TY - JOUR
T1 - Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus
AU - Dong, Jing
AU - Levine, David M.
AU - Buas, Matthew F.
AU - Zhang, Rui
AU - Onstad, Lynn
AU - Fitzgerald, Rebecca C.
AU - Corley, Douglas A.
AU - Shaheen, Nicholas J.
AU - Lagergren, Jesper
AU - Hardie, Laura J.
AU - Reid, Brian J.
AU - Iyer, Prasad G.
AU - Risch, Harvey A.
AU - Caldas, Carlos
AU - Caldas, Isabel
AU - Pharoah, Paul D.
AU - Liu, Geoffrey
AU - Gammon, Marilie D.
AU - Chow, Wong Ho
AU - Bernstein, Leslie
AU - Bird, Nigel C.
AU - Ye, Weimin
AU - Wu, Anna H.
AU - Anderson, Lesley A.
AU - MacGregor, Stuart
AU - Whiteman, David C.
AU - Vaughan, Thomas L.
AU - Thrift, Aaron P.
AU - Stomach and Oesophageal Cancer Study (SOCS) Consortium
PY - 2018/10
Y1 - 2018/10
N2 - Background & Aims: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. Methods: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case–control logistic regression to test for gene-environment interactions. Results: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10-7). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03–34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), respectively. Conclusion: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.
AB - Background & Aims: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. Methods: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case–control logistic regression to test for gene-environment interactions. Results: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10-7). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03–34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), respectively. Conclusion: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.
KW - Esophageal Neoplasm
KW - Esophagus
KW - Genetic Variants
KW - Risk Factors
UR - http://www.scopus.com/inward/record.url?scp=85050937462&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2018.03.007
DO - 10.1016/j.cgh.2018.03.007
M3 - Article
C2 - 29551738
AN - SCOPUS:85050937462
VL - 16
SP - 1598-1606.e4
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 10
ER -
