Table 1 . Summary of evidence about the association between environmental factors and ESCC .

Risk factors (RF)	Study Type (reference)		Association and risk (reference)
	Other region	Golestan	Other regions	Golestan
SES	-Population based case control study29	Population-based case control study 5, 27, 72	-Low annual incomes: AOR=4.3 for white people AOR=8.0 for black people -Incidence rate(exposure to the same RFs: black people>white people -Never married: OR=3.9 - Low educational: OR=3.1 - Low occupation: OR=4.2 -Low socioeconomic: OR= 1.8 29	-Compared with no education: primary education: AOR=0.52 ≥high school: AOR = 0.2027 -Residence in urban areas: HR:0.7 Non-Turkmen ethnic : HR=0.765 -No significant difference between Turkmen and non-Turkmen ESCC cases in the prevalence of exposure72
Smoking	-population based case control study 29	-Cross sectional3 -Case control24	Tobacco use in ESCC : OR:3.1 white males OR:2.5 black males 29	-Only 27% of ESCC patients had ever smoked (similar to other cancer and non-cancer groups) - OR=1.70; 95%CI:1.05-2.7324
Alcohol consumption	-Population based case control study 29	- Cross sectional 3 - Case control 24	It is main RF: OR:6.8 white males OR:8.3 black males 29	-Only one of the 144 ESCC cases had ever consumed alcohol, so alcohol cannot be considered a risk factor for ESCC 3 -Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk 24
Opium consumption	--------------	-Case control107, 24 - Cohort 25	------------------	- OR=2.12; 95% CI:1.21-3.7424 - Opium use was associated with a significantly increased risk of ESCC: AOR 1.77, 95% CI 1.17-2.68 107 - AHR for all mortality causes associated with use of opium was 1.86 (95% CI, 1.68 - 2.06)25
PAH exposure	-Review17	-Case control 36 -Cross sectional35	- Intakes are thought to be relatively high in Europe, although measures are only available from a few, generally high-income countries.17	- BaP daily intake in controls: high-risk area (Golestan)>lowrisk area (91.4 vs. 70.6 ng/day, p<0.01) 36 -41% of people in Golestan (1- OHPG)>5 pmol/mL (very high exposure) 35
Fungus contamination of foods	-Cross sectional (ecological study)38	-Cross sectional (ecologic study) 40 -Cross sectional (ecologic study)41	FB1 and FB2 levels were significantly higher in high risk area (p=0.01)38	-FB1-contaminated rice: High-risk area (75%)>low risk (21.4%) (p=0.02) 40 -AF level of wheat flour: Total AF and AFB1 were significantly higher in samples obtained from high risk area 41
Oral and dental hygiene	Population based Case control study 29	Population-based Case control study 45, 46	-Rarely visited a dentist in ESCC cases: OR=1.8 for white people OR =1.7 for black people -Rarely visited a dentist at or below the poverty level: OR=2.6 for white people OR=4.2 for black people 29	- Poor oral hygiene in ESCC: OR=2.3745 -Poor oral hygiene with gastric atrophy elevated ESCC risk: OR=8.6546
HPV	- Review10 - Pooled from six case control studies 52	-Cross sectional50 -Case control51	HPV in ESCC: 1- United States: 3%, - High risk areas in Asia (Japan, China, Hong Kong, India, Pakistan, and Korea), South Africa, Alaska, and Australia: 13- 63% ( overall 22%.)10 2- South Africa, Australia, Central and Eastern Europe, Brazil, Iran, and China: -E6 antibody: HPV16: OR=1.89 HPV6: OR=2.53 52	1- HPV in ESCC: - men: 52.8% -women : 43.7% positive cases HPV-16: 54.7%50 2- No significant difference between cancerous and noncancerous 51
Low level of vitamin A&C intake	-Systematic review59	-Cross sectional in healthy participants in Golestan 44	- A decreased risk associated with high retinol and β-carotene intake (combined OR=0.66, 95% CI:0.54- 0.81) 59	-Severe deficiency in vitamin intake among women and rural dwellers in Golestan: Daily intake (rural women) < LTI (lowest threshold intakes): vitamin A: 67% (p< 0.01) vitamin C : 73% 44
High temperature cooking and frying (dietary intake of heterocyclic amines)	Population-based Case control study	Case control	Heterocyclic amine intake might be associated with an increase in risk of ESCC (50-70% increased risk)	-Frying index: p<0.01 ESCC cases:18.2:1 High risk controls: 12.8:1 Low risk controls: 2.6:1 -Cooking oil reuse: p<0.05 ESCC cases: 37.5% High risk controls: 25% Low risk controls: 7.5%
Hot beverage consumption	---------------	Case control	---------------	Risk compared to warm : -hot black tea (OR: 2.07) -very hot black tea (OR:8.16)

SES: socioeconomic status, AOR: adjusted odds ratio, OR: odds ratio, ESCC: Esophageal squamous cell carcinoma, AHR: djusted Hazard Ratio, PAH: polycyclic aromatic hydrocarbons, BaP: benzo(a)pyrene, FB1 and FB2: fumonisin B1& B2, P: P.value, HPV: Human papilloma virus, CI: confidence interval