Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model

Abstract

Jennifer Yeh and colleagues examine the contribution of IHelicobacter pylori I and smoking trends to the incidence of past and future intestinal-type noncardia gastric adenocarcinoma.

Please see later in the article for the Editors' Summary

Abstract

Background

Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence.

Methods and Findings

We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%–58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%–21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%–100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.

Conclusions

Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Cancer of the stomach (gastric cancer) is responsible for a tenth of all cancer deaths world-wide, with an estimated 700,000 people dying from this malignancy every year, making it the second most common cause of global cancer-related deaths after lung cancer. Unfortunately, the projected global burden of this disease estimate that deaths from gastric cancer will double by 2030. Gastric cancer has a poor prognosis with only a quarter of people with this type of cancer surviving more than five years. In order to reduce deaths, it is therefore of utmost importance to identify and reduce the modifiable risk factors associated with gastric cancer. Smoking and chronic gastric infection with the bacteria Helicobacter pylori (H. pylori), are known to be two common modifiable risk factors for gastric cancer, particularly for a type of gastric cancer called intestinal-type noncardia gastric adenocarcinoma (NCGA), which occurs at the distal end of the stomach and accounts for more than half of all cases of gastric cancer in US men.

Why Was This Study Done?

H. pylori initiates a precancerous process, and so infection with this bacteria can increase intestinal-type NCGA risk by as much as 6-fold while smoking doubles cancer risk by advancing increasing progression of existing lesions. Changes in these two risk factors over the past century (especially following the US Surgeon General's Report on Smoking and Health in 1964) have led to a dramatic decline in the rates of gastric cancer in US men. Understanding the combined effects of underlying risk factor trends on health outcomes for intestinal-type NCGA at the population level can help to predict future cancer trends and burden in the US. So in this study, the researchers used a mathematical model to estimate the contribution of H. pylori and smoking trends on the decline in intestinal-type NCGA incidence in US men.

What Did the Researchers Do and Find?

The researchers used birth cohorts derived from data in two national databases, the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS) to develop a population-based model of intestinal-type NCGA. To ensure model predictions were consistent with epidemiologic data, the researchers calibrated the model to data on cancer and precancerous lesions and using the model, projected population outcomes between 1978 and 2040 for a base-case scenario (in which all risk factor trends were allowed to vary over time). The researchers then evaluated alternative risk factors scenarios to provide insights on the potential benefit of past and future efforts to control gastric cancer.

Using these methods, the researchers estimated that the incidence of intestinal-type NCGA (standardized by age) fell from 11.0 to 4.4 per 100,000 men between 1978 and 2008, a drop of 60%. When the researchers incorporated only H. pylori prevalence and smoking trends into the model (both of which fell dramatically over the time period) they found that intestinal-type NCGA incidence fell by only 28% (from 12.7 to 9.2 per 100,000 men), suggesting that H. pylori and smoking trends are responsible for 47% of the observed decline. The researchers found that H. pylori trends alone were responsible for 43% of the decrease in cancer but smoking trends were responsible for only a 3% drop. The researchers also found evidence that after the 1960s, observed trends in lower smoking initiation and higher cessation accelerated the decline in intestinal-type NCGA incidence by 7%. Finally, the researchers found that intestinal-type NCGA incidence is projected to decline an additional 47% between 2008 and 2040 (4.4 to 2.3 per 100,000 men) with H. pylori and smoking trends accounting for more than 80% of the observed fall.

What Do These Findings Mean?

These findings suggest that, combined with a fall in smoking rates, almost half of the observed fall in rates of intestinal-type NCGA cancer in US men between 1978 and 2008 was attributable to the decline in infection rates of H. pylori. Rates for this cancer are projected to continue to fall by 2040, with trends for both H. pylori infection and smoking accounting for more than 80% of the observed fall, highlighting the importance of the relationship between risk factors changes over time and achieving long-term reduction in cancer rates. This study is limited by the assumptions made in the model and in that it only examined one type of gastric cancer and excluded women. Nevertheless, this modeling study highlights that continued efforts to reduce rates of smoking and H. pylori infection will help to reduce rates of gastric cancer.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001451.

• The National Cancer Institute gives detailed information about gastric cancer

• The Gastric Cancer Foundation has information on gastric cancer for patients and professionals

• Cancer Research UK explains types of gastric cancer