Abstract
Existing evidence remains inconclusive as to how the association between inactive ALDH2 and esophageal cancer (EC) depends on alcohol consumption. The study is based on the China Kadoorie Biobank cohort, with 10 years follow‐up of 0.5 million adults aged 30–79 years. ALDH2 activity was assessed by both self‐reported flushing response and Glu504Lys (rs671 G > A) polymorphism. Among both male and female participants who consumed alcohol less than weekly (n = 69,519; 211 EC cases), low active or inactive ALDH2 was not associated with increased EC risk [HRs (95% CIs): GA vs. GG 0.75 (0.54, 1.04); AA vs. GG 1.01 (0.46, 2.20)]. Among male weekly alcohol consumers, both flushing response [n = 59,380; 501 EC cases; HRs (95% CIs): “soon after drinking” vs. “no” flushing response 1.45 (1.05, 2.01)] and rs671 [n = 10,692; 94 EC cases; GA vs. GG 3.31 (1.94, 5.67)] were associated with EC risk. The increased EC risk associated with “soon” response or rs671 GA was apparent in men consuming alcohol ≥30g/d. Among male daily consumers, the HRs (95% CIs) for EC associated with 15g/d of alcohol were 1.28 (1.15, 1.44) for “soon” response [vs. other responses: 1.12 (1.09, 1.15); p interaction = 0.047; n = 36,401, 425 EC cases] and 1.41 (1.08, 1.82) for rs671 GA [vs. GG: 1.16 (1.06, 1.27); p interaction = 0.493; n = 6,607, 80 EC cases]. Self‐reported flushing response had low sensitivity (56.8%) and high specificity (88.4%) in identifying rs671 A allele among male weekly alcohol consumers. In conclusion, low‐activity ALDH2 was associated with increased EC risk among male heavy alcohol consumers. More accurate measurement of alcohol‐related EC risk allows better achievement of precision prevention.
Highlights
Esophageal cancer (EC) remains a global concern because of its increasing incidence and persistently poor survival.[1,2] China is among the highest EC incidence countries.[2]
We further examined the effects of selfreported flushing response, acetaldehyde dehydrogenase 2 (ALDH2) genotype and their joint effects with alcohol consumption on EC risk in male participants
We examined whether the association of EC risk with self-reported flushing response or ALDH2 genotype differed by the amount of alcohol consumed per day, and whether the association of EC risk with alcohol consumption differed by the flushing response or ALDH2 genotype, by using likelihood ratio test comparing models with and without cross-product term
Summary
Esophageal cancer (EC) remains a global concern because of its increasing incidence and persistently poor survival.[1,2] China is among the highest EC incidence countries.[2]. The ALDH2 Lys variant causes the well-known Asian flush, an unpleasant physiological response to alcohol consumption that includes facial flushing, nausea and tachycardia and inhibits alcohol consumption.[9]
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