uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux
Show others and affiliations
2013 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 105, no 22, 1711-8 p.Article in journal (Refereed) Published
Abstract [en]

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, h(2)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 two-sided, 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 (h(2)g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10(-9)) and for EA (h(2)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.

Place, publisher, year, edition, pages
2013. Vol. 105, no 22, 1711-8 p.
National Category
Medical Genetics
URN: urn:nbn:se:uu:diva-231921DOI: 10.1093/jnci/djt303PubMedID: 24168968OAI: oai:DiVA.org:uu-231921DiVA: diva2:745824
Available from: 2014-09-11 Created: 2014-09-11 Last updated: 2014-09-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ek, Weronica E
In the same journal
Journal of the National Cancer Institute
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 175 hits
ReferencesLink to record
Permanent link

Direct link