Gastro-oesophageal cancers were ranked as the second cause of death from cancer worldwide despite a steady decrease in incidence for squamous cell carcinoma (SCC) of the oesophagus and distal gastric cancers. Adenocarcinoma of the oesophagus (OAC) is the tumour whose incidence has seen the highest increase in the past 30 years. Most of these cancers are strongly associated with environmental and life style risk factors such as smoking and alcohol for SCC, gastro-oesophageal reflux for OAC and Helicobacter pylori for distal gastric cancer. It may therefore be unsurprising that SCC is associated with polymorphisms in ALDH2 and ADH1B1, enzyme involved in alcohol metabolism, and with CYP1A1, involved in xenobiotics detoxification. OAC, whose incidence in absolute terms remains low, has been much less studied and at best the associations identified with risk are weak. Diffuse type gastric cancers while relatively uncommon have a strong genetic association with mutation of the CDH1 gene and prostate specific cancer antigen (PSCA) was demonstrated in a GWAS to be associated with an increased risk of diffuse gastric cancer but not intestinal type gastric cancer. This family of cancer is more associated with polymorphisms at the IL-1beta, IL-1RN loci and MHTFR loci. Specific strains of H pylori containing the virulence factors VacA s1, VacA m1 and cag A together with polymorphism at the IL-1beta and IL-1RN loci have up to a 87-fold increase in risk for developing intestinal type gastric cancer. While progress has been made to identify genetic variants associated with upper-gastrointestinal cancers, the relative small prevalence for some subtypes underlies the need for consortia, especially in view of the large variations in the prevalence of polymorphisms between different populations.

中文翻译：

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胃食管癌的遗传易感性。

尽管食管鳞状细胞癌 (SCC) 和远端胃癌的发病率稳步下降，但胃食管癌仍被列为全球癌症死亡的第二大原因。食管腺癌 (OAC) 是过去 30 年来发病率增长最快的肿瘤。大多数这些癌症与环境和生活方式风险因素密切相关，例如 SCC 的吸烟和酒精、OAC 的胃食管反流和远端胃癌的幽门螺杆菌。因此，SCC 与参与酒精代谢的酶 ALDH2 和 ADH1B1 的多态性以及参与异生素解毒的 CYP1A1 的多态性相关可能不足为奇。OAC，其绝对发生率仍然很低，研究较少，而且与风险的关联充其量是微弱的。弥漫型胃癌虽然相对少见，但与 CDH1 基因的突变有很强的遗传关联，GWAS 证明前列腺特异性癌抗原 (PSCA) 与弥漫型胃癌的风险增加有关，但与肠型胃癌的风险无关。这个癌症家族更多地与 IL-1beta、IL-1RN 基因座和 MHTFR 基因座的多态性相关。含有毒力因子 VacA s1、VacA m1 和 cag A 以及 IL-1beta 和 IL-1RN 基因座多态性的特定幽门螺杆菌菌株，其患肠型胃癌的风险增加了 87 倍。虽然在鉴定与上消化道癌症相关的遗传变异方面取得了进展，