Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk.

Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk.
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DOI:
10.1136/gut.2010.234468
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发表时间:
2011-09
期刊:
Gut
影响因子:
24.5
通讯作者:
Wilson KT
Wilson KT
中科院分区:
医学1区
文献类型:
--
作者:
de Sablet T;Piazuelo MB;Shaffer CL;Schneider BG;Asim M;Chaturvedi R;Bravo LE;Sicinschi LA;Delgado AG;Mera RM;Israel DA;Romero-Gallo J;Peek RM Jr;Cover TL;Correa P;Wilson KT

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幽门螺杆菌在一半人的胃中定居,是导致胃癌的主要原因,而胃癌是全球癌症死亡的第二大原因。虽然胃癌的发病率与某些地区幽门螺杆菌的患病率相关,但有些地区的感染几乎是普遍的,但胃癌的发病率很低。以哥伦比亚为例,安第斯山区(高风险)的胃癌发病率比沿海地区(低风险)高25倍,尽管这两个地区的幽门螺杆菌患病率同样高(约90%)。我们的目的是调查从这些高风险和低风险地区的受试者中分离的幽门螺杆菌菌株的祖先起源,并确定这是否是癌前病变的预测决定因素。采用多位点序列分型方法,对从哥伦比亚Nariño州太平洋沿岸和安第斯山脉分离的感染幽门螺杆菌菌株进行系统地理起源调查。我们分析了64例感染cagA+ vacA s1m1菌株的受试者。对每个个体的胃活检切片进行组织学病变评分,并通过免疫组织化学评估DNA损伤。我们发现,来自高风险地区的毒株均来自欧洲,而来自低风险地区的毒株要么来自欧洲(34%),要么来自非洲(66%)。即使在低风险地区,欧洲菌株起源也能强烈预测癌前组织学病变和上皮DNA损伤的增加;非洲毒株起源与这些参数的严重程度降低有关。幽门螺杆菌菌株的系统地理学起源为这种感染引起的癌症风险的地理差异提供了解释。
Helicobacter pylori colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with H. pylori prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (~90%) H. pylori prevalence in the two locations. Our aim was to investigate the ancestral origin of H. pylori strains isolated from subjects in these high and low risk regions and to determine whether this is a predictive determinant of precancerous lesions. Multi-locus sequence typing was used to investigate phylogeographic origins of infecting H. pylori strains isolated from subjects in the Pacific coast and Andean mountains in the state of Nariño, Colombia. We analysed 64 subjects infected with cagA+ vacA s1m1 strains. Gastric biopsy slides from each individual were scored for histologic lesions and evaluated for DNA damage by immunohistochemistry. We show that strains from the high risk region were all of European phylogeographic origin, whereas those from the low risk region were of either European (34%) or African origin (66%). European strain origin was strongly predictive of increased premalignant histologic lesions and epithelial DNA damage, even in the low risk region; African strain origin was associated with reduced severity of these parameters. The phylogeographic origin of H. pylori strains provides an explanation for geographic differences in cancer risk deriving from this infection.
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