Risk factors for esophageal iodine‐unstained lesions and changing trends among Japanese alcohol‐dependent men (2003‐2018)

Globally, a decreasing incidence of male esophageal squamous cell carcinoma (ESCC) has been observed in recent decades. We evaluated the determinants of esophageal distinct iodine‐unstained lesions (DIULs), high‐cancer‐risk lesions and ESCC, among 3858 Japanese alcohol‐dependent men (40‐79 years) who underwent chromoendoscopic screening between 2003 and 2018. The initial screening detected DIULs ≥ 5 mm in 541 patients (dysplasia in 319 and SCC in 129) and multiple DIULs in 640. The detection rates for DIULs and chronic atrophic gastritis (CAG), pack‐years, and the mean corpuscular volume (MCV) decreased over the course of the study period, while the detection of hiatal hernia and/or columnar‐lined esophagus (HH/CLE) and the carriers of inactive heterozygous aldehyde dehydrogenase‐2 (ALDH2, rs671) increased. Multiple logistic regression analyses showed that an older age, larger number of pack‐years, smaller body mass index, larger MCV, presence of a slow‐metabolizing alcohol dehydrogenase‐1B genotype (rs1229984), presence of an inactive heterozygous ALDH2 genotype, and more advanced degree of CAG increased the odds ratios (ORs) for DIULs, while the 2008‐2013 and 2014‐2018 screening periods had lower ORs for DIULs than the 2003‐2007 screening period. The presence of HH/CLE decreased the OR for multiple DIULs and was associated with a more proximal location of ESCC. In conclusion, the detection of DIULs in an alcohol‐dependent population decreased between 2003 and 2018. In addition to reported determinants of ESCC, CAG and HH/CLE were associated with the risk of DIULs. Enigmatically, however, the decline in the detection of DIULs was not adequately explained by these factors and warrants further research.