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
Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala, Sweden.
PLoS One. 2015 Sep 25;10(9):e0138738. doi: 10.1371/journal.pone.0138738. eCollection 2015.
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.
背景：食管腺癌（OAC）和巴雷特食管（BO）中男性占比过高的情况一直令人困惑。激素影响，如雌激素或催产素，可能是原因之一。 方法：这项遗传流行病学研究汇总了来自三大洲（澳大利亚、欧洲和北美）的14项研究。使用基于基因的方法，即通用基因关联研究（VEGAS），分析了雌激素途径的3个关键基因（受体α（ESR1）、受体β（ESR2）和芳香化酶（CYP19A1））以及催产素途径的3个关键基因（催产素受体（OXTR）、催产素蛋白（OXT）和环ADP核糖水解酶糖蛋白（CD38））中的多态性。 结果：在1508例OAC患者、2383例BO患者和2170例对照中，ESR1基因内的遗传变异与男性的BO相关（p = 0.0058），且与男性OAC和BO合并风险增加相关（p = 0.0023）。OXTR基因内的遗传变异与男女合并的BO风险增加相关（p = 0.0035），在男性中也相关（p = 0.0012）。我们在一个更小的数据集中对这些提示性发现进行了随访，但未发现重复结果。所研究的其他4个基因与OAC、BO的风险之间，无论单独还是合并，在男女合并或仅男性中均无显著关联。 结论：雌激素受体α和催产素受体的遗传变异可能与BO或OAC风险增加相关，但需要在其他大样本中进行重复验证。
Eur J Cancer. 2017-4
Br J Cancer. 2015-4-14
Aliment Pharmacol Ther. 2014-4-16
Int J Mol Sci. 2023-2-15
BMC Bioinformatics. 2019-12-30
Gastroenterology. 2017-9
Biomed Res Int. 2016
J Natl Cancer Inst. 2013-10-29
CA Cancer J Clin. 2013
Dis Esophagus. 2012-11-16
Biol Sex Differ. 2012-7-30
Am J Gastroenterol. 2012-6
Zotero 插件