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Oesophageal cancer (OC) is the eighth most common cancer worldwide, with an estimated 456,000 new cases in 2012 (3.2% of the total), and the sixth leading cause of cancer-related mortality, with an estimated 400,000 deaths (4.9% of the total). Survival after a diagnosis of OC remains poor, emphasising the pivotal role of primary prevention.
While alcohol and tobacco are important recognised risk factors for squamous cell OC (SCOC), the role of other potential risk factors is less clear. North-eastern Iran has long been known to have exceptionally high rates of OC (predominantly squamous cell).
However, unlike that seen in the United States and Europe, cigarette smoking and alcohol consumption are not major causes in this region. This peculiarity provides us with a unique opportunity to explore additional risk factors of SCOC.
Hypothesis and objectives
We hypothesize that characteristics of “unhealthy diet” (according to WCRF/AICR dietary score), in conjunction with chronic thermal irritation of oesophageal epithelium from hot tea (>65°C) and long-term exposure to a carcinogenic agent (opium components/products), are responsible for the very high incidence of OC in north-eastern Iran.
Settings and methods
We will conduct this project within the Golestan cohort study (GCS). The GCS has recruited 50,045 individuals, aged 40-75, from both rural (80%) and urban (20%) areas of Golestan province in north-eastern Iran. The proposed study will include 300 SCOC cases and 1,200 age-, sex- and residential place-matched controls from the GCS, using a nested case-control design.
In order to estimate the within-person variation of exposures, 150 control subjects will be selected from a sub-group of the control population who were interviewed twice. The main covariates will include: 1) a modified version of WCRF/AICR score (ranging from 0-4) from the Golestan food frequency questionnaire (FFQ); 2) health behaviours, including opium use (confirmed by urinary opium metabolites), tobacco use, and alcohol consumption; and 3) tea consumption habits including type, quantity, and temperature. For the main effect analyses, we will have sufficient statistical power (>80%) to detect moderate RRs of above 1.5.
Even outside of extremely high-risk regions like north-eastern Iran, unhealthy diet and hot drinks are suspected causes of OC. For example, multiple case-control studies in Europe have identified diets deficient in fruits and vegetables, as well as high consumption of tea, as being risk factors for OC.
However, the evidence from these retrospective case-control studies is subject to recall bias and uncontrolled confounding by tobacco smoking or alcohol drinking. Tobacco smoking and alcohol consumption are not however major causes of OC in north-eastern Iran. Furthermore, opium use is not stigmatised, and is practiced by about 20% of the adult population.
This unique prospective cohort therefore provides us with the opportunity to identify additional important risk factors of OC within this high-risk population, which will be relevant to north-eastern Iran as well as other high risk regions.