Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population

Abstract Background Prostate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namely cytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1). Methods The current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping of CYP1A1 T3801C polymorphisms and GSTM1/GSTT-null was made, respectively, by PCR-RFLP and multiplex PCR. Results No significantly positive associations were found for the CYP1A1 T3801C [p = 0.71, OR = 1.23 (0.56–2.72)] and GSTM1-null [p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association between GSTT1-null genotype [p = 0.03, OR = 2.03 (1.06–3.99)], GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa. Conclusions The risk of developing prostate cancer in Algeria does not appear to be associated with CYP1A1 T3801C genotypes and GSTM1-null, but GSTT1-null and GSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.

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Genetic Variations in Inflammatory Response Genes and Their Association with the Risk of Prostate Cancer

BioMed Research International ◽

10.1155/2015/674039 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Xin Cui ◽

Hao Yan ◽

Tong-Wen Ou ◽

Chun-Song Jia ◽

Qi Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Inflammatory Response ◽

Prostate Cancer Risk ◽

Genetic Variations ◽

Odds Ratios ◽

Comparison Model ◽

Pcr Rflp ◽

Cox 2 ◽

Cox 1

Prostate cancer is a common cancer in men. Genetic variations in inflammatory response genes can potentially influence the risk of prostate cancer. We aimed to examine the association betweenPPARGPro12Ala,NFKB1-94 ins/del,NFKBIA-826C/T,COX-1(50C>T), andCOX-2(-1195G>A) polymorphisms on prostate cancer risk. The genotypes of the polymorphisms were ascertained in 543 prostate cancer patients and 753 controls through PCR-RFLP and the risk association was evaluated statistically using logistic regression analysis. TheNFKB1-94 polymorphism was shown to decrease prostate cancer risk in both heterozygous and homozygous comparison models (odds ratios of 0.74 (95% CI = 0.58–0.96) (P=0.02) and 0.57 (95% CI = 0.42–0.78) (P<0.01), resp.). An opposite finding was observed forCOX-2(-1195) polymorphism (odds ratios of 1.58 (95% CI = 1.15–2.18) (P<0.01) for heterozygous comparison model and 2.08 (95% CI = 1.48–2.92) (P<0.01) for homozygous comparison model). No association was observed for other polymorphisms. In conclusion,NFKB1-94 ins/del andCOX-2(-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.

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Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.4935 ◽

2017 ◽

Vol 35 (20) ◽

pp. 2240-2250 ◽

Cited By ~ 69

Author(s):

Julie Lecarpentier ◽

Valentina Silvestri ◽

Karoline B. Kuchenbaecker ◽

Daniel Barrowdale ◽

Joe Dennis ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

Risk Scores ◽

Cancer Risks ◽

Prostate Cancer Susceptibility ◽

Common Genetic Variants ◽

Breast And Prostate Cancer ◽

Male Carriers

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

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METHYLENETETRAHYDROFOLATE REDUCTASE C677T GENE POLYMORPHISM AND PROSTATE CANCER RISK

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i5.24390 ◽

2018 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Samah Tellouche-bouhouhou ◽

Djalila Chellat-rezgoune ◽

Noureddine Abadi ◽

Dalila Satta ◽

Abderrezak Dahdouh

Keyword(s):

Prostate Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

Mthfr C677t ◽

Mthfr Gene ◽

Single Nucleotide ◽

Mthfr C677t Polymorphism ◽

Increased Risk ◽

Significant Difference

Objective: The single nucleotide polymorphism C677T of the methylenetetrahydrofolate reductase (MTHFR) gene encodes a thermolabile enzyme. This polymorphism was found to be implicated in cancer susceptibility. In this study, we analyzed the distribution of the MTHFR C677T polymorphism in two cohorts; patients and controls native of East of Algeria to explore the possible association between this polymorphism and prostate cancer susceptibility.Methods: Our examination has been conducted in 98 cases and 98 healthy controls. Genotyping was realized by polymerase chain reaction-restriction fragment length polymorphism method.Results: Compared with CC homozygous, the CT heterozygous was found to have a significantly increased risk of prostate cancer (p=0.04; odds ratio [OR]=2.01, 95% confidence interval [CI]: 1.02–3.95). However, no statistically significant difference was observed concerning the TT homozygous (p=0.74; OR=1.25, 95% CI: 0.51–3.04).Conclusion: Our results indicate that the genotype CT is a risk factor for prostate cancer in East of Algeria.

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Prevalence of the Ser217Leu Variant of the ELAC2 Gene and Its Association with Prostate Cancer in Population of the Littoral Region of Cameroon

Prostate Cancer ◽

10.1155/2019/5974928 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Alexandra Lindsey Zune Djomkam ◽

Theodore Beyeme Sala ◽

Clarisse Baari Memba ◽

Dieudonné Lemuh Njimoh

Keyword(s):

Prostate Cancer ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Salting Out ◽

Littoral Region ◽

Increased Risk ◽

Pcr Rflp ◽

Study Population ◽

Sporadic Cases ◽

Human Genomic

Background. HPC2/ELAC2 has been identified as a prostate cancer (PC) susceptibility gene. Ser- Leu changes at amino acid 217 have been one of the most studied variants of this gene. Several reports have shown association of this variant with PC in samples of men drawn from families with hereditary PC and even sporadic cases. Aim. This study aimed at assessing this association and the prevalence of the Ser217Leu variant of ELAC2 in populations of the Littoral Region of Cameroon. Method. 103 PC case subjects and 80 randomly selected controls identified from the study population participated in the study. 2 milliliters of blood samples was collected from each of the consented participants and used for human genomic DNA extraction and genotyping of the ELAC2 gene by the nonenzymatic salting out and PCR-RFLP methods, respectively. Results. The frequencies of the wild type (SS), heterozygous mutant (SL), and homozygous mutant (LL) genotypes were, respectively, 28.2%, 49.5%, and 22.3% in prostate cancer patients and 28.8%, 67.5%, and 3.7% in controls. Comparing the LL with SS and (SL+LL) with SS showed that the presence of two copies of the L allele confers a high risk of prostate cancer as compared to the presence of only one L allele which presents no risk of prostate cancer (OR = 6.080 and 1.030, respectively). Analysis of our results also suggested an association (P = 0.0012) of the Ser217Leu variant with increased risk of prostate cancer. Conclusion. Alterations in the ELAC2 gene contribute to prostate cancer susceptibility in men living in the Littoral Region of Cameroon.

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Polymorphisms of Homologous RecombinationRAD51,RAD51B,XRCC2, andXRCC3Genes and the Risk of Prostate Cancer

Analytical Cellular Pathology ◽

10.1155/2015/828646 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Maria Nowacka-Zawisza ◽

Ewelina Wiśnik ◽

Andrzej Wasilewski ◽

Milena Skowrońska ◽

Ewa Forma ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Repair ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Critical Role ◽

Prostate Cancer Risk ◽

Nucleotide Polymorphisms ◽

Repair Capacity ◽

Dna Repair Capacity ◽

Risk Of Cancer

Genetic polymorphisms in DNA repair genes may induce individual variations in DNA repair capacity, which may in turn contribute to the risk of cancer developing. Homologous recombination repair (HRR) plays a critical role in maintaining chromosomal integrity and protecting against carcinogenic factors. The aim of the present study was to evaluate the relationship between prostate cancer risk and the presence of single nucleotide polymorphisms (SNPs) in the genes involved in HRR, that is,RAD51(rs1801320 and rs1801321),RAD51B(rs10483813 and rs3784099),XRCC2(rs3218536), andXRCC3(rs861539). Polymorphisms were analyzed by PCR-RFLP and Real-Time PCR in 101 patients with prostate adenocarcinoma and 216 age- and sex-matched controls. A significant relationship was detected between theRAD51gene rs1801320 polymorphism and increased prostate cancer risk. Our results indicate that theRAD51gene rs1801320 polymorphism may contribute to prostate cancer susceptibility in Poland.

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Links between genetic and environmental factors and prostate cancer risk

The Prostate ◽

10.1002/(sici)1097-0045(19990601)39:4<262::aid-pros6>3.0.co;2-p ◽

1999 ◽

Vol 39 (4) ◽

pp. 262-268 ◽

Cited By ~ 25

Author(s):

Peter Ekman ◽

Henrik Gr�nberg ◽

Hideyasu Matsuyama ◽

Merja Kivineva ◽

Ulf S.R. Bergerheim ◽

...

Keyword(s):

Prostate Cancer ◽

Environmental Factors ◽

Cancer Risk ◽

Prostate Cancer Risk ◽

Genetic And Environmental Factors

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Breast and prostate cancer risk: the interplay of polygenic risk, high-impact monogenic variants, and family history

10.1101/2021.06.04.21258277 ◽

2021 ◽

Author(s):

Emadeldin Hassanin ◽

Patrick May ◽

Rana Aldisi ◽

Isabel Spier ◽

Andreas J. Forstner ◽

...

Keyword(s):

Prostate Cancer ◽

Family History ◽

Cancer Risk ◽

Cumulative Incidence ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

High Impact ◽

Polygenic Risk ◽

Cancer Susceptibility Genes ◽

Breast And Prostate Cancer

Purpose Investigate to which extent polygenic risk scores (PRS), high-impact monogenic variants, and family history affect breast and prostate cancer risk by assessing cancer prevalence and cancer cumulative lifetime incidence. Methods 200,643 individuals from the UK Biobank were stratified as follows: 1. carriers or non-carriers of high impact constitutive, monogenic variants in cancer susceptibility genes, 2. high or non-high PRS (90th percentile threshold), 3. with or without a family history of cancer. Multivariable logistic regression was used to compare the odds ratio (OR) across the different groups while Cox proportional hazards models were used to compute the cumulative incidence through life. Results Breast and prostate cancer cumulative incidence by age 70 is 7% and 5% for non-carriers with non-high PRS and reaches 37% and 32% among carriers of high-impact variants in cancer susceptibility genes with high PRS. The additional presence of family history is associated with a further increase of the risk of developing cancer reaching an OR of 14 and 21 for breast and prostate cancer, respectively. Conclusion High PRS confers a cancer risk comparable to high-impact monogenic variants. Family history, monogenic variants, and PRS contribute additively to breast and prostate cancer risk.

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Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.620690 ◽

2021 ◽

Vol 8 ◽

Author(s):

Veljko Santric ◽

Dejan Dragicevic ◽

Marija Matic ◽

Milica Djokic ◽

Marija Pljesa-Ercegovac ◽

...

Keyword(s):

Prostate Cancer ◽

Glutathione Transferase ◽

Redox Homeostasis ◽

Prostate Cancer Risk ◽

Gst Polymorphisms ◽

Increased Risk ◽

Genes Encoding ◽

Gst Polymorphism ◽

First Time

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs’ role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.

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Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer?

Cancers ◽

10.3390/cancers13215464 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5464

Author(s):

Klaudia Stempa ◽

Dominika Wokołorczyk ◽

Wojciech Kluźniak ◽

Emilia Rogoża-Janiszewska ◽

Karolina Malińska ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Prostate Cancer Risk ◽

Breast Cancer Susceptibility ◽

Elevated Risk ◽

Breast Cancer Susceptibility Gene ◽

Gene Panels

The current cancer testing gene panels tend to be comprehensive rather than site-specific. BARD1 is one of the genes commonly included in the multi-cancer testing panels. Mutations in BARD1 confer an increase in the risk for breast cancer, but it is not studied whether or not they predispose to prostate cancer. To establish if BARD1 mutations also predispose to prostate cancer, we screened BARD1 in 390 Polish patients with hereditary prostate cancer. No truncating mutations were identified by sequencing. We also genotyped 5715 men with unselected prostate cancer, and 10,252 controls for three recurrent BARD1 variants, including p.Q564X, p.R658C and p.R659=. Neither variant conferred elevated risk of prostate cancer (ORs between 0.84 and 1.15, p-values between 0.57 and 0.93) nor did they influence prostate cancer characteristics or survival. We conclude that men with a BARD1 mutation are not at elevated prostate cancer risk. It is not justified to inform men about increased prostate cancer risk in case of identification of a BARD1 mutation. However, a female relative of a man with a BARD1 mutation may benefit from this information and be tested for the mutation, because BARD1 is a breast cancer susceptibility gene.

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