Tropical Gastroenterology & Nutrition Group, Department of Internal Medicine, Lusaka, Zambia.
University of Zambia School of Medicine, Lusaka, Zambia.
Cancer Med. 2020 May;9(10):3445-3454. doi: 10.1002/cam4.3001. Epub 2020 Mar 24.
The human immunodeficiency virus (HIV) pandemic heavily affects sub-Saharan Africa. It is associated with persistently active Epstein-Barr virus (EBV) infection. To determine if this translates into increased frequency of EBV-associated gastric cancer (EBVaGC), we evaluated molecular profiles of gastric cancer (GC) in Zambia. Patients with GC or premalignant gastric lesions were enrolled in Lusaka, Zambia. We used patients without any of these lesions as a control group. Chromogenic in situ hybridization (CISH) on tumor tissue was used to identify EBVaGC. To identify the microsatellite unstable subtype, immunofluorescence staining for MutL homolog 1 (MLH1) was used. Exposure to EBV and HIV was assessed serologically. We enrolled 369 patients (median age 52 years [IQR 41-65]; 198 (54%) female). Of these, 72 (20%) had GC and 35 (9%) had gastric premalignant lesions (PL). CISH identified EBVaGC in 5/44 (11%) of those with adequate tissue, while MLH1 loss was identified in 29/45 (64%). Both GC and PL were associated with the highest titers of antibodies to Early antigen-diffuse (OR 2.5, 95% CI 1.0-6.1, P = .048 and OR 3.9, 95% CI 1.1-12.9, P = .03, respectively) at high concentrations. Human immunodeficiency virus infection was associated with a range of antibodies to EBV, but not with any cancer subtype. Despite the association of HIV with persistent EBV, the proportion of EBVaGC in Zambia is similar to populations with a low prevalence of HIV infection. The proportion of microsatellite unstable tumors may be higher than other populations.
人类免疫缺陷病毒 (HIV) 大流行严重影响撒哈拉以南非洲地区。它与持续活跃的 Epstein-Barr 病毒 (EBV) 感染有关。为了确定这是否会导致 EBV 相关胃癌 (EBVaGC) 的发病率增加，我们评估了赞比亚胃癌 (GC) 的分子谱。赞比亚卢萨卡的 GC 或癌前胃部病变患者入组。我们将没有这些病变的患者作为对照组。肿瘤组织的显色原位杂交 (CISH) 用于鉴定 EBVaGC。为了鉴定微卫星不稳定亚型，使用 MutL 同源物 1 (MLH1) 的免疫荧光染色。通过血清学评估 EBV 和 HIV 的暴露情况。我们共纳入 369 名患者（中位年龄 52 岁 [IQR 41-65]；198 名 [54%] 为女性）。其中，72 名（20%）患有 GC，35 名（9%）患有胃癌前病变 (PL)。在有足够组织的 44 名患者中，有 5 名（11%）通过 CISH 鉴定为 EBVaGC，而有 29 名（64%）通过 MLH1 缺失鉴定为 EBVaGC。GC 和 PL 均与高浓度抗体的 EBV 早期抗原弥散型的最高滴度相关（OR 2.5，95%CI 1.0-6.1，P=0.048 和 OR 3.9，95%CI 1.1-12.9，P=0.03，分别）。人类免疫缺陷病毒感染与 EBV 的一系列抗体相关，但与任何癌症亚型均无关。尽管 HIV 与持续的 EBV 有关，但赞比亚的 EBVaGC 比例与 HIV 感染率低的人群相似。微卫星不稳定肿瘤的比例可能高于其他人群。
