Cancer Epidemiol Biomarkers Prev. 2020 Feb;29(2):427-433. doi: 10.1158/1055-9965.EPI-19-0374. Epub 2019 Nov 20.

Anne C Böhmer #  1   2 , Julian Hecker #  3 , Julia Schröder  4   2 , Puya Gharahkhani  5 , Andrea May  6 , Christian Gerges  7 , Mario Anders  8   9 , Jessica Becker  4   2 , Timo Hess  10 , Nicole Kreuser  11 , René Thieme  11 , Tania Noder  8 , Marino Venerito  12 , Lothar Veits  13 , Thomas Schmidt  14 , Claudia Fuchs  15 , Jakob R Izbicki  16 , Arnulf H Hölscher  15 , Arne Dietrich  11 , Yusef Moulla  11 , Orestis Lyros  11 , Hauke Lang  17 , Dietmar Lorenz  18 , Brigitte Schumacher  19 , Rupert Mayershofer  20 , Yogesh Vashist  16   21 , Katja Ott  14   22 , Michael Vieth  13 , Josef Weismüller  23 , Susanne Moebus  24 , Michael Knapp  25 , Horst Neuhaus  7 , Thomas Rösch  8 , Christian Ell  6 , Markus M Nöthen  4   2 , David C Whiteman  26 , Ian Tomlinson  27 , Janusz Jankowski  28   29 , Rebecca C Fitzgerald  30 , Claire Palles  27 , Thomas L Vaughan  31 , Ines Gockel  11 , Aaron P Thrift  32   33 , Heide Fier #  3 , Johannes Schumacher #  4   10
Affiliations

PMID: 31748258 DOI: 10.1158/1055-9965.EPI-19-0374

Abstract

Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits.

Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses.

Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 × 10-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10-02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10-03) and WHR and BE/EA risk variants (P = 2 × 10-02).

Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA.

Impact: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

©2019 American Association for Cancer Research.