Table 2. Major risk factors for esophageal cancer in Japan and China.

Risk factors	Information on strength of association
Japan
Cigarette smoking	Summary RR for ever smokers was 3.01 (95% CI: 2.30–3.94), based on 4 cohort and 11 case-control studies [Ref 19]
Alcohol drinking	Summary RR for ever drinkers was 3.30 (95% CI: 2.30–4.74), based on 9 cohort and 9 case-control studies [Ref 18]
Gastric atrophy	Positive associations observed in 3 clinical studies [Refs 42–44], but no prospective cohort studies confirmed these associations.
China
Low-incidence areasa
Cigarette smoking	RR was 2.06 (95% CI: 1.11–3.82) for those who smoked for ≥40 years in a cohort of Shanghai residents [Ref 32]
Alcohol drinking	RR was 2.02 (95% CI: 1.31–3.12) for regular drinkers in a cohort of Shanghai residents [Ref 32]
Drinking tea at high temperature	OR was 3.1 (95% CI: 2.2–4.3) in a case-control study in Jiangsu Province [Ref 33], but definitive evidence is lacking
High-incidence areasb,c
Cigarette smoking and alcohol drinking   (probable modest association)	RR was 1.32 (95% CI: 1.15–1.51) for current smokers and 1.12 (0.83–1.51) for currents smokers of ≥20 cigarettes per day [Ref 29] No significant association among those who consumed alcohol in the previous 12 months [Ref 29]
Family history	RR was 1.42 (95% CI: 1.29–1.56) for individuals with family history of esophageal cancer [Ref 67]
Nutritional deficiency	High intake of meat, eggs, and fresh fruit associated with decreased risk [Ref 29]
Food mutagens including nitrosamine   and its precursors	Ecologic studies showed that concentration of nitrate nitrogen was higher in high-incidence areas than in low-incidence areas [Refs 40, 41]

RR: relative risk; OR: odds ratio.

^aIn general, low-incidence areas are distributed in urban cities, including Beijing, Guangdong, Qidong county, Shanghai, and Zhongshan (Table 1).

^bHigh-incidence areas are defined as areas with an age-standardized rate >30 per 100 000 population, including rural areas such as Cixian and Changle (Table 1).

^cThe main findings in high-incidence areas are based on a prospective study of risk factors for esophageal and gastric cancers in the Linxian General Population Trial Cohort in China [Ref ²⁹].