scholarly journals Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers

2012 ◽  
Vol 30 (17) ◽  
pp. 2157-2162 ◽  
Author(s):  
Ju-Hyun Park ◽  
Mitchell H. Gail ◽  
Mark H. Greene ◽  
Nilanjan Chatterjee
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Ovarian Cancer ◽  
Single Nucleotide Polymorphisms ◽  
False Positive ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Thresholds

Purpose To estimate the likely number and predictive strength of cancer-associated single nucleotide polymorphisms (SNPs) that are yet to be discovered for seven common cancers. Methods From the statistical power of published genome-wide association studies, we estimated the number of undetected susceptibility loci and the distribution of effect sizes for all cancers. Assuming a log-normal model for risks and multiplicative relative risks for SNPs, family history (FH), and known risk factors, we estimated the area under the receiver operating characteristic curve (AUC) and the proportion of patients with risks above risk thresholds for screening. From additional prevalence data, we estimated the positive predictive value and the ratio of non–patient cases to patient cases (false-positive ratio) for various risk thresholds. Results Age-specific discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of patients in the highest decile of population risk ranged from 16.2% for ovarian cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were 241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast cancer in women age 50 to 54 or 40 to 44 years, respectively. Conclusion Foreseeable common SNP discoveries may not permit identification of small subsets of patients that contain most cancers. Usefulness of screening could be diminished by many false positives. Additional strong risk factors are needed to improve risk discrimination.

scholarly journals Single Nucleotide Polymorphisms Associated With Prostate Cancer Development in Saudi Males

2020 ◽  
Author(s):  
Awad Osman ◽  
Atif Ali Ahmed ◽  
Asim Ali Elbagir
Keyword(s):  
Prostate Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Association Studies ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Fixed Tissue ◽  
Single Nucleotide ◽  
Nodular Hyperplasia ◽  
Normal Controls

Abstract Background: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PC). In this study, we investigated a group of SNPs in Saudi individuals and compared their frequency in patients and healthy normal controls. Methods: A total of 320 individuals were included in the study: 85 with PC, 120 with benign nodular hyperplasia, and 115 healthy normal controls. DNA was extracted from paraffin-embedded formalin-fixed tissue from PC and nodular hyperplasia patients and from whole blood of healthy controls. A total of thirteen SNPs were genotyped using the TaqMan® MGB PCR assay. Results: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequencies in PC patients than in controls (p < 0.05). The C/A genotype of the rs16901979 SNP was observed significantly more frequently in PC patients than in controls (43% vs 14%, OR = 0.2, p value = 0.0001) and more frequently in PC patients than in the benign hyperplasia group (43% vs 25%, OR = 2.3, p value = 0.03). Conclusion: Our study highlighted several SNP genotypes associated with PC development in Saudi males. These findings have important implications for diagnosing PC and screening unaffected family members of Saudi patients.

scholarly journals Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Lijun Wu ◽  
Liwang Gao ◽  
Xiaoyuan Zhao ◽  
Meixian Zhang ◽  
Jianxin Wu ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Multiple Testing ◽  
Association Studies ◽  
Statistical Significance ◽  
Additive Model ◽  
Recessive Model ◽  
Chinese Children ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P=0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

The Molecular Mechanisms of Estrogen Receptor α on Two Single Nucleotide Polymorphisms to Regulate WNT Signaling in Osteoblasts

2021 ◽  
Author(s):  
◽  
Sarocha Suthon ◽  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Association Studies ◽  
Wnt Signaling Pathway ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Osteoporosis is the most common bone metabolic disorder, affecting over 200 million people globally. It is characterized by bone mass depletion and microarchitectural deterioration, leading to bone fragility and susceptibility to bone fracture. Genetic factors, estrogen deficiency, and dysregulation of the WNT signaling pathway contribute to the development of this disease. Genome-wide association studies have predicted that the single nucleotide polymorphisms (SNPs) rs2887571 and rs9921222 associate with low bone mass, but the mechanism of these SNPs has remained unknown. Analysis of osteoblasts from 112 different joint replacement patients reveals that the genotype of rs2887571 correlates with WNT5B expression, and the genotype of rs9921222 correlates with AXIN1 expression. Mechanistically, SNP rs2887571 has less binding of ERα and NFATc1 to allele A than allele G, resulting in more expression of WNT5B in homozygous AA than homozygous GG. Furthermore, WNT5B exhibits distinct effects from other WNTs on osteoblastogenesis. WNT5B increases mesenchymal stem cell proliferation, promotes adipogenesis, and suppresses osteoblast differentiation via ROR1/2, then activates DVL2/3, Rac1/Cdc42, JNK, and SIN3A signaling, as well as inhibits ROCK2 and β-catenin activity. For SNP rs9921222, homozygous TT has a higher expression of AXIN1 than homozygous CC. Molecular analysis shows that GATA4 favors binding at rs9921222 allele T to promote AXIN1 expression; in contrast, ERα prefers to bind at allele C to suppress the expression, resulting in more expression of AXIN1 in homozygous TT than homozygous CC. Functionally, the level of AXIN1 negatively correlates with the level of active β-catenin, which enhances osteoblast differentiation. Taken together, the biological mechanisms of SNPs rs2887571 and rs9921222, which are associated with osteoporosis via the WNT signaling pathway, are revealed, as well as the inhibitory effect of WNT5B on osteoblastogenesis. These data will be the fundamental knowledge for the development of osteoporosis prediction and therapeutic strategies.

Detecting associated single-nucleotide polymorphisms on the X chromosome in case control genome-wide association studies

2014 ◽  
Vol 26 (2) ◽  
pp. 567-582 ◽  
Author(s):  
Zhongxue Chen ◽  
Hon Keung Tony Ng ◽  
Jing Li ◽  
Qingzhong Liu ◽  
Hanwen Huang
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
X Chromosome ◽  
Association Studies ◽  
Statistical Tests ◽  
Real Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide

In the past decade, hundreds of genome-wide association studies have been conducted to detect the significant single-nucleotide polymorphisms that are associated with certain diseases. However, most of the data from the X chromosome were not analyzed and only a few significant associated single-nucleotide polymorphisms from the X chromosome have been identified from genome-wide association studies. This is mainly due to the lack of powerful statistical tests. In this paper, we propose a novel statistical approach that combines the information of single-nucleotide polymorphisms on the X chromosome from both males and females in an efficient way. The proposed approach avoids the need of making strong assumptions about the underlying genetic models. Our proposed statistical test is a robust method that only makes the assumption that the risk allele is the same for both females and males if the single-nucleotide polymorphism is associated with the disease for both genders. Through simulation study and a real data application, we show that the proposed procedure is robust and have excellent performance compared to existing methods. We expect that many more associated single-nucleotide polymorphisms on the X chromosome will be identified if the proposed approach is applied to current available genome-wide association studies data.

Association betweenCYP1A2gene single nucleotide polymorphisms and clinical responses to clozapine in patients with treatment-resistant schizophrenia

2013 ◽  
Vol 25 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Anto P. Rajkumar ◽  
B. Poonkuzhali ◽  
Anju Kuruvilla ◽  
Alok Srivastava ◽  
Molly Jacob ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Clinical Response ◽  
Treatment Response ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Treatment Resistant ◽  
Single Nucleotide ◽  
Clinical Responses

ObjectivesDespite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role ofCYP1A2gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS.MethodsWe evaluated four single nucleotide polymorphisms (SNP) in theCYP1A2gene, clinical responses and serum clozapine levels in 101 consecutive patients with TRS on stable doses of clozapine. We defined clozapine responsea prioriand investigated allelic and genotypic associations. We assessed the socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition and disability of the participants, using standard assessment schedules for appropriate multivariate analyses.ResultsOur results revealed thatCYP1A2gene SNP (*1C, *1D, *1Eand*1F) were not associated with clozapine treatment response, adverse effects, serum clozapine levels or with disability (pvalues > 0.10).ConclusionAsCYP1A2gene SNP do not help to predict the clinical response to clozapine, routine screening for them prior to start clozapine is currently unwarranted. We suggest future longitudinal genome-wide association studies investigating clinical and pharmacogenetic variables together.

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