Anti- <i>Helicobacter pylori</i> antibody status is associated with cancer mortality: A longitudinal analysis from the Japanese DAIKO prospective cohort study

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Abstract

Paradoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP ⁺) have a higher survival rate than those who are HP ^-. This finding suggests that HP infection has beneficial effects for cancer treatment. The present study examines whether HP ⁺ individuals have a lower likelihood of death from cancer than those who are HP ^-. Prospective cohort data ( n = 4,982 subjects enrolled in the DAIKO study between 2008–2010) were used to assess whether anti-HP antibody status was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 35–69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.98%). The number of HP ⁺ and HP ^- individuals was 1,825 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP ⁺ rates. With a birth year-matched cohort ( n = 3,376), all-cancer incidence was significantly higher in HP ⁺ individuals than those who were HP ^- (p = 0.00328), whereas there was no significant difference in the cancer death rate between HP ⁺ and HP ^- individuals (p = 0.888). Cox regression analysis for prognostic factors revealed that the hazards ratio of HP ⁺ was 1.59-fold (95%CI 1.17–2.26) higher than HP ^- in all-cancer incidence. Potential systemic effects of HP ⁺ status may contribute to reduced likelihood of death for patients after an initial diagnosis of cancer.

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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015

Christina Fitzmaurice, Christine Allen, Ryan M Barber … (2017)

IMPORTANCE Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (−6.1% [95% uncertainty interval (UI), −10.6% to −1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

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An immunogenic personal neoantigen vaccine for patients with melanoma

Patrick A. Ott, Zhuting Hu, Derin B. Keskin … (2017)

Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules. We hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoural balance in favour of enhanced tumour control. Here we demonstrate the feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumour neoantigens. Vaccine-induced polyfunctional CD4+ and CD8+ T cells targeted 58 (60%) and 15 (16%) of the 97 unique neoantigens used across patients, respectively. These T cells discriminated mutated from wild-type antigens, and in some cases directly recognized autologous tumour. Of six vaccinated patients, four had no recurrence at 25 months after vaccination, while two with recurrent disease were subsequently treated with anti-PD-1 (anti-programmed cell death-1) therapy and experienced complete tumour regression, with expansion of the repertoire of neoantigen-specific T cells. These data provide a strong rationale for further development of this approach, alone and in combination with checkpoint blockade or other immunotherapies.

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Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.

Mitsuru Sasako, Shinichi Sakuramoto, Hitoshi Katai … (2011)

The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.

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Author and article information

Contributors

Satoshi S. Nishizuka:

ORCID: https://orcid.org/0000-0001-9178-790X

Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing

Masahiro Nakatochi:

ORCID: https://orcid.org/0000-0002-1838-4837

Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing

Yuka Koizumi: Role: Visualization

Asahi Hishida:

ORCID: https://orcid.org/0000-0002-4867-0201

Role: Data curationRole: Project administration

Rieko Okada:

ORCID: https://orcid.org/0000-0002-6206-2501

Role: Data curationRole: Project administration

Sayo Kawai: Role: Data curationRole: Project administration

Yoichi Sutoh: Role: Methodology

Keisuke Koeda: Role: Funding acquisition

Atsushi Shimizu: Role: Methodology

Mariko Naito:

ORCID: https://orcid.org/0000-0003-3794-2643

Role: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing

Kenji Wakai: Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – review & editing

Ben Pascoe: Role: Editor

Journal

Journal ID (nlm-ta): PLOS Glob Public Health

Journal ID (iso-abbrev): PLOS Glob Public Health

Journal ID (publisher-id): plos

Title: PLOS Global Public Health

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 2767-3375

Publication date (Electronic): 8 February 2023

Publication date Collection: 2023

Volume: 3

Issue: 2

Electronic Location Identifier: e0001125

Affiliations

[1 ] Division of Biomedical Research & Development, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan

[2 ] Department of Integrated Health Sciences, Public Health Informatics Unit, Nagoya University Graduate School of Medicine, Nagoya, Japan

[3 ] Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

[4 ] Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

[5 ] Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Yahaba, Japan

[6 ] Department of Medical Safety Science, Iwate Medical University School of Medicine, Yahaba, Japan

[7 ] Division of Biomedical Information Analysis, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan

[8 ] Department of Oral Epidemiology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

University of Oxford, UNITED KINGDOM

Author notes

The authors declare that no competing interests exist.

* E-mail: snishizu@ 123456iwate-med.ac.jp

Author information

Satoshi S. Nishizuka https://orcid.org/0000-0001-9178-790X

Masahiro Nakatochi https://orcid.org/0000-0002-1838-4837

Asahi Hishida https://orcid.org/0000-0002-4867-0201

Rieko Okada https://orcid.org/0000-0002-6206-2501

Mariko Naito https://orcid.org/0000-0003-3794-2643

Article

Publisher ID: PGPH-D-22-00552

DOI: 10.1371/journal.pgph.0001125

PMC ID: 10022139

PubMed ID: 36962964

SO-VID: 144b757e-b76a-4452-bf4a-fcd81bd860ba

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 1 April 2022

Date accepted : 22 December 2022