Hui Cai1, Fei Ye2, Angelika Michel3, Gwen Murphy4, Shizuka Sasazuki5, Philip R Taylor4, You-Lin Qiao6, Sue K Park7, Keun-Young Yoo8, Sun Ha Jee9, Eo Rin Cho9, Jeongseon Kim10, Sheau-Chiann Chen2, Christian C Abnet4, Shoichiro Tsugane5, Qiuyin Cai1, Xiao-Ou Shu1, Wei Zheng1, Michael Pawlita3, Meira Epplein11. 1. Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center. 2. Vanderbilt Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DFKZ), Heidelberg, Germany. 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. 5. Epidemiology and Prevention Group, National Cancer Center, Tokyo, Japan. 6. Department of Cancer Epidemiology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 7. Cancer Research Institute, Department of Biomedical Sciences and Department of Preventive Medicine. 8. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. 9. Department of Epidemiology and Health Promotion, Institute for Health Promotion, Yonsei University, Seoul, Korea. 10. Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea. 11. Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center meira.epplein@vanderbilt.edu.
Abstract
BACKGROUND: Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea. METHODS: This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts. CONCLUSIONS: We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.
BACKGROUND: Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea. METHODS: This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts. CONCLUSIONS: We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.
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