To the Editor We read with great interest the systematic review and meta-analysis by Petrelli and colleagues published in JAMA Oncology.1 Among 1.5 million patients with colon cancer, those with left-sided tumors were shown to have better prognosis and lower risk of death in all stages compared with right-sided tumors. As the authors mention, different embryologic origin and poor histological and genetic features, including a higher rate of diploidy, mucinous histologic findings, microsatellite instability, CpG island methylation, and BRAF mutation in right-sided tumors, and more frequent p53 and KRAS mutations in left-sided tumors might explain the difference in prognosis, but the exact mechanism is not known.