Abstract
Colorectal cancer (CRC) is a major public health issue, and there are limited studies on the association between 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) polymorphism and CRC. We used two national databases from Taiwan to examine whether HSD17B4 rs721673, rs721675, and alcohol intake were independently and interactively correlated with CRC development. We linked the Taiwan Biobank (TWB) participants' health and lifestyle information and genotypic data from 2012 to 2018 to the National Health Insurance Database (NHIRD) to confirm their medical records. We performed a genome-wide association study (GWAS) using data from 145 new incident CRC cases and matched 1316 healthy, non-CRC individuals. We calculated the odds ratios (OR) and 95% confidence intervals (CI) for CRC based on multiple logistic regression analyses. HSD17B4 rs721673 and rs721675 on chromosome 5 were significantly and positively correlated with CRC (rs721673 A > G, aOR = 2.62, p = 2.90 × 10(-8); rs721675 A > T, aOR = 2.61, p = 1.01 × 10(-6)). Within the high-risk genotypes, significantly higher ORs were observed among the alcohol intake group. Our results demonstrated that the rs721673 and rs721675 risk genotypes of HSD17B4 might increase the risk of CRC development in Taiwanese adults, especially those with alcohol consumption habits.