Esophageal cancer in northeastern Iran: a review

Golestan Province in northeastern Iran has one of the highest rates of esophageal squamous cell cancer in the world. This article reviews the studies conducted on esophageal squamous cell cancer in this area and summarizes the data on epidemiologic patterns, incidence trends, and etiology of esophageal squamous cell cancer in this province

[High exposure to polycyclic aromatic hydrocarbons may contribute to high risk of esophageal cancer in northeastern Iran]

The northeastern region of Iran has some of the highest rates of esophageal squamous cell carcinoma [ESCC] in the world. To investigate the role of polycyclic aromatic hydrocarbons [PAHs] in the etiology of ESCC in northeastern Iran, we measured urine 1-hydroxypyrene glucuronide [1-OHPG], a stable PAH metabolite, in 99 inhabitants of this area. Results: The median urine 1-OHPG in participants of this study was 4.2 pmol/ml. Forty-two subjects [42%] had levels ranging from 1 to 5 pmol/ml, indicative of moderate PAH exposure, and 41 [41%] had levels above 5 pmol/ml, indicative of very high exposure. Further analysis showed that 1-OHPG levels were high in all subgroups of our study subjects, including both sexes; rural and urban dwellers; and smokers and non-smokers. Only 15% of the variance in 1-OHPG was explained by age, sex, residence, smoking, nass, or opium consumption. This pattern of PAH exposure parallels with the ESCC incidence pattern seen in this area. We conclude that people in northeastern Iran are exposed to widespread and very high levels of PAH, largely from unknown sources, and this may contribute to the high rates of ESCC observed in this area

[Ecologic study of serum selenium and upper gastrointestinal cancers in Iran]

Both observational and experimental studies have shown that higher selenium status reduces the risk of upper gastrointestinal cancers in selenium deficient populations. Recent cancer registry data have shown very different rates of esophageal cancer [EC] and gastric cancer [GC] in four provinces of Iran, namely Ardabil, Mazandaran, Golestan, and Kerman. The aim of this study was to have a preliminary assessment of the hypothesis that high rates of EC in Golestan and high rates of GC in Ardabil may be partly attributable to selenium deficiency. We measured serum selenium in 300 healthy adults from Ardabil [n=100], Mazandaran [n=50], Golestan [n=100], and Kerman [n=50], using inductively coupled plasma, with dynamic reaction cell, mass spectrometry [ICP-DRC-MS] at the US Centers for Disease Control [Atlanta, Georgia]. The median serum selenium concentrations were very different in the four provinces. The medians [IQR] for selenium in Ardabil, Mazandaran, Golestan, and Kerman were 82 [75-94], 123 [111-132], 155 [141-173], and 119 [110 -128] micro g/L, respectively [p<0.001]. The results of linear regression showed that the province variable, by itself, explained 76% of the variance in log selenium [r2=0.76]. The proportion of the populations with a serum selenium more than 90 micro g/L [the concentration at which serum selenoproteins are saturated] was 100% in Golestan, Kerman, and Mazandaran but only 29% in Ardabil. Our findings suggest that selenium deficiency is not a major contributor to the high incidence of EC seen in northeastern Iran, but it may play a role in the high incidence of GC in Ardabil province

[Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population]

The role of human papillomavirus [HPV] in the etiology of esophageal squamous cell carcinoma [ESCC] is not clear. Previous studies have found highly variable [from 0% to 67%] prevalence of HPV in ESCC tumor. However, prevalence of HPV in ESCC tumor seems to be higher in areas with high incidence of ESCC, such as China and South Africa. Iran is one of the areas of the world with the highest rates of ESCC. However, no previous study has reported the prevalence of HPV in ESCC tumor tissues from Iran. In this study, we compared the prevalence of a common marker for the presence of HPV [MY09/MY11 consensus primers] and two markers for the presence of HPV-16 and HPV-18 [respective E6 /E7 primers] in tumor tissues from 38 ESCC cases and normal biopsied tissues from 38 Iranian individuals. 14 out of the 38 ESCC [36.8%] samples, but only 5 out of 38 control samples [13.2%] were positive for the common marker of HPV presence; this difference was statistically significant [p=0.02]. Five ESCC samples [13.2%] but none of the control samples were positive for HPV16 E6 /E7 gene [p=0.05]. Three of the ESCC samples [7.9%] and five of the control samples [13.2%] were positive for HPV18 E6 /E7 gene. Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor responsible for the increased incidence of ESCC in Iran and other high-incidence areas of the world