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Germline genetic co...
Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
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Ek, Weronica E (author)
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Levine, D. M. (author)
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- D'Amato, M. (author)
- Karolinska Institutet
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- Pedersen, N. L. (author)
- Karolinska Institutet
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- Magnusson, P. K. E. (author)
- Karolinska Institutet
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- Bresso, F. (author)
- Karolinska Institutet
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Onstad, L. E. (author)
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- Schmidt, P. T. (author)
- Karolinska Institutet
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- Törnblom, Hans, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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- Nordenstedt, H. (author)
- Karolinska Institutet
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Romero, Y. (author)
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Chow, W. H. (author)
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Murray, L. J. (author)
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Gammon, M. D. (author)
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Liu, G. (author)
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Bernstein, L. (author)
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Casson, A. G. (author)
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Risch, H. A. (author)
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Shaheen, N. J. (author)
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Bird, N. C. (author)
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Reid, B. J. (author)
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Corley, D. A. (author)
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Hardie, L. J. (author)
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- Ye, W. (author)
- Karolinska Institutet
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Wu, A. H. (author)
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- Zucchelli, M. (author)
- Karolinska Institutet
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Spector, T. D. (author)
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Hysi, P. (author)
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Vaughan, T. L. (author)
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Whiteman, D. C. (author)
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MacGregor, S. (author)
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(creator_code:org_t)
- 2013-10-29
- 2013
- English.
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- article
- Barrett esophagus
- body mass
- case control study
- controlled study
- esophageal adenocarcinoma
- female
- gastroesophageal reflux
- genetic association
- genetic correlation
- genetic risk
- genetic trait
- genetic variability
- heritability
- human
- major clinical study
- male
- molecular phylogeny
- prediction
- priority journal
- sex difference
- single nucleotide polymorphism
- smoking
- Sweden
- United Kingdom
- X chromosome
- Adenocarcinoma
- Adult
- Aged
- Case-Control Studies
- Chromosome Disorders
- Esophageal Neoplasms
- Genome-Wide Association Study
- Germ-Line Mutation
- Humans
- Middle Aged
- Polymorphism
- Single Nucleotide
- Predictive Value of Tests
- Prevalence
- Risk Assessment
- Risk Factors
- Sex Factors
- Software
- Twin Studies as Topic
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Ek, Weronica E
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Levine, D. M.
-
D'Amato, M.
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Pedersen, N. L.
-
Magnusson, P. K. ...
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Bresso, F.
-
show more...
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Onstad, L. E.
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Schmidt, P. T.
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Törnblom, Hans, ...
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Nordenstedt, H.
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Romero, Y.
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Chow, W. H.
-
Murray, L. J.
-
Gammon, M. D.
-
Liu, G.
-
Bernstein, L.
-
Casson, A. G.
-
Risch, H. A.
-
Shaheen, N. J.
-
Bird, N. C.
-
Reid, B. J.
-
Corley, D. A.
-
Hardie, L. J.
-
Ye, W.
-
Wu, A. H.
-
Zucchelli, M.
-
Spector, T. D.
-
Hysi, P.
-
Vaughan, T. L.
-
Whiteman, D. C.
-
MacGregor, S.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Journal of the N ...
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet