Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium

• Published in: PloS one Vol. 10; no. 9; p. e0138738
• Main Authors: Lagergren, Katarina, Ek, Weronica E, Levine, David, Chow, Wong-Ho, Bernstein, Leslie, Casson, Alan G, Risch, Harvey A, Shaheen, Nicholas J, Bird, Nigel C, Reid, Brian J, Corley, Douglas A, Hardie, Laura J, Wu, Anna H, Fitzgerald, Rebecca C, Pharoah, Paul, Caldas, Carlos, Romero, Yvonne, Vaughan, Thomas L, MacGregor, Stuart, Whiteman, David, Westberg, Lars, Nyren, Olof, Lagergren, Jesper
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2015; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - epidemiology; Adenocarcinoma - genetics; Adenosine diphosphate; ADP-ribosyl Cyclase 1 - genetics; Aromatase; Aromatase - genetics; Barrett Esophagus - epidemiology; Barrett Esophagus - genetics; Barrett's esophagus; Breast cancer; Breastfeeding & lactation; cancer; carcinoma; CD38 antigen; Cell growth; Consortia; Continents; Cyclic ADP-ribose; Epidemiology; Esophageal cancer; Esophageal Neoplasms - epidemiology; Esophageal Neoplasms - genetics; Esophagus; esr1 gene; ESR1 protein; Estrogen Receptor alpha - genetics; Estrogen Receptor beta - genetics; Female; Females; Gastroenterology; gastroesophageal-reflux; Gastrointestinal surgery; Genes; Genetic Association Studies - methods; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetics; genome-wide association; Genomes; Glycoproteins; Health care; Hepatology; Humans; Hydrolase; Hypotheses; Male; Males; Medical research; Medicin och hälsovetenskap; Membrane Glycoproteins - genetics; netics; Neurosciences; Neurovetenskaper; Oxytocin; Oxytocin - genetics; p1391; Pathology; Patients; Polymorphism, Single Nucleotide; postmenopausal women; Preventive medicine; proliferation; Public health; receptor gene; Receptors, Oxytocin - genetics; Replication; Ribose; Risk; Science & Technology - Other Topics; Sex Factors; social-behavior; Studies; v153b; variability; Womens health; Sweden; California; Queensland Australia; Australia; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138738

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.