飲食致癌物導致HP感染者胃癌發生增多

致命的合作: 幽門螺桿菌與泡菜或燻肉By some estimates, more than 50% of the world‘s population is infected by the bacterium Helicobacter pylori, a gastrointestinal pathogen most famous for its role in the development of gastric ulcers. H. pylori infection is also a risk factor for gastric cancer, but because only a small percentage of infected individuals develop the disease, it would be of great interest to identify controllable lifestyle factors that might contribute to an enhanced risk of cancer. Correlative data from epidemiological studies have suggested a potential interaction between H. pylori infection and diet, but long-term human studies that would establish a cause-effect relationship are not feasible.
據估計，全世界超過50%的人口都受到了幽門螺旋桿菌（HP）的感染，HP是一種一種胃腸道病原體，因可引發胃潰瘍而爲大衆所知。HP感染也是胃癌的一個風險因素，但由於感染者中只有小比例的人會患上胃癌，因此是否因爲某種生活方式提高了患癌風險的問題引起很多研究者關注。現有流行病學的相關數據顯示在HP和飲食之間有着潛在的相互作用，但是以建立一種因果關係爲目的的長期的人類學研究是不可行的。In a carefully controlled 5-year study of Rhesus monkeys that were monitored at frequent intervals by gastroscopy and biopsy, Liu et al. found that gastric neoplasia (precancerous and cancerous lesions) developed in H. pyloriCinfected animals that had also consumed a carcinogen similar to one found in pickled vegetables and smoked meats, but not in animals exposed to either the bacterium or the carcinogen alone. In terms of cancer prevention strategies, these findings underscore the importance of dietary awareness in individuals known to be infected with H. pylori.
在一項爲期5年的關於恆河猴的對照研究中，通過多次間隔性的胃掃描和活體組織檢查監測研究，研究者發現在受到HP感染，而且飲食中又包含了一種與在泡菜和燻肉中發現的致癌物相似的致癌物的動物身上出現了胃部腫瘤（癌前或癌性病變），但是那些僅感染了HP或是僅接受含致癌物餵食的動物並沒有發生胃癌。在癌症預防策略方面，這些研究結果突出表明了飲食因素對HP感染者的重要性。原文出處
Liu H, Merrell DS, Semino-Mora C, Goldman M, Rahman A, Mog S, Dubois A. Diet Synergistically Affects Helicobacter pylori-Induced Gastric Carcinogenesis in Nonhuman Primates.Gastroenterology. 2009 Jul 19.文摘
BACKGROUND & AIMS: Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys.
背景和目的： HP感染，含致癌物飲食以及缺陷基因等綜合作用可能誘導胃部腫瘤，這些因素在胃癌發病中的作用尚不能在人體上進行驗證性的研究，本研究以恆河猴爲對象對一種口服的致癌物與HP感染這兩種因素進行了研究。METHODS: Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; and inoculation of a virulent H pylori strain alone (H), or in combination with ethyl-nitro-nitrosoguanidine (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies.
方法： 23只恆河猴，分爲4組，分別爲：對照組，單獨餵食N-乙基-N’-硝基-亞硝基胍(ENNG)組（E組），單獨接種了HP的感染組（H組），以及HP感染+ENNG餵食組（EH組）。在爲期5年的病理學和分子學研究中，每隔3個月進行一次胃鏡檢查和活體組織檢查。RESULTS: Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsies at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer.
結果：在接種HP受到感染後，H組和HE組都表現出持續的感染和竇性胃炎症狀。分別在第二年和第五年，EH組中的3只恆河猴患上了胃腸道腫瘤和上皮內瘤變，而其他組沒有發現。第五年的活檢轉錄分析顯示EH組的種特異性表達有着顯著改變，腫瘤特異性表達發現多個與腫瘤相關的基因表達有改變。重要的是，在非腫瘤性的胃粘膜上的明顯的腫瘤性變異，顯示了被標識的基因可能是前期胃癌的代表性標記。CONCLUSIONS: Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosamines found in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates.
結論：HP感染配合餵食與泡菜和燻肉中相似的致癌物誘導了胃部腺內腫瘤，提示HP和該致癌物對恆河猴胃部腫瘤的協同誘導作用。