). CONCLUSION: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.

Cisplatin combination chemotherapy induces oxidative stress in advance non small cell lung cancer patients.

BACKGROUND: This study determine oxidative stress and survival prospectively in advanced stage non small cell lung cancer (NSCLC) patients following cisplatin based combination chemotherapy. MATERIALS AND METHODS: The oxidative stress levels (LPO, NO, GSH and SOD) of 144 control subjects and 203 advanced stage (IIIA/IIIB/IV) newly diagnosed NSCLC patients were assessed at pre-treatment (day '0'), and after the 3rd and 6th cycles of chemotherapy. Groups were compared by repeated measures ANOVA while comparison of survival curves was conduced by Kaplan-Meier methods. RESULTS: The pre-treatment mean levels of LPO and NO in patients were significantly (P<0.01) higher while GSH and SOD were significantly (P<0.01) lower as compared to control. The oxidative stress was elevated more significantly (P<0.01) after the chemotherapy and was more evident in higher stage than lower stage patients. The two year overall survival (%) of stage IV patients was significantly lower (P<0.05) as compared to stage III A and III B. The proportional mortality was also maximal in stage IV patients (37.0%) followed by stage III B (31.7%) and III A (20.0%). CONCLUSION: Cisplatin based combination chemotherapy induces oxidative stress in NSCLC patients.

IL-10 -1082 G>A: a risk for prostate cancer but may be protective against progression of prostate cancer in North Indian cohort.

BACKGROUND: Chronic intraprostatic inflammation is suspected to play a major role in the pathogenesis of prostate cancer (PCa). Polymorphisms in interleukin-10 (IL-10), a key anti-inflammatory cytokine gene can influence immune response and immune evasion of tumor cells. Its role as an anti-metastatic molecule is also well documented. METHODS: Gene promoter polymorphisms in IL-10 (-1082 G>A and -819 C>T) was analyzed in 159 PCa patients and 259 healthy controls to investigate their potential association with susceptibility for PCa. RESULTS: Our results indicated that the heterozygous (GA) and homozygous mutant (AA) genotypes of IL-10 -1082 to be more prevalent among PCa patients in comparison to controls (GA: OR - 2.8, p = 0.011; AA: OR - 2.3, p = 0.037). More patients (92.5%) than controls (82.7%) were positive for the A allele (GA + AA: OR - 2.6, p = 0.015). We observed lower frequency of T(-819)-G(-1082) haplotype in patients without bone metastasis (4.4%, OR - 0.30, p = 0.019) in comparison to PCa patients with bone metastasis (12.6%). CONCLUSION: Our results support the emerging hypothesis that genetically determined immune activity may play a role in the pathophysiology of PCa. Our findings of high producer of IL-10 -1082 variants suggest initiation of PCa. Future studies in large cohort of different ethnicity PCa groups are warranted to establish definite associations with other cytokine gene polymorphisms.