Disease burden of oesophageal cancer attributable to genetic variants and alcohol consumption in Hong Kong, China

Background: Previous studies have identified a gene-environment interaction between the ALDH2*2 allele and alcohol consumption, but there is limited information on their contributions to disease burden in the general population, particularly in East Asia. We aim to assess the population-based disease burden of oesophageal cancer considering genetic variants and alcohol exposure in Hong Kong, China. Methods: We conducted random-effects meta-analyses to determine the pooled relative risk of oesophageal cancer for drinkers with the ALDH2*2 polymorphism in East Asia. We estimated the population attributable risk (PAR) for oesophageal cancers in Hong Kong, using the odds ratios (ORs) of alcohol consumption on oesophageal cancer for ALDH2*2 carriers, which were multiplied by age-sex-specific morbidity to compute estimates of attributable cases. Findings: Meta-analysis of 25 studies revealed that people with the ALDH2*2 polymorphism and higher level of alcohol exposure had a significantly greater risk of developing oesophageal cancer compared to individuals without the ALDH2*2 genotype who never consumed alcohol (no drinker: 1.21 [95% CI 0.97 – 1.52, light: 2.57 [1.92 – 3.44], moderate: 6.38 [4.21 – 9.67], and heavy: 36.00 [11.33 – 114.38]). In Hong Kong 2021, 34.6% [19.1-47.9] oesophageal cancer cases diagnosed were attributable to alcohol consumption, 19.2% [9.5-28.1] were attributable to ALDH2*2 polymorphism, while 44.1% [22.3-65.2] were attributable to the joint alcohol consumption and ALDH2*2 polymorphism. Males account for larger attributable disease burden due to alcohol and ALDH2*2 polymorphism (Male 49% vs Female 24%). Interpretation: This study implicates the importance of implementing a tailored oesophageal cancer screening program for individuals with the ALDH2*2 genotype in East Asia, emphasizing its importance for public health and policy. Despite limitations in relying on observational data, the study's strength lies in its comprehensive meta-analysis and regional population-based estimates, providing compelling evidence for the gene-environment interaction between the ALDH2*2 allele and alcohol consumption in relation to oesophageal cancer risk in East Asian populations. Funding: Health and Medical Research Fund (HMRF), Health Bureau, Government of Hong Kong SAR, China [20211791].