Department of Gastroenterology, PGIMER, Chandigarh, India.
Department of Radiology, PGIMER, Chandigarh, India.
Int J Cancer. 2025 Jan 15;156(2):322-330. doi: 10.1002/ijc.35171. Epub 2024 Sep 6.
Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.
胆囊癌(GBC)在某些地理区域的社会经济贫困人群中很常见。黄曲霉毒素是一种遗传毒性肝致癌物,已被认为在肝细胞癌的发病机制中起作用。然而,黄曲霉毒素在 GBC 发病机制中的作用在很大程度上尚不清楚。我们确定了 GBC 患者血清 AFB1-Lys 白蛋白加合物(AAA)水平作为黄曲霉毒素暴露的标志物,并将其与无 GBC 患者进行了比较。评估了 AAA 水平与细胞遗传学(TP53 突变和 HER2/neu 扩增)和肿瘤影像学特征的关系。我们纳入了 GBC 病例(n=51)和非 GBC 对照组(n=100)。GBC 组(n=51)的平均血清 AAA 水平高于无 GBC 组(n=100)(26.1±12.2 与 13.1±11.9ng/ml;p<0.001)。与表达不确定或阴性的相比,HER2/neu 表达与更高的 AAA 水平相关(43.9±3 与 28.6±10 与 19.3±7ng/ml;p<0.001)。年龄较大(>50 岁)(比值比[OR] = 3.2 [95%置信区间:1.3-8.2];p=0.013)、幽门螺杆菌血清学阳性(OR = 5.1 [95%置信区间:1.4-17.8];p=0.012)、GS 存在(OR = 5 [95%置信区间:1.5-16.9];p=0.009)和可检测的 AAA 水平(OR = 6.8 [95%置信区间:1.3-35.7];p=0.024)是所有研究对象中 GBC 存在的独立危险因素。在携带 GS 的患者中,年龄较大(>50 岁)(OR = 4.5 [95%置信区间:1.3-14.9];p=0.015)、女性(OR = 3.8 [95%置信区间:1.2-12.5];p=0.027)、多发性 GS(OR = 21.9 [95%置信区间:4.8-100.4];p<0.001)和高血清 AAA 水平(OR = 5.3 [95%置信区间:1.6-17.3];p=0.006)是 GBC 存在的独立危险因素。年龄较大(>50 岁)(OR = 2.6 [95%置信区间:1.3-5.2];p=0.010)和经常食用花生(OR = 2.3 [95%置信区间:1.1-4.9];p=0.030)是高血清 AAA 水平的独立危险因素。本研究提示通过减少饮食中黄曲霉毒素暴露可能有助于预防 GBC。