Research Article How Long Will It Take to Reduce Gastric Cancer Incidence by Eradicating Helicobacter Pylori Infection? John F. Osborn 1 , Maria S. Cattaruzza 1 , Anna M. Ferri 1 , Flora De Angelis 1 , Davide Renzi 1 , Alessandra Marani 1 , and Dino Vaira 2 Abstract Helicobacter pylori (H. pylori) is the most important risk factor for the development of gastric cancer. The objective of this article is to estimate how the number of clinically diagnosed cases caused by H. pylori would reduce in the years after the eradication of the infection from a population. It is assumed that the eradication of H. pylori will prevent the start of some new gastric tumors, but those that have passed the "point of no return" will continue to develop until diagnosed clinically. The observed reduction in the number of clinically diagnosed cases of gastric cancer will depend on the form and parameters of the distribution of the time t taken for tumor to develop into a clinical case after passing the "point of no return." This analysis assumes that the time t follows normal and log-normal distributions with means 5, 10, and 15 years. If the mean value of time t were 5 years, H. pylori caused cases should be almost eliminated after 10 years, whereas if the mean were 10 years, the number of cases should be halved. If the mean were 15 years, the reduction would only be about 15% after 10 years. The eradication of H. pylori from a population will reduce the incidence of gastric cancer, but the follow-up time needed to show and evaluate the reduction may be longer than that that has been used in studies published so far. Cancer Prev Res; 6(7); 695–700. Ó2013 AACR. Introduction Gastric cancer is the fourth highest incident cancer in the world and it is the second highest cause of cancer death. There were an estimated 989,000 new cases and 737,000 deaths worldwide in 2008 (1). Knowledge of the etiology and epidemiology of gastric cancer has changed dramatically since infection with Heli- cobacter pylori (H. pylori) was identified as its main risk factor and cause (2, 3). Although the role of H. pylori had been hypothesized 20 years before, it was only in 2005 that the Nobel Prize in Physiology or Medicine was awarded jointly to B.J. Marshall and J.R. Warren for their discovery of "the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease" (4). By the time they received their prize, much more was known about the harmful conse- quences of H. pylori infection and research after the early 1980s led the International Agency for Research on Cancer (IARC) to classify H. pylori as carcinogenic for humans in 1994 (5). Other important risk factors for gastric cancer include smoking, diet, occupation, and radiation. That the main risk factor is an infectious agent, is not novel; human papillomavirus is a cause of cervical cancer and there are campaigns for the vaccination of pubertal girls to prevent it. There are no similar campaigns for the treatment of H. pylori infection to prevent gastric cancer yet. Indeed, the evidence to show that the eradication of H. pylori can prevent gastric cancer obtained from single clinical trials is not particularly convincing. There have been few randomized controlled trials, and those that have been published relate to areas with very high prevalence of H. pylori infection. A meta-analysis (6) of 7 trials included 4 trials from China, 2 from Japan, and only 1 outside Asia, from Colombia. This meta-analysis evaluated a total of 6,695 participants and produced an overall relative risk of 0.65 (95% CI, 0.43–0.98). The result is statistically significant, but the confidence interval is wide. This is because, even though the total number of participants is large, there were only 37 cases in the treated groups and 56 among the controls. The median follow-up time was only 6 years with a range from 3 to 10 years. This study has been criticized because one study was included twice (7), but the authors of the original meta-analysis re-analyzed the data excluding the duplicated data obtaining very similar results, OR ¼ 0.65 (95% CI, 0.42–1.01). Furthermore, an analysis of one of the included studies was re-evaluated extending the follow-up to 14.7 years and concluded that H. pylori erad- ication reduced gastric cancer incidence (OR ¼ 0.61; 95% CI, 0.38–0.96; ref. 8). However, given the low incidence of gastric cancer and thus the long period of follow-up neces- sary to accrue a sufficient number of cases, and the ethical issues involved with recruiting infected individuals who may be randomized to receive a placebo, it may be that the randomized clinical trial is not necessarily the most Authors' Affiliations: 1 Department of Public Health and Infectious Dis- eases, Sapienza University of Rome, Rome; and 2 Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy Corresponding Author: John F. Osborn, Department of Public Health and Infectious Diseases, Room 31, Sapienza University of Rome, 5 P.le A. Moro, 00185 Rome, Italy. Phone: 39-06-4991-4881; Fax: 39-06-4991-4881; E-mail: john.osborn@uniroma1.it doi: 10.1158/1940-6207.CAPR-12-0428 Ó2013 American Association for Cancer Research. 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