Neglected role of hookah and opium in gastric carcinogenesis: A cohort study on risk factors and attributable fractions

Gastric cancer holds a special place among worldwide malignancies in terms of both mortality and incidence. It constitutes the fourth common cause of cancer incidence and the second cause of cancer-related death. Gastric cancer is the first and third most common cancer in Iranian men and women, respectively. Ardabil province, located to the west of the Caspian Sea littoral, has one of the highest worldwide incidence rates of gastric cancer and a rising trend compared to previous reports

The classic pathogenesis of noncardia, and a group of cardia, cancers follows a slow progression from chronic gastritis through atrophic gastritis and intestinal metaplasia to dysplasia and eventually, adenocarcinoma. Although Helicobacter pylori (H. pylori) is essential for initiation of the cascade, remarkable geographical variations in gastric cancer incidence suggest a potential role for other lifestyle and genetic risk factors in the course of this malignancy. Current knowledge on lifestyle and dietary factors of gastric cancer leaves no doubt about the role of well-established factors including excess salt intake, low intake of fresh fruit/vegetable and smoking

Several studies have reported associations between opium and different malignancies, namely esophagus, bladder, lung and larynx. A recent study showed a higher risk of gastric cancer associated with opium. Hookah, a traditional smoking instrument in the Middle East, is another possible risk factor for gastric cancer and reportedly growing among younger populations of Western countries. Although largely believed by the public to be less harmful than cigarettes, the report by Shakeri et al. suggests hookah's association with gastric cancer in Iran. On the basis of the growing epidemiological evidence on the role of opium and hookah, and lack of mechanistic studies on the topic, the World Health Organization has encouraged further research on hookah/opium association with malignancies, including gastric canc

We aimed to investigate the factors associated with gastric caner and precancerous lesions, including hookah and opium as neglected risk factors, in a follow-up study of H. pylori-infected subjects. As our study is one of the few investigations with baseline histological information, we could evaluate the association between precancerous lesions (atrophic gastritis and intestinal metaplasia) and lifestyle risk factors. Second, we could study the impact of precancerous lesions and lifestyle risk factors on the development of gastric cancer in H. pylori-infected subjects. Additionally, our cohort findings enabled us to calculate the fraction of incident cancers attributable to each preventable risk factor (attributable fraction, AF)

Material and Methods

Study population

This population-based follow-up study took place in Ardabil province, Northwest Iran. Participants were chosen through random selection from permanent residents of urban and rural areas in Ardabil (province capital) and Meshkinshahr townships, who were aged 40 years or more. The exclusion criteria were participant's refusal, known gastrointestinal, cardiac or respiratory disease and pregnancy. Mild dyspepsia symptoms without a definite prescription by a physician were not an exclusion criterion. Participants were informed about the risks and benefits of the study and signed the informed consent forms. Out of 1,122 subjects invited, 1,011 (91.5%) consented to endoscopy. As all cancer patients were H. pylori positive, for our analysis, we only included those 928 (91.8%) participants infected with H. pylori, based on a positive test result in either histology or rapid urease test

Follow-up

The participants were followed for 10 years by Aras Clinic, which is properly equipped for diagnosis and treatment of gastrointestinal disorders and has sufficient facilities for preservation of biologic specimen. National and local cancer and death registries contributed to the follow-up process. Authors regularly searched the relevant cancer and death registries to extract the time of gastric cancer events. Trained physicians directly contacted all participants (or their next of kin) for whom no records were found in above registries to determine their health status

Results

Nine hundred and twenty-eight participants included in our study (49.1% men) were followed up for an average of 121.8 months (range: 10–132 months), during which 121 (13.0%) subjects died, and 42 (4.5%) subjects were lost to follow-up. Participants were followed up for a total duration of 9,096 person-years, during which 36 participants were diagnosed with gastric cancer, yielding an incidence rate of 3.96/1,000 persons per year