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Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation

Overview of attention for article published in American Journal of Human Genetics, October 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (72nd percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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11 tweeters
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1 Facebook page

Citations

dimensions_citation
19 Dimensions

Readers on

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48 Mendeley
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2 CiteULike
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Title
Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation
Published in
American Journal of Human Genetics, October 2016
DOI 10.1016/j.ajhg.2016.07.017
Pubmed ID
Authors

Maya Ghoussaini, Juliet D. French, Kyriaki Michailidou, Silje Nord, Jonathan Beesley, Sander Canisus, Kristine M. Hillman, Susanne Kaufmann, Haran Sivakumaran, Mahdi Moradi Marjaneh, Jason S. Lee, Joe Dennis, Manjeet K. Bolla, Qin Wang, Ed Dicks, Roger L. Milne, John L. Hopper, Melissa C. Southey, Marjanka K. Schmidt, Annegien Broeks, Kenneth Muir, Artitaya Lophatananon, Peter A. Fasching, Matthias W. Beckmann, Olivia Fletcher, Nichola Johnson, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérèse Truong, Stig E. Bojesen, Henrik Flyger, Javier Benitez, Anna González-Neira, M. Rosario Alonso, Guillermo Pita, Susan L. Neuhausen, Hoda Anton-Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Daniel C. Tessier, Daniel Vincent, Heli Nevanlinna, Sofia Khan, Keitaro Matsuo, Hidemi Ito, Thilo Dörk, Natalia V. Bogdanova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Anna H. Wu, David Van Den Berg, Diether Lambrechts, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Monica Barile, Fergus J. Couch, Emily Hallberg, Graham G. Giles, Christopher A. Haiman, Loic Le Marchand, Mark S. Goldberg, Soo H. Teo, Cheng Har Yip, Anne-Lise Borresen-Dale, Wei Zheng, Qiuyin Cai, Robert Winqvist, Katri Pylkäs, Irene L. Andrulis, Peter Devilee, Rob A.E.M. Tollenaar, Montserrat García-Closas, Jonine Figueroa, Per Hall, Kamila Czene, Judith S. Brand, Hatef Darabi, Mikael Eriksson, Maartje J. Hooning, Linetta B. Koppert, Jingmei Li, Xiao-Ou Shu, Ying Zheng, Angela Cox, Simon S. Cross, Mitul Shah, Valerie Rhenius, Ji-Yeob Choi, Daehee Kang, Mikael Hartman, Kee Seng Chia, Maria Kabisch, Diana Torres, Craig Luccarini, Don M. Conroy, Anna Jakubowska, Jan Lubinski, Suleeporn Sangrajrang, Paul Brennan, Curtis Olswold, Susan Slager, Chen-Yang Shen, Ming-Feng Hou, Anthony Swerdlow, Minouk J. Schoemaker, Jacques Simard, Paul D.P. Pharoah, Vessela Kristensen, Georgia Chenevix-Trench, Douglas F. Easton, Alison M. Dunning, Stacey L. Edwards

Abstract

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10(-30)). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER(-)) breast cancer (lead SNP rs6864776: per-a allele OR ER(-) = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10(-12)), and a single signal 3 SNP (rs200229088: per-t allele OR ER(+) = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10(-05)). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

Twitter Demographics

The data shown below were collected from the profiles of 11 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Finland 1 2%
Norway 1 2%
Unknown 46 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 31%
Student > Ph. D. Student 8 17%
Unspecified 7 15%
Student > Bachelor 6 13%
Professor 4 8%
Other 8 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 25%
Unspecified 10 21%
Medicine and Dentistry 10 21%
Agricultural and Biological Sciences 9 19%
Social Sciences 2 4%
Other 5 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 May 2017.
All research outputs
#2,936,516
of 12,376,939 outputs
Outputs from American Journal of Human Genetics
#1,923
of 4,403 outputs
Outputs of similar age
#71,953
of 265,324 outputs
Outputs of similar age from American Journal of Human Genetics
#48
of 70 outputs
Altmetric has tracked 12,376,939 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,403 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.6. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 265,324 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.