CRC arises from adenomatous and serrated colon polyps that are identifiable with colonoscopy. Several studies have reported an association between microbiota composition in feces or colonic mucosa, and CRC. These studies were generally small and did not control for host genotype or early childhood exposures, the two most influential factors in setting the gut microbiota. We propose to determine the association between the gut microbiota and colon polyps by comparing microbiota diversity and taxa in 45 monozygotic (MZ) twin pairs discordant for a history of colon polyps. Using polyp-discordant MZ twins as subjects is an advantage because both early childhood environment and genetic factors are controlled. Twins recruited from the California Twin Program will collect and return stool samples in specimen tubes that we provide, along with a diet questionnaire, lifestyle and exposure questionnaire, a signed HIPAA form to allow collection of medical records verifying the polyps and colonoscopy, and a signed informed consent, by mail. Based on a previous study of microbiota in lymphoma-discordant twins, we expect a 70% compliance rate. Microbiota diversity and taxa will be determined using 16rs sequencing of 150 mg of stool in the laboratory of Dr. Jacques Ravel, an international microbiome expert at the University of Maryland's Institute for Genome Sciences. Dr. Ravel's team will perform the DNA sequencing assays and bioinformatics and provide microbiota measures of diversity (Shannon's index as a measure of within person differences or alpha diversity, and Unifrac to measure between-person differences, or beta diversity). Taxonomic classification to the species level will be performed using QIIME and other standard software. We will use a conditional logistic regression framework to investigate the difference in gut microbiome diversity and specific bacterial species between MZ twins with and without colon polyps. The minimum detectable odds ratio for a 1 unit increase (i.e. a 1 SD increase in the biomarker) is 1.86 ( = 0.05) and 2.48 ( = 0.002), which is similar to the microbiota differences observed in our pilot study of 13 lymphoma-discordant pairs (mean differences extrapolated to an OR). The significance of this pilot study lies in the potential to demonstrate a relationship between the gut microbiota and colon polyps independent of host genotype or early childhood exposures.
Colorectal cancer (CRC) has a huge public health impact in the U.S, with over 140,000 new diagnoses and 50,000 deaths estimated in 2011 (SEER.cancer.gov). CRC arises from adenomatous and serrated colon polyps that are identifiable with colonoscopy. The composition of the gut microbiome is thought to play a role in maintaining normal immunity and protecting the colon from damage that could lead to polyps, and then CRC. We propose to identify bacteria associated with colon polyps in order to further understand colon polyp development. As the U.S. population ages, colonoscopy and CRC will increasingly become a challenge and burden. This study could provide additional information useful for colonoscopy risk stratification and even prevention, with non-invasive interventions such as probiotics.
