Association of 8q24.21 loci with the risk of colorectal cancer: A systematic review and meta‐analysis

Haerian, Monir Sadat; Baum, Larry; Haerian, Batoul Sadat

doi:10.1111/j.1440-1746.2011.06831.x

Cited by 24 publications

(22 citation statements)

References 45 publications

(139 reference statements)

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“…Among the polymorphisms in block 4 (region 3) at 8q24, rs6983267 has been consistently identified in many studies, with an OR ranging from 0.65 to 1.42 [46], [47], [49]–[51], [57], [59], [81], [82], therefore the strongest association with PCa risk in this LD block [53], [83]. It has also been associated with CRC and ovarian cancer [76].…”

Section: Discussionmentioning

confidence: 97%

Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

et al. 2012

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BackgroundProstate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations.MethodsTo identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ2-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r2>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays.ResultsThe GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction.ConclusionPooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.

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Section: Discussionmentioning

confidence: 97%

Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

et al. 2012

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“…Two SNPs within 1q41 (rs6687758 and rs6691170) were shown to be in linkage disequilibrium with a single imputed SNP [19], and we therefore excluded rs6691170. Three SNPs within 8q24.21 (rs10505477, rs6983267 and rs7014346) had a D prime of 1.0, and based on the results of a meta-analysis [20], we excluded rs10505477 and rs7014346. Three of the SNPs are within 15q31 (rs11632715, rs16969681 and rs4779584), but because only two were associated with colorectal cancer in a multivariable model [21], we excluded rs4779584.…”

Section: Resultsmentioning

confidence: 99%

Quantifying the Utility of Single Nucleotide Polymorphisms to Guide Colorectal Cancer Screening

et al. 2016

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Aim:To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. Methods: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. Results: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. Conclusion: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories.

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“…The chromosomal locus 8q24 is one of the most frequently amplified and altered regions in a variety of cancer types, including ovarian [13], colorectal [14–17], breast [18–22], prostate [23–28], and others. The 8q24.21 locus is particularly attractive, in part attributable to its containment of the most commonly amplified gene in cancer, MYC.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of FAM84B during prostate cancer progression

Wong

Kapoor

et al. 2017

Oncotarget

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Although the FAM84B gene lies within chromosome 8q24, a locus frequently altered in prostate cancer (PC), its alteration during prostate tumorigenesis has not been well studied. We report here FAM84B upregulation in DU145 cell-derived prostate cancer stem-like cells (PCSLCs) and DU145 cell-produced lung metastases compared to subcutaneous xenograft tumors. FAM84B protein was detected in bone metastases and primary PCs. Nanostring examination of 7 pairs of tumor adjacent normal and PC tissues revealed elevations in FAM84B mRNA levels in all carcinomas. Furthermore, through analysis of FAM84B expression using large datasets within the Gene Expression Omnibus and OncomineTM database, we demonstrate significant increases in FAM84B mRNA in 343 primary PCs versus 181 normal tissues, and elevations in the FAM84B gene copy number (GCN) in 171 primary PCs versus 61 normal tissues. While FAM84B was not detected at higher levels via immunohistochemistry in high grade (Gleason score/GS 8-10) tumors compared to GS6-7 PCs, analyses of FAM84B mRNA and GCN using datasets within the cBioPortal database demonstrated FAM84B upregulation in 12% (67/549) of primary PCs and 18% (73/412) of metastatic castration resistant PCs (mCRPCs), and GCN increases in 4.8% (26/546) of primary PCs and 26% (121/467) of mCRPCs, revealing an association of the aforementioned changes with CRPC development. Of note, an increase in FAM84B expression was observed in xenograft CRPCs produced by LNCaP cells. Furthermore, FAM84B upregulation and GCN increases correlate with decreases in disease free survival and overall survival. Collectively, we demonstrate a novel association of FAM84B with PC tumorigenesis and CRPC progression.

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Association of 8q24.21 loci with the risk of colorectal cancer: A systematic review and meta‐analysis

Abstract: Our data suggested that the rs6983267 G > T polymorphism is a risk factor for CRC in Asians, Europeans, and Americans with European ancestry.

Cited by 24 publications

References 45 publications

Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

Quantifying the Utility of Single Nucleotide Polymorphisms to Guide Colorectal Cancer Screening

Upregulation of FAM84B during prostate cancer progression

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