Helicobacter pylori infection reduces likelihood of death from advanced cancer: A longitudinal analysis from the Japanese DAIKO prospective cohort study
Authors: Nishizuka Satoshi S. , Nakatochi Masahiro , Koizumi Yuka , Hishida Asahi , Okada Rieko , Kawai Sayo , Sut­oh Yoichi , Koeda Keisuke , Shimizu Atsushi , Naito Mariko , Wakai Kenji 
Published: December 2021

Background

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. Present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-.

Methods and findings

Prospective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) was used to assess whether anti-HP antibody status as a surrogate for past-present HP infection was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 34-69 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; 99.97%). The number of HP+ and HP- individuals was 1,826 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. To remove confounding factors associated with birth year, a birth year-matched cohort (n = 3,376) was generated for subsequent analyses. 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). Strikingly, we found that HP+ individuals who developed cancer had a better survival rate than would be expected based on cancer incidence. These results suggest that cancer patients who are HP+ may have a higher likelihood of survival than those who are HP-. 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.

Conclusions

Potential systemic effects of HP+ status may contribute to reduced likelihood of death for patients with cancer.

Data Availability Statement

The data cannot be shared publicly as data sharing is not permitted according to Japanese Government data protection policies. Requests for data analysis may be accepted anonymously and conditionally upon IRB approval from Iwate Medical University and Nagoya University Graduate School of Medicine.

Funding

This study is supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (No. 17015018); Grants-in-Aid for Innovative Areas (No. 221S0001); and the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 19K09130 and No. 16H06277 [CoBiA]) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests

The authors declare that no competing interests exist.

Author summary

Why was this study done?

> Although HP infection is a major cause of gastric diseases including cancer, how HP infection affects prolonged survival of advanced gastric cancer patients is unknown.

> Reports of studies carried out in different countries and regions revealed that advanced gastric cancer patients who are HP+ exhibited prolonged post-treatment survival, even though the genetic background of patients, HP strains, and cancer treatment procedures differed.

> Since most advanced gastric cancer patients underwent gastrectomy, the favorable prognosis of HP+ patients after multidisciplinary treatment may be due to putative systematic mechanisms associated with HP infection.

> If putative systemic mechanisms associated with HP infection reduce the likelihood of death due to cancer, the cancer survival rate in the HP+ population should be lower than that for the HP- population.

What did the researchers do and find?

> Using data from the DAIKO prospective cohort study in Nagoya, Japan, we analyzed the association between anti-HP antibody status, cumulative cancer incidence and all-cause and cancer-specific deaths.

> The HP+ rate increased as birth year decreased. Thus, matching based on birth year between 1935 and 1975 was performed to correct for confounding factors associated with birth year.

> Despite a significantly higher all-cancer incidence for HP+ individuals compared to those who were HP-, no difference in the all-cause and cancer death rate was observed between HP+ and HP- individuals.

What do these findings mean?

> HP+ individuals are less susceptible to death relative to their incidence of cancer.

> Patients with advanced stage cancer who are HP+ may have a better treatment response/tolerance than those who are HP-.

> Additional longitudinal analyses are warranted to evaluate the effect of HP+ status on prolonged survival of patients with advanced-stage cancer.