Search

Your search keyword '"Katie Ashton"' showing total 11 results
Start Over Author "Katie Ashton"
11 results on '"Katie Ashton"'

1. Biallelic SLC13A1 loss-of-function variants result in impaired sulfate transport and skeletal phenotypes, including short stature, scoliosis, and skeletal dysplasia

Author

Christina G. Tise, Katie Ashton, Lachlan de Hayr, Kun-Di Lee, Omkar L. Patkar, Emma Krzesinski, Jennifer A. Bassetti, Erin M. Carter, Cathleen Raggio, Andreas Zankl, Anas M. Khanshour, Kristhen N. Atala, Jonathan J. Rios, Carol A. Wise, Ying Zhu, Futao Zhang, Tony Roscioli, Michael Buckley, Robert J. Harvey, and Paul A. Dawson

Subjects
Hyposulfatemia, Scoliosis, Short stature, Skeletal dysplasia, Sulfate transporter, Genetics, QH426-470, Medicine
Abstract

Purpose: Sulfate is vital for many physiological processes, including the structural and functional maintenance of macromolecules and formation of sulfur-containing compounds essential for cartilage and bone development. SLC13A1 is a sodium-sulfate cotransporter primarily expressed in the kidney, where it mediates sulfate reabsorption and maintenance of circulating sulfate levels. In this study, we characterized the clinical, biochemical, and functional impact of biallelic SLC13A1 nonsense and/or missense variants in individuals presenting with a skeletal phenotype. Methods: Probands were identified by exome or genome sequencing and GeneMatcher. Sulfate levels were quantified using ion chromatography. SLC13A1 missense variants p.(Arg237Cys), p.(Gly448Asp), p.(Leu516Pro), and p.(Tyr582His) were characterized using bioinformatics, molecular modeling, and [35S]-sulfate uptake assays in Madin-Darby canine kidney cells. Results: All probands presented with concern for short stature and were found to have scoliosis and/or skeletal dysplasia. A reduction in plasma sulfate level and/or increase in urinary sulfate excretion was detected in 2 of 2 probands evaluated. Functional studies were consistent with SLC13A1 variants resulting in the complete loss of sulfate transport activity. Conclusion: Biallelic loss-of-function variants in SLC13A1 are a novel cause of skeletal phenotypes in humans with a measurable biomarker. Sulfate measurements should be considered in the clinical interpretation of variants identified in SLC13A1.

Published
2025
Full Text
View/download PDF

2. Identification of nine new susceptibility loci for endometrial cancer

Author

Tracy A. O’Mara, Dylan M. Glubb, Frederic Amant, Daniela Annibali, Katie Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H. T. Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao-Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M. J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong-Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D. P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, and Deborah J. Thompson

Subjects
Science
Abstract

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Published
2018
Full Text
View/download PDF

3. Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses

Author

Jodie N. Painter, Tracy A. O'Mara, Andrew P. Morris, Timothy H. T. Cheng, Maggie Gorman, Lynn Martin, Shirley Hodson, Angela Jones, Nicholas G. Martin, Scott Gordon, Anjali K. Henders, John Attia, Mark McEvoy, Elizabeth G. Holliday, Rodney J. Scott, Penelope M. Webb, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Matthias Rübner, Per Hall, Kamila Czene, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo Runnebaum, Diether Lambrechts, Frederic Amant, Daniela Annibali, Jeroen Depreeuw, Adriaan Vanderstichele, Ellen L. Goode, Julie M. Cunningham, Sean C. Dowdy, Stacey J. Winham, Jone Trovik, Erling Hoivik, Henrica M. J. Werner, Camilla Krakstad, Katie Ashton, Geoffrey Otton, Tony Proietto, Emma Tham, Miriam Mints, Shahana Ahmed, Catherine S. Healey, Mitul Shah, Paul D. P. Pharoah, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P. Tyrer, John L. Hopper, Julian Peto, Anthony J. Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang‐Claude, Fergus J. Couch, Graham G. Giles, Vessela N. Kristensen, Angela Cox, Krina T. Zondervan, Dale R. Nyholt, Stuart MacGregor, Grant W. Montgomery, Ian Tomlinson, Douglas F. Easton, Deborah J. Thompson, and Amanda B. Spurdle

Subjects
Cross‐disease analysis, endometrial cancer, endometriosis, genome‐wide association study, genetic correlation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

Published
2018
Full Text
View/download PDF

4. Supplementary Figure 1 from Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Author

Xiao-Ou Shu, Amanda B. Spurdle, Qiuyin Cai, Yu-Tang Gao, Douglas Easton, Alison Dunning, Wei Lu, Hui Cai, Anthony Proietto, Alexander Hein, Mari K. Halle, Rayna K. Matsuno, An Coosemans, Louise Brinton, Maggie Gorman, Ben Zhang, Jiajun Shi, Geoffrey Otton, Arif B. Ekici, Camilla Krakstad, Pamela J. Thompson, Matthias Dürst, Dilyara Kaidarova, Lieve Coenegrachts, Jolanta Lissowska, Lingeng Lu, Kimberly Howarth, Ping-Ping Bao, Bu-Tian Ji, Katie Ashton, Matthias W. Beckmann, Jone Trovik, Galina Lurie, Anita Schwake, Nurzhan Turmanov, Frederic Amant, Hannah P. Yang, Harvey Risch, Shirley Hodgson, Catherine S. Healey, Tracy O'Mara, Ying Zheng, Ryan Delahanty, Rodney J. Scott, Peter A. Fasching, Helga B. Salvesen, Marc T. Goodman, Natalia Dubrowinskaja, Thilo Dörk, Diether Lambrechts, Nicolas Wentzensen, Herbert Yu, Ian Tomlinson, Deborah Thompson, Felicity Lose, Yong-Bing Xiang, Wei Zheng, and Jirong Long

Abstract

PDF file, 53KB.

Published
2023
Full Text
View/download PDF

5. Data from Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Author

Xiao-Ou Shu, Amanda B. Spurdle, Qiuyin Cai, Yu-Tang Gao, Douglas Easton, Alison Dunning, Wei Lu, Hui Cai, Anthony Proietto, Alexander Hein, Mari K. Halle, Rayna K. Matsuno, An Coosemans, Louise Brinton, Maggie Gorman, Ben Zhang, Jiajun Shi, Geoffrey Otton, Arif B. Ekici, Camilla Krakstad, Pamela J. Thompson, Matthias Dürst, Dilyara Kaidarova, Lieve Coenegrachts, Jolanta Lissowska, Lingeng Lu, Kimberly Howarth, Ping-Ping Bao, Bu-Tian Ji, Katie Ashton, Matthias W. Beckmann, Jone Trovik, Galina Lurie, Anita Schwake, Nurzhan Turmanov, Frederic Amant, Hannah P. Yang, Harvey Risch, Shirley Hodgson, Catherine S. Healey, Tracy O'Mara, Ying Zheng, Ryan Delahanty, Rodney J. Scott, Peter A. Fasching, Helga B. Salvesen, Marc T. Goodman, Natalia Dubrowinskaja, Thilo Dörk, Diether Lambrechts, Nicolas Wentzensen, Herbert Yu, Ian Tomlinson, Deborah Thompson, Felicity Lose, Yong-Bing Xiang, Wei Zheng, and Jirong Long

Abstract

Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer.Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb).Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5).Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus.Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980–7. ©2012 AACR.

Published
2023
Full Text
View/download PDF

6. Supplementary Tables 1 - 4 from Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Author

Xiao-Ou Shu, Amanda B. Spurdle, Qiuyin Cai, Yu-Tang Gao, Douglas Easton, Alison Dunning, Wei Lu, Hui Cai, Anthony Proietto, Alexander Hein, Mari K. Halle, Rayna K. Matsuno, An Coosemans, Louise Brinton, Maggie Gorman, Ben Zhang, Jiajun Shi, Geoffrey Otton, Arif B. Ekici, Camilla Krakstad, Pamela J. Thompson, Matthias Dürst, Dilyara Kaidarova, Lieve Coenegrachts, Jolanta Lissowska, Lingeng Lu, Kimberly Howarth, Ping-Ping Bao, Bu-Tian Ji, Katie Ashton, Matthias W. Beckmann, Jone Trovik, Galina Lurie, Anita Schwake, Nurzhan Turmanov, Frederic Amant, Hannah P. Yang, Harvey Risch, Shirley Hodgson, Catherine S. Healey, Tracy O'Mara, Ying Zheng, Ryan Delahanty, Rodney J. Scott, Peter A. Fasching, Helga B. Salvesen, Marc T. Goodman, Natalia Dubrowinskaja, Thilo Dörk, Diether Lambrechts, Nicolas Wentzensen, Herbert Yu, Ian Tomlinson, Deborah Thompson, Felicity Lose, Yong-Bing Xiang, Wei Zheng, and Jirong Long

Abstract

PDF file, 112KB.

Published
2023
Full Text
View/download PDF

7. Supplementary Figure 2 from Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Author

Xiao-Ou Shu, Amanda B. Spurdle, Qiuyin Cai, Yu-Tang Gao, Douglas Easton, Alison Dunning, Wei Lu, Hui Cai, Anthony Proietto, Alexander Hein, Mari K. Halle, Rayna K. Matsuno, An Coosemans, Louise Brinton, Maggie Gorman, Ben Zhang, Jiajun Shi, Geoffrey Otton, Arif B. Ekici, Camilla Krakstad, Pamela J. Thompson, Matthias Dürst, Dilyara Kaidarova, Lieve Coenegrachts, Jolanta Lissowska, Lingeng Lu, Kimberly Howarth, Ping-Ping Bao, Bu-Tian Ji, Katie Ashton, Matthias W. Beckmann, Jone Trovik, Galina Lurie, Anita Schwake, Nurzhan Turmanov, Frederic Amant, Hannah P. Yang, Harvey Risch, Shirley Hodgson, Catherine S. Healey, Tracy O'Mara, Ying Zheng, Ryan Delahanty, Rodney J. Scott, Peter A. Fasching, Helga B. Salvesen, Marc T. Goodman, Natalia Dubrowinskaja, Thilo Dörk, Diether Lambrechts, Nicolas Wentzensen, Herbert Yu, Ian Tomlinson, Deborah Thompson, Felicity Lose, Yong-Bing Xiang, Wei Zheng, and Jirong Long

Abstract

PDF file, 45KB.

Published
2023
Full Text
View/download PDF

8. Supplementary Methods from Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Author

Xiao-Ou Shu, Amanda B. Spurdle, Qiuyin Cai, Yu-Tang Gao, Douglas Easton, Alison Dunning, Wei Lu, Hui Cai, Anthony Proietto, Alexander Hein, Mari K. Halle, Rayna K. Matsuno, An Coosemans, Louise Brinton, Maggie Gorman, Ben Zhang, Jiajun Shi, Geoffrey Otton, Arif B. Ekici, Camilla Krakstad, Pamela J. Thompson, Matthias Dürst, Dilyara Kaidarova, Lieve Coenegrachts, Jolanta Lissowska, Lingeng Lu, Kimberly Howarth, Ping-Ping Bao, Bu-Tian Ji, Katie Ashton, Matthias W. Beckmann, Jone Trovik, Galina Lurie, Anita Schwake, Nurzhan Turmanov, Frederic Amant, Hannah P. Yang, Harvey Risch, Shirley Hodgson, Catherine S. Healey, Tracy O'Mara, Ying Zheng, Ryan Delahanty, Rodney J. Scott, Peter A. Fasching, Helga B. Salvesen, Marc T. Goodman, Natalia Dubrowinskaja, Thilo Dörk, Diether Lambrechts, Nicolas Wentzensen, Herbert Yu, Ian Tomlinson, Deborah Thompson, Felicity Lose, Yong-Bing Xiang, Wei Zheng, and Jirong Long

Abstract

PDF file, 123KB, Detailed Description of the Case and Control Sample Sets.

Published
2023
Full Text
View/download PDF

10. Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

Author

Emma Tudini, James Andrews, David M. Lawrence, Sarah L. King-Smith, Naomi Baker, Leanne Baxter, John Beilby, Bruce Bennetts, Victoria Beshay, Michael Black, Tiffany F. Boughtwood, Kristian Brion, Pak Leng Cheong, Michael Christie, John Christodoulou, Belinda Chong, Kathy Cox, Mark R. Davis, Lucas Dejong, Marcel E. Dinger, Kenneth D. Doig, Evelyn Douglas, Andrew Dubowsky, Melissa Ellul, Andrew Fellowes, Katrina Fisk, Cristina Fortuno, Kathryn Friend, Renee L. Gallagher, Song Gao, Emma Hackett, Johanna Hadler, Michael Hipwell, Gladys Ho, Georgina Hollway, Amanda J. Hooper, Karin S. Kassahn, Rahul Krishnaraj, Chiyan Lau, Huong Le, Huei San Leong, Ben Lundie, Sebastian Lunke, Anthony Marty, Mary McPhillips, Lan T. Nguyen, Katia Nones, Kristen Palmer, John V. Pearson, Michael C.J. Quinn, Lesley H. Rawlings, Simon Sadedin, Louisa Sanchez, Andreas W. Schreiber, Emanouil Sigalas, Aygul Simsek, Julien Soubrier, Zornitza Stark, Bryony A. Thompson, James U, Cassandra G. Vakulin, Amanda V. Wells, Cheryl A. Wise, Rick Woods, Andrew Ziolkowski, Marie-Jo Brion, Hamish S. Scott, Natalie P. Thorne, Amanda B. Spurdle, Lauren Akesson, Richard Allcock, Katie Ashton, Damon A. Bell, Anna Brown, Michael Buckley, John R. Burnett, Linda Burrows, Alicia Byrne, Eva Chan, Corrina Cliffe, Roderick Clifton-Bligh, Susan Dooley, Miriam Fanjul Fernandez, Elizabeth Farnsworth, Thuong Ha, Denae Henry, Duncan Holds, Katherine Holman, Matilda Jackson, Sinlay Kang, Catherine Luxford, Sam McManus, Rachael Mehrtens, Cliff Meldrum, David Mossman, Sarah-Jane Pantaleo, Dean Phelan, Electra Pontikinas, Anja Ravine, Tony Roscioli, Rodney Scott, Keryn Simons, Oliver Vanwageningen, Tudini, Emma, Andrews, James, Lawrence, David M., King-Smith, Sarah L., Schreiber, Andreas W, James, U, and Shariant Consortium

Subjects
genomic variant, variant interpretations, Databases, Genetic, Technology Review, Genetics, Australia, Humans, Genetic Variation, Genetic Testing, Laboratories, Genetics (clinical), Australian laboratories
Abstract

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

Published
2022

11. Association of a Common AKAP9 Variant With Breast Cancer Risk: A Collaborative Analysis

Author

Christina Justenhoven, Jonathan Beesley, Kari Hemminki, Paul P.D. Pharoah, Douglas F. Easton, Miriam Wiestler, Georgia Chenevix-Trench, Jenny Chang-Claude, Alison M. Dunning, Isabel dos Santos Silva, Silke Kropp, Hiltrud Brauch, Richard S. Houlston, Alfons Meindl, Xiaoqing Chen, Katie Ashton, Ramona Salazar, Yon-Dschun Ko, Dieter Flesch-Janys, Emily L. Webb, Bernd Frank, Barbara Wappenschmidt, Christian Sutter, Rita K. Schmutzler, Julian Peto, Barbara Burwinkel, Karen A. Pooley, Amanda B. Spurdle, Ute Hamann, Thomas Brüning, Marion Kiechle, Elke Mutschelknauss, Claus R. Bartram, John L. Hopper, Nichola Johnson, Peter Bugert, Tracy Slanger, and Olivia Fletcher

Subjects
Adult, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Linkage disequilibrium, A Kinase Anchor Proteins, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Risk Assessment, Linkage Disequilibrium, White People, Methionine, Breast cancer, Risk Factors, Germany, Internal medicine, Genotype, Humans, Medicine, Genetic Predisposition to Disease, Isoleucine, Alleles, Aged, business.industry, Australia, Case-control study, Cancer, Odds ratio, Middle Aged, medicine.disease, Europe, Cytoskeletal Proteins, Research Design, Case-Control Studies, Female, Breast disease, business
Abstract

Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous single-nucleotide polymorphisms that were predicted to be deleterious and found two (M463I, 1389G>T and N2792S, 8375A>G) to be associated with an allele dose-dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M463I, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M463I with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001).

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results