Genome-wide association study identifies five new breast cancer susceptibility loci

Turnbull, Clare; Ahmed, Shahana; Morrison, Jonathan J.; Pernet, David; Renwick, Anthony; Maranian, Mel; Seal, Sheila; Ghoussaini, Maya; Hines, Sarah; Healey, Catherine S.; Hughes, Deborah; Warren-Perry, Margaret; Tapper, William; Eccles, Diana; Evans, D. Gareth; Hooning, Maartje J.; Schutte, Mieke; Ouweland, Ans van den; Houlston, Richard S.; Ross, Gillian; Langford, Cordelia; Pharoah, Paul D.P.; Stratton, Michael R.; Dunning, Alison M.; Rahman, Nazneen; Easton, Douglas F.

doi:10.1038/ng.586

Cited by 637 publications

(594 citation statements)

References 30 publications

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“…ANRIL, transcribed as a 3.8-kb lncRNA in the opposite direction from the INK4b/ARF/INK4a gene cluster, was first identified following genetic analysis of familial melanoma patients with neural tumours (19). Recently, some genomewide association studies have identified ANRIL as a risk locus for several other cancers, including breast cancer, pancreatic carcinoma, nasopharyngeal carcinoma, basal cell carcinoma, glioma and leukemia (22)(23)(24)(25)(26)(27). Inspired by these lines of evidence, we investigated ANRIL expression in SOC and analysed its clinical significance in the present study.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Qiu

Lin

Ding

et al. 2015

International Journal of Oncology

120

102

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Abstract. Recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in carcinogenesis and have suggested that genes of this class might be used as biomarkers in cancer. However, whether lncRNAs are involved in serous ovarian cancer (SOC) remains largely unknown. In the present study, we focused on lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) and investigated its expression pattern, clinical significance, and biological function in SOC. We found that ANRIL levels were elevated in SOC tissues compared with normal controls and were highly correlated with advanced FIGO stage, high histological grade, lymph node metastasis, and poor prognosis. Multivariate analysis further revealed that ANRIL is an independent prognostic factor for predicting overall survival of SOC patients. In vitro, we compared differential ANRIL levels between SOC parental cell lines (SK-OV-3, HO8910) and highly metastatic sublines (SK-OV-3.ip1, HO8910-PM). Notably, ANRIL was highly expressed in both SK-OV-3.ip1 cells and HO8910-PM cells. SiRNA-mediated ANRIL silencing in these cells impaired cell migration and invasion. Based on the metastasis-related mRNA microarray analysis and subsequent western blotting confirmation, we found that MET and MMP3 are key downstream genes of ANRIL involved in SOC cell migration/ invasion. Together, our data suggest that lncRNA ANRIL plays an important role in SOC invasion/metastasis and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Qiu

Lin

Ding

et al. 2015

International Journal of Oncology

120

102

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“…7 This association is restricted to risk of estrogenreceptor-positive (ER þ ) tumors. We previously fine-mapped this locus and found that the strongest genetic signal contained four SNPs located within a distal transcriptional enhancer (called PRE1) of CCND1 (MIM: 168461).…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Betts

Marjaneh

Al-Ejeh

et al. 2017

The American Journal of Human Genetics

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Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

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“…However, recently identified single nucleotide polymorphisms (SNP) in some genes (about 20 to date; ref. [18][19][20], which individually confer small changes in risk, may prove useful in predicting larger differences in risk when considered together.…”

Section: Introductionmentioning

confidence: 99%

Assessing Individual Breast Cancer Risk within the U.K. National Health Service Breast Screening Program: A New Paradigm for Cancer Prevention

Evans

Warwick

Astley

et al. 2012

Cancer Prevention Research

104

115

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The aim of this study is to determine breast cancer risk at mammographic screening episodes and integrate standard risk factors with mammographic density and genetic data to assess changing the screening interval based on risk and offer women at high risk preventive strategies. We report our experience of assessing breast cancer risk within the U.K. National Health Service Breast Screening Program using results from the first 10,000 women entered into the "Predicting Risk Of breast Cancer At Screening" study. Of the first 28,849 women attending for screening at fifteen sites in Manchester 10,000 (35%) consented to study entry and completed the questionnaire. The median 10-year Tyrer-Cuzick breast cancer risk was 2.65% (interquartile range, 2.10-3.45). A total of 107 women (1.07%) had 10-year risks 8% or higher (high breast cancer risk), with a further 8.20% having moderately increased risk (5%-8%). Mammographic density (percent dense area) was 60% or more in 8.3% of women. We collected saliva samples from 478 women for genetic analysis and will extend this to 18% of participants. At time of consent to the study, 95.0% of women indicated they wished to know their risk. Women with a 10-year risk of 8% or more or 5% to 8% and mammographic density of 60% or higher were invited to attend or be telephoned to receive risk counseling; 81.9% of those wishing to know their risk have received risk counseling and 85.7% of these were found to be eligible for a risk-reducing intervention. These results confirm the feasibility of determining breast cancer risk and acting on the information in the context of population-based mammographic screening. Cancer Prev Res; 5(7);

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Genome-wide association study identifies five new breast cancer susceptibility loci

Cited by 637 publications

References 30 publications

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Assessing Individual Breast Cancer Risk within the U.K. National Health Service Breast Screening Program: A New Paradigm for Cancer Prevention

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