Helicobacter Pylori, antioxidants and garlic in stomach cancer prevention

Relation

Li WQ, Zhang JY, Ma JL, et al. Effects ofHelicobacter pyloriTreatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial.BMJ. 2019;366:15016

Draft

Blinded, randomized, factorial, placebo-controlled study (Shandong Intervention Trial)

Objective

To determine whether the eradication ofHelicobacter pyloriand/or garlic and/or vitamin (vitamin C, vitamin E, and selenium) supplementation affect gastric cancer incidence or mortality over a period of just over 2 decades (22.3 years)

Participant

The participants are those in the Shandong Intervention Trial. In 1994, 3,599 people volunteered for the study, including undergoing gastroscopy with biopsies and providing blood samplesHelicobacter pyloritest. All participants were from 13 villages in Linqu, China, a region with a high incidence of gastric cancer. After all exclusion criteria were applied, a total of 3,365 participants (aged 35-64) were followed and assessed.

intervention

Of the total 3,365 participants, 2,258 were seropositive for IgG antibodiesHelicobacter pyloriand 1,107 were not. Each group received either a sham treatment forHelicobacter pylorior correctHelicobacter pyloriEradication treatment as well as a 2 x 2 allocation to vitamin and garlic supplement arms. The details of the groups are as follows:

• Vom 15. September 1995 bis zum 29. November 1995 erhielt die seropositive Gruppe (n = 2.258) 1 g Amoxicillin und 20 mg Omeprazol (n = 1.130) oder ein Placebo-Äquivalent (n = 1.128) zweimal täglich für 2 Wochen. Während dieser Zeit erhielten diejenigen, die seronegativ waren (n = 1.107), ein Placebo, um die Maskierung aller Teilnehmer aufrechtzuerhalten.
• Von Januar bis März 1996, ¹³Cure-Harnstoff-Atemtests zeigten, dass 382 Teilnehmer immer noch seropositiv waren, und diese Teilnehmer erhielten eine zusätzliche zweiwöchige Behandlung mit Amoxicillin und Omeprazol. Um die Maskierung der Teilnehmer aufrechtzuerhalten, wurden 383 Teilnehmer nach Geschlecht, Dorf und Alter abgeglichen und erhielten eine Placebo-Behandlung.
• Vom 30. November 1995 bis zum 31. März 2003 erhielten alle Teilnehmer (n = 3.365) randomisiert zweimal täglich entweder eine Vitaminkapsel (n = 1.677) oder ein identisch aussehendes Placebo (n = 1.688). Jede Kapsel des Vitaminpräparats enthielt 250 mg Vitamin C, 100 IE Vitamin E und 37,5 µg Selen.
• Vom 30. November 1995 bis zum 31. März 2003 wurden alle Teilnehmer (n = 3.365) nach dem Zufallsprinzip ausgewählt, um zweimal täglich 1 Kapsel Knoblauch-Ergänzung oder Placebo einzunehmen. Das Knoblauchpräparat (verwendete Marke: Waukanuga) enthielt 200 mg gealterten Knoblauchextrakt und 1 mg dampfdestilliertes Knoblauchöl pro Kapsel. Placebo-Flaschen enthielten winzige Mengen Knoblauchöl, um die Zuordnung zu maskieren.

Patient compliance was considered excellent, with follow-up of supplement intake by pill counting at monthly visits for 7.3 years of supplementation. All supplements and placebos were completed on March 31, 2003. Records of gastric cancer incidence and causes of death for study participants were continued throughout the 22.3-year follow-up period, which ended December 1, 2017.

Parameters evaluated

The primary endpoint was the incidence and mortality of gastric cancer over the course of the study (22.3 years). The authors suspect an incidence due to planned gastroscopy and active clinical follow-up. They determined stomach cancer-related mortality from official records, including death certificates and hospital records.

Secondary endpoints included other causes of death, including other cancers and cardiovascular disease.

Result

Primary endpoint: From 1995 to 2017, there were 151 cases of stomach cancer and 94 deaths from the disease.

Key insights

All 3 interventions were associated with a significant reduction in gastric cancer mortality. The adjusted hazard ratios were 0.62 (95% CI; 0.39-0.99) forHelicobacter pylorieradication, 0.48 (0.31–0.75) for vitamin supplementation and 0.66 (0.43–1.00) for garlic supplementation.

In this analysis, 22.3 years after participants were randomized,Helicobacter pyloriEradication resulted in reduced incidence, vitamin supplementation resulted in reduced incidence, and garlic supplementation did not reach statistical significance in gastric cancer incidence.

Regarding the secondary endpoints, there were no measurable effects between the interventions and other cancers or cardiovascular diseases in this study.

comment

Stomach cancer is the fifth most common cancer worldwide and the third most common cause of cancer death after lung and colon cancer.¹Globally, incidence varies greatly by culture and region, with the highest incidence rates in East and Central Asia and Latin America. In North America the incidence is relatively low at 5.6/100,000 of the population.¹Given the genetic predisposition to gastric cancer, a higher clinical suspicion is warranted in individuals with gastric problems of Asian or Latino descent.²

The overall incidence of stomach cancer is declining, even before the introduction ofHelicobacter pyloriExtermination. In particular, non-cardiac gastric cancer, which affects the lower part of the stomach, is declining. This is believed to be due to changes in hygiene, food preservation techniques and greater availability of fresh fruits and vegetables.³Lastly, extermination ofHelicobacter pyloriwhich is associated with atrophic gastritis and a higher risk of gastric cancer, has led to a further decline in the incidence of non-cardiac gastric cancer.

While the incidence of non-cardia gastric cancer has decreased, cardia gastric cancer, which is similar to esophageal cancer, has increased sevenfold. The reasons for this are unclear, but central obesity with subsequent hiatal hernia and reflux are implicated.⁴In addition, cardia is often not stomach cancerHelicobacter pylori-tied together.

The Shandong Intervention Study began in 1994 and was an ongoing study with multiple follow-up time points to assess the temporal effects of the interventions.⁵This study is also a landmark study in oncology, showing for the first time that eradication ofHelicobacter pyloriInfection lowers the incidence of stomach cancer.^6.7The extermination ofHelicobacter pyloriis now a recognized strategy for reducing the risk of stomach cancer worldwide.⁸Ongoing studies continue to identify the best ways to create community-wide programs to reduce the incidence of stomach cancerHelicobacter pyloriExtermination.^9.10

Two previous time points used for data analysis of the Shandong study were 7.3 years after randomization and 14.7 years after randomization. The current study took place 22.3 years after randomization. The data from all of these created a temporal perspective of the interventions used in the study. A key finding of this study is the confirmation that the eradication ofHelicobacter pyloriwith a treatment period of just 2-4 weeks, significantly reduces both the incidence and mortality of gastric cancer in the following 20+ years.

Vitamin supplementation tended to result in lower gastric cancer incidence and mortality, but did not achieve a statistically significant reduction in incidence and mortality until 22.3 years. Garlic supplementation did not achieve a statistically significant reduction in gastric cancer incidence at any time point, but after 22.3 years, garlic resulted in a statistically significant reduction in gastric cancer mortality. This suggests that time-limited treatment with vitamins or garlic (7.3 years, from 1995 to 2003) influenced the incidence and mortality of gastric cancer more than 2 decades later.

restrictions

Data on self-prescribed or doctor-prescribed treatments, inclHelicobacter pylori–directed therapies were no longer pursued after 2003. Lifestyle, diet and supplement intake were also no longer tracked after 2003 and are unlikely to change the results.

This population was known to be deficient in nutrients, particularly vitamin C and selenium, 2 of the nutrients in the vitamin supplement. However, since more than the daily requirement was administered as a dietary supplement, it is unclear whether it is a saturation or dose-dependent effect of the vitamins that played a role in reducing the incidence and mortality of gastric cancer. It also cannot be determined whether adding these nutrients will benefit those who are not deficient.

As is often the case, the authors conclude by suggesting that further studies need to be conducted before any of the therapeutic interventions are adopted into community medicine. However, it is clinically difficult to justify patients not being provided with vitamin C, selenium and vitamin E while enjoying garlic in their diet. Once again we have reason to encourage the adoption of a highly plant-based diet, with another study suggesting that allium garlic in particular is beneficial. As more studies are conducted, we can be confident that this overall health-promoting advice will serve patients well and perhaps even reduce their risk of developing or dying from stomach cancer.