TY - JOUR
T1 - Polymorphisms in genes of relevance for oestrogen and oxytocin pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma
T2 - A pooled analysis from the BEACON consortium
AU - Lagergren, Katarina
AU - Ek, Weronica E.
AU - Levine, David
AU - Chow, Wong Ho
AU - Bernstein, Leslie
AU - Casson, Alan G.
AU - Risch, Harvey A.
AU - Shaheen, Nicholas J.
AU - Bird, Nigel C.
AU - Reid, Brian J.
AU - Corley, Douglas A.
AU - Hardie, Laura J.
AU - Wu, Anna H.
AU - Fitzgerald, Rebecca C.
AU - Pharoah, Paul
AU - Caldas, Carlos
AU - Romero, Yvonne
AU - Vaughan, Thomas L.
AU - Macgregor, Stuart
AU - Whiteman, David
AU - Westberg, Lars
AU - Nyren, Olof
AU - Lagergren, Jesper
PY - 2015/9/25
Y1 - 2015/9/25
N2 - Background: 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. Methods: 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). Results: 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. Conclusion: 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.
AB - Background: 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. Methods: 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). Results: 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. Conclusion: 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.
UR - https://www.scopus.com/pages/publications/84947795687
U2 - 10.1371/journal.pone.0138738
DO - 10.1371/journal.pone.0138738
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C2 - 26406593
AN - SCOPUS:84947795687
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0138738
ER -