No association of breast cancer risk with integrin beta3 (ITGB3) Leu33Pro genotype

Bojesen, Stig E.; Tybjærg‐Hansen, Anne; Axelsson, C. K.; Nordestgaard, Børge G.

doi:10.1038/sj.bjc.6602674

Cited by 10 publications

(4 citation statements)

References 13 publications

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“…Among the participating COGS studies, the TL had been determined in cases and controls from the UK Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) study ( 13 , 28 ) ( ) controls from the Danish Copenhagen City Heart study ( 28 , 42 , 43 ) (CCHS) and breast cancer cases from the Copenhagen General Population Study ( 18 , 44 ) (CGPS). TL was measured using a real-time PCR methodology as described elsewhere ( 11 – 13 , 45 , 46 ) and a composite variable, putting the SEARCH, CCHS and CGPS data onto the same scale, was used for all analyses ( 28 ) (see Supplementary Material ).…”

Section: Methodsmentioning

confidence: 99%

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

Pooley¹,

Bojesen

Weischer

et al. 2013

Human Molecular Genetics

132

159

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Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the “iCOGS” custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10−10) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10−7) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10−14) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10−4) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.

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Section: Methodsmentioning

confidence: 99%

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

Pooley¹,

Bojesen

Weischer

et al. 2013

Human Molecular Genetics

132

159

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“…In down-regulated interactions, one gene interaction groups were found. Of the hub genes, ITGB3(integrin beta 3) acts as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells (Lei et al, 2011), and it also plays roles in breast cancer and non-small-cell lung cancer (Bojesen et al, 2005;Ni et al, 2015). Though there were no functional reports of theses hub genes on TCC，these hub genes may play potential regulatory roles in TCC and our future study will focus on them.…”

Section: Discussionmentioning

confidence: 99%

An integrated analysis of mRNA-miRNA transcriptome data revealed hub regulatory networks in three genitourinary cancers

Liu¹,

Zhang²

2018

Biocell

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Bladder, kidney, prostate and testicular carcinoma are the top four genitourinary cancers in China. Here we analyzed mRNA and miRNA expression profiles of carcinomas of the bladder (TCC), kidney (ccRCC) and testis (TGCT) to uncover their specific regulatory mechanisms. The gene expression profiles of GSE31617 were downloaded from GEO database, which contained 27 samples, including 10 TCC, 7 TGCT and 10 ccRCC. Specific up-and downregulated differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) of each cancer were selected and target genes of DEmiRNAs were predicted. Gene interaction network of the shared genes and target genes of DEmiRNAs of each cancer was predicted by STRING and constructed by Cytoscape. In each cancer, we build regulatory networks of hub genes selected and conducted GO analysis of enriched genes. Furthermore, we chose four hub genes (SALL4, RHEB,CDC42 and TNN) for survival analysis in OncoLnc database, and they all had effects on the survival rate of another genitourinary cancer-kidney renal clear cell carcinoma (KIRC). In conclusion, the present study indicated that the identified hub genes promote our understanding of molecular mechanisms underlying the development of three genitourinary cancers, and might be used as molecular targets and diagnostic biomarkers for the treatment of them.

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“…One study reported an association between the homozygous 33Leu genotype and breast cancer risk [38], other studies suggested that the 33Pro allele is associated with breast cancer risk [36, 37, 39], and others reported no associations [40, 41]. An association of ITGB3 Leu33Pro was reported with ovarian cancer in the general population [43], but this was not confirmed in any other study [42].…”

Section: Discussionmentioning

confidence: 99%

“…A number of epidemiological studies have suggested associations of the ITGB3 Leu33Pro with the risk of developing cancers including non-Hodgkin lymphoma [34], colon [34], kidney [35], breast [36-41] and ovarian cancer [36, 42, 43]. However, little data exist on the influence of this polymorphism on breast and ovarian cancer risk for women with BRCA1 or BRCA2 mutations.…”

Section: Introductionmentioning

confidence: 99%

The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers

Jakubowska

Rozkrut

Antoniou

et al. 2009

Breast Cancer Res Treat

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Integrins containing the β3 subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the β3 subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the ITGB3 polymorphism was associated with an increased risk of ovarian cancer for BRCA1 mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00–1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96–1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for BRCA2 mutation carriers (HR 1.09, 95% CI 0.89–1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

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No association of breast cancer risk with integrin beta3 (ITGB3) Leu33Pro genotype

Cited by 10 publications

References 13 publications

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

An integrated analysis of mRNA-miRNA transcriptome data revealed hub regulatory networks in three genitourinary cancers

The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers

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