Single nucleotide polymorphisms and prostate cancer susceptibility.
Ontology highlight
ABSTRACT:
SUBMITTER: Loeb S
PROVIDER: S-EPMC2615108 | biostudies-literature | 2008
REPOSITORIES: biostudies-literature
Publications
Single nucleotide polymorphisms and prostate cancer susceptibility.
Reviews in urology 20080101 4
Similar Datasets
Project description:A large number of genes associated with various cancer types contain single nucleotide polymorphisms (SNPs). SNPs are located in gene promoters, exons, introns as well as 5'- and 3'- untranslated regions (UTRs) and affect gene expression by different mechanisms. These mechanisms depend on the role of the genetic elements in which the individual SNPs are located. Moreover, alterations in epigenetic regulation due to gene polymorphisms add to the complexity underlying cancer susceptibility related to SNPs. In this systematic review, we discuss the various genetic and epigenetic mechanisms involved in determining cancer susceptibility related to various SNPs located in different genetic elements. We also discuss the diagnostic potential of these SNPs and the focus for future studies.
| S-EPMC5746410 | biostudies-literature
Project description:Thyroid cancer (TC) is the most common endocrine malignancy and its incidence continues to rise worldwide. Ionizing radiation exposure is the best established etiological factor. Heritability is high; however, despite valuable contribution from recent genome-wide association studies, the current understanding of genetic susceptibility to TC remains limited. Several studies suggest that altered function or expression of the DNA mismatch repair (MMR) system may contribute to TC pathogenesis. Therefore, the present study aimed to evaluate the potential role of a panel of MMR single nucleotide polymorphisms (SNPs) on the individual susceptibility to well-differentiated TC (DTC). A case-control study was performed involving 106 DTC patients and 212 age- and gender-matched controls, who were all Caucasian Portuguese. Six SNPs present in distinct MMR genes (MLH1 rs1799977, MSH3 rs26279, MSH4 rs5745325, PMS1 rs5742933, MLH3 rs175080 and MSH6 rs1042821) were genotyped through TaqMan® assays and genotype-associated risk estimates were calculated. An increased risk was observed in MSH6 rs1042821 variant homozygotes [adjusted odds ratio (OR)=3.42, 95% CI: 1.04-11.24, P=0.04, under the co-dominant model; adjusted OR=3.84, 95% CI: 1.18-12.44, P=0.03, under the recessive model]. The association was especially evident for the follicular histotype and female sex. The association was also apparent when MSH6 was analysed in combination with other MMR SNPs such as MSH3 rs26279. Interestingly, two other SNP combinations, both containing the MSH6 heterozygous genotype, were associated with a risk reduction, suggesting a protective effect for these genotype combinations. These data support the idea that MMR SNPs such as MSH6 rs1042821, alone or in combination, may contribute to DTC susceptibility. This is coherent with the limited evidence available. Nevertheless, further studies are needed to validate these findings and to establish the usefulness of these SNPs as genetic susceptibility biomarkers for DTC so that, in the near future, cancer prevention policies may be optimized under a personalized medicine perspective.
| S-EPMC5876466 | biostudies-literature
Project description:BACKGROUND:Prostate cancer is one of the most common cancers in men. LIM kinase1 (LIMK1) is a mediator in the process of cytoskeleton reorganization and cell motility. LIMK1 is related to progression, invasiveness and metastases of prostate cancer. However, the relationship between LIMK1 single nucleotide polymorphism (SNP) and the risk of prostate cancer has not been studied. AIM:The aim of our study is to determine the association between LIMK1 polymorphisms and the risk of prostate in a Chinese population. METHODS:This case-control study consisted of 162 prostate cancer patients and 187 healthy control subjects. Five SNPs of LIMK1 including rs2269082, rs2269081, rs178409, rs6460071 and rs710968 were genotyped using iPLEX genotyping assays on a MassARRAY® platform. RESULTS:No significant relationships were found between polymorphisms genotypes and the risk of prostate cancer. Also, no significant associations were found between genotypes and the individual factors such as Gleason Score, alcohol and cigarette consuming statuses. CONCLUSION:These polymorphisms of LIMK1 were not significantly associated with prostate cancer susceptibility in Chinese men.
| S-EPMC6965917 | biostudies-literature
Project description:Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a 2-3-fold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Although the suggestion of linkage has been reported for many chromosomes, the most promising regions have been difficult to replicate. In this study, we compare genome linkage scans using microsatellites with those using single-nucleotide polymorphisms (SNPs), performed in 467 men with prostate cancer from 167 families. For the microsatellites, the ABI Prism Linkage Mapping Set version 2, with 402 microsatellite markers, was used, and, for the SNPs, the Early Access Affymetrix Mapping 10K array was used. Our results show that the presence of linkage disequilibrium (LD) among SNPs can lead to inflated LOD scores, and this seems to be an artifact due to the assumption of linkage equilibrium that is required by the current genetic-linkage software. After excluding SNPs with high LD, we found a number of new LOD-score peaks with values of at least 2.0 that were not found by the microsatellite markers: chromosome 8, with a maximum model-free LOD score of 2.2; chromosome 2, with a LOD score of 2.1; chromosome 6, with a LOD score of 4.2; and chromosome 12, with a LOD score of 3.9. The LOD scores for chromosomes 6 and 12 are difficult to interpret, because they occurred only at the extreme ends of the chromosomes. The greatest gain provided by the SNP markers was a large increase in the linkage information content, with an average information content of 61% for the SNPs, versus an average of 41% for the microsatellite markers. The strengths and weaknesses of microsatellite versus SNP markers are illustrated by the results of our genome linkage scans.
| S-EPMC1182157 | biostudies-literature
Project description:The specific causes of prostate cancer are not known. However, multiple etiologic factors, including genetic profile, metabolism of steroid hormones, nutrition, chronic inflammation, family history of prostate cancer, and environmental exposures are thought to play significant roles. Variations in exposure to these risk factors may explain interindividual differences in prostate cancer risk. However, regardless of the precise mechanism(s), a robust DNA repair capacity may mitigate any risks conferred by mutations from these risk factors. Numerous single nucleotide polymorphisms (SNPs) in DNA repair genes have been found, and studies of these SNPs and prostate cancer risk are critical to understanding the response of prostate cells to DNA damage. A few SNPs in DNA repair genes are associated with significantly increased risk of prostate cancer; however, in most cases, the effects are moderate and often depend upon interactions among the risk alleles of several genes in a pathway or with other environmental risk factors. This report reviews the published epidemiologic literature on the association of SNPs in genes involved in DNA repair pathways and prostate cancer risk.
| S-EPMC3968564 | biostudies-literature
Project description:BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student's t-test, a χ2 test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.
| S-EPMC8025117 | biostudies-literature
Project description:Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC.
| S-EPMC2661781 | biostudies-literature
Project description:BackgroundSingle-nucleotide polymorphisms (SNPs) in enzyme-coding genes play a role in susceptibility to anti-cancer therapy.Materials & methodsA prospective study was performed of the relationship between enzyme activity and treatment response, drug toxicity and hypersensitivity reactions in 51 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. SNP analysis was performed in 22 enzyme-coding genes with a previously described role in treatment efficacy.ResultsSLC6 and MTHR enzyme activity was related with rates of progressive disease, GSTP1 activity with anti-EGFR antibodies-related skin toxicity, CYP3A5 and MTHR with chemotherapy dose reduction, CYP2B6, IL10, MTHR and TYMS activity with the risk of drug hypersensitivity reactions.ConclusionPharmacogenetics is a valuable predictive marker in oncology, related to chemotherapy treatment response, toxicity and hypersensitivity.
| S-EPMC11587850 | biostudies-literature
Project description:ObjectiveThe purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI).MethodsSeven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls; then, the association with clinicopathological characteristics, BMI, molecular subtype, TNM (T, tumor; N, lymph node; M, metastasis) staging and lymph node status was determined by unconditional logistic regression.ResultsRs12951053 in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m2 group (OR=1.50, 95% CI: 1.02-2.21, P=0.041 and OR=1.92, 95% CI: 1.13-3.26, P=0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5≤BMI<25 kg/m2 group. Rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple-negative breast cancer (OR=1.50, 95% CI: 1.05-2.15, P=0.026 and OR=2.13, 95% CI: 1.05-4.29, P=0.032, respectively), but three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed a negative association with both luminal B and triple-negative breast cancer. The tSNP rs2299941 in PTEN also exhibited a negative association with each molecular subtype, except triple-negative breast cancer. The majority of tSNPs displayed a negative association with stage II or III breast cancer. Most tSNPs showed a negative association with breast cancer that was lymph node negative or with 1-3 positive nodes. Only rs12951053 in TP53 displayed a positive association with lymph node-negative breast cancer (OR=1.43, 95% CI: 1.08-1.91, P=0.013).ConclusionThe majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.
| S-EPMC7896729 | biostudies-literature
Project description:BackgroundLet-7 is a microRNA (miRNA) that targets the β2 adrenergic receptor (ADRB2), hypoxia inducible factor 1 subunit alpha inhibitor (HIF1AN), and claudin 12 (CLDN12) genes. Single nucleotide polymorphisms (SNPs) in the structural or regulatory regions of these miRNA let-7-related genes may be associated with breast cancer carcinogenesis and prognosis. Low let-7 expression may increase breast cancer risk. We investigated the effects of let-7-related gene SNP (mirSNPs) on breast cancer risk and clinical outcomes.MethodsThe distribution frequencies of the three SNPs were genotyped in patients with breast cancer and controls. Multivariate logistic regression analysis was used to evaluate the association between the SNPs and susceptibility to breast cancer. We investigated the effects of these mirSNPs prospectively on disease-free survival (DFS) using the Kaplan-Meier method and the extended multivariate Cox model.ResultsWe found that rs1042713 in the ADRB2 gene and rs11292 in the 3'-UTR of the HIF1AN gene were associated with breast cancer susceptibility (P<0.05). The CLDN12 rs1017105 genotype was associated with estrogen receptor (P=0.031) and progesterone receptor status (P=0.007). The number of risk alleles was associated with estrogen receptor (P=0.034) status in breast cancer patients. In the survival analysis, the extended Cox model demonstrated that rs1042713 (P=0.000) and rs1017105 (P=0.004) were independent predictors of DFS. The number of risk alleles of the ADRB2, HIF1AN, and CLDN12 genes was an independent predictor of DFS (P<0.001).ConclusionLet-7-related mirSNPs might be associated with carcinogenesis and clinical outcome in breast cancer, suggesting that variants of miRNA let-7-related gene networks coregulate breast cancer characteristics.
| S-EPMC6456510 | biostudies-literature