Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on clinical outcomes of colorectal cancer (CRC) are not defined. This study aimed to evaluate the association between metformin use and mortality of CRC in diabetic patients. We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin. Patient's demographics, clinical characteristics, overall mortality and CRC‐specific mortality were analyzed. After a median follow‐up of 41 months, there were 71 total deaths (27.5%) and 55 CRC‐specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC‐specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (p = 0.018) and CRC‐specific mortality (p = 0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 0.66; 95% CI 0.476–0.923; p = 0.015) and CRC‐specific mortality (HR, 0.66; 95% CI 0.45–0.975; p = 0.037) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC‐specific and overall mortality.

Objective: Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. Methods: We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. Results: We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10⁻¹⁴), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10⁻¹⁰) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10⁻⁹), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10⁻¹²) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10⁻⁵)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. Conclusions: Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.