Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux

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Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux

Ek, Weronica E (author)

Levine, D. M. (author)

D'Amato, M. (author): Karolinska Institutet

Pedersen, N. L. (author): Karolinska Institutet

Magnusson, P. K. E. (author): Karolinska Institutet

Bresso, F. (author): Karolinska Institutet

Onstad, L. E. (author)

Schmidt, P. T. (author): Karolinska Institutet

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

Nordenstedt, H. (author): Karolinska Institutet

Romero, Y. (author)

Chow, W. H. (author)

Murray, L. J. (author)

Gammon, M. D. (author)

Liu, G. (author)

Bernstein, L. (author)

Casson, A. G. (author)

Risch, H. A. (author)

Shaheen, N. J. (author)

Bird, N. C. (author)

Reid, B. J. (author)

Corley, D. A. (author)

Hardie, L. J. (author)

Ye, W. (author): Karolinska Institutet

Wu, A. H. (author)

Zucchelli, M. (author): Karolinska Institutet

Spector, T. D. (author)

Hysi, P. (author)

Vaughan, T. L. (author)

Whiteman, D. C. (author)

MacGregor, S. (author)

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(creator_code:org_t)

2013-10-29
2013
English.
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718

Related links:: https://academic.oup...; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; https://urn.kb.se/re...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Gastroenterology ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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By the university: University of Gothenburg; Uppsala University; Karolinska Institutet

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