Family History of Gastric Cancer and Helicobacter pylori Treatment.

BACKGROUND Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

[1]  C. O'Morain,et al.  Helicobacter pylori Infection , 1994 .

[2]  P. Malfertheiner,et al.  Kyoto global consensus report on Helicobacter pylori gastritis , 2015, Gut.

[3]  D. Graham,et al.  Houston Consensus Conference on Testing for Helicobacter pylori Infection in the United States , 2018, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[4]  L. Murray,et al.  Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori. , 2000, Gastroenterology.

[5]  M. Gail,et al.  Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial , 2019, BMJ.

[6]  M F Dixon,et al.  Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. , 1996, The American journal of surgical pathology.

[7]  S. Leung,et al.  Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. , 2004, JAMA.

[8]  I. Choi,et al.  Effectiveness of the Korean National Cancer Screening Program in Reducing Gastric Cancer Mortality. , 2017, Gastroenterology.

[9]  Nayoung Kim,et al.  Stomach Cancer Risk in Gastric Cancer Relatives: Interaction Between Helicobacter pylori Infection and Family History of Gastric Cancer for the Risk of Stomach Cancer , 2010, Journal of clinical gastroenterology.

[10]  Stanley R. Hamilton,et al.  Pathology and genetics of tumours of the digestive system , 2000 .

[11]  R. Hunt,et al.  Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials , 2014, BMJ : British Medical Journal.

[12]  I. Choi,et al.  Effect of repeated endoscopic screening on the incidence and treatment of gastric cancer in health screenees , 2009, European journal of gastroenterology & hepatology.

[13]  H. Algood,et al.  Temporal Control of the Helicobacter pylori Cag Type IV Secretion System in a Mongolian Gerbil Model of Gastric Carcinogenesis , 2020, mBio.

[14]  J. G. Kim,et al.  Treatment of Helicobacter pylori Infection in Korea: A Systematic Review and Meta-analysis , 2015, Journal of Korean medical science.

[15]  I. Choi,et al.  Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer , 2018, The New England journal of medicine.

[16]  Nayoung Kim,et al.  Gastric cancer and family history , 2016, The Korean journal of internal medicine.

[17]  R. Hunt,et al.  Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report , 2016, Gut.

[18]  M. Gail,et al.  Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. , 2012, Journal of the National Cancer Institute.

[19]  Does Helicobacter pylori eradication therapy to prevent gastric cancer increase all‐cause mortality? , 2018, International journal of cancer.

[20]  M. Gail,et al.  Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. , 2014, Journal of the National Cancer Institute.

[21]  I. Choi,et al.  Helicobacter pylori infection and histological changes in siblings of young gastric cancer patients , 2011, Journal of gastroenterology and hepatology.

[22]  W. Chey,et al.  ACG Clinical Guideline: Treatment of Helicobacter pylori Infection , 2017, The American Journal of Gastroenterology.

[23]  Kyu-Won Jung,et al.  Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2015 , 2018, Cancer research and treatment : official journal of Korean Cancer Association.

[24]  R. P. Blankfield,et al.  Helicobacter pylori infection and the development of gastric cancer. , 2001, The New England journal of medicine.

[25]  M. Blaser,et al.  Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. , 1991, The New England journal of medicine.

[26]  M. Vieth,et al.  A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication , 2015, Gut.

[27]  G. Friedman,et al.  Helicobacter pylori infection and the risk of gastric carcinoma. , 1991, The New England journal of medicine.

[28]  J. Moon,et al.  Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients , 2002, International journal of cancer.

[29]  M. Gail,et al.  Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. , 2006, Journal of the National Cancer Institute.

[30]  K. Jung,et al.  Geographical Variations and Trends in Major Cancer Incidences throughout Korea during 1999-2013 , 2018, Cancer research and treatment : official journal of Korean Cancer Association.

[31]  I. Choi,et al.  Association of family history with cancer recurrence and survival in patients with gastric cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  R. Hunt,et al.  What is the quantitative risk of gastric cancer in the first-degree relatives of patients? A meta-analysis , 2017, World journal of gastroenterology.

[33]  S. Ng,et al.  Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. , 2017, Gastroenterology.

[34]  D. Beall.  Classification and Grading of Gastritis: The Updated Sydney System , 1997 .

[35]  H. Brenner,et al.  Helicobacter pylori infection among offspring of patients with stomach cancer. , 2000, Gastroenterology.

[36]  D. Albanes,et al.  Family history of cancer in first-degree relatives and risk of gastric cancer and its precursors in a Western population , 2018, Gastric Cancer.

[37]  M. Carrington,et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer , 2000, Nature.

[38]  M F Dixon,et al.  The Vienna classification of gastrointestinal epithelial neoplasia , 2000, Gut.