Study participants and study design

This study recruited consecutive patients who went to the outpatient clinic of the Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China with a digestive system complaint. These patients were recommended to undergo a colonoscopy between May 2006 and October 2010. All of them were without a history of regular folate intake, former resection or a diagnosis of CRA, polyposis syndrome, inflammatory bowel disease and other risk factors for CRA. The initial data from patients found to have an adenoma at baseline were matched for age, sex, residential location (urban or rural), educational history, and economic history to those without a baseline adenoma in order to reduce the effect of bias as much as possible on the demographic and clinical characteristics. All study participants underwent a complete colonoscopy as described below, during which all identified adenomatous polyps were removed and biopsied. Blood samples for serum folate were collected before the colonoscopy was undertaken. Colonoscopy and pathology results enabled a diagnosis of CRA or A-CRA.

A control study was carried out at baseline to observe the relationship between serum folate levels and the presence of CRA or A-CRA. Then, cohort study was carried out to determine any change of CRA and A-CRA occurrence and recurrence after follow-up in participants with a normal baseline colonoscopy and in patients with diagnosed CRA who were randomly selected using a computer-generated randomization schedule based on prospective observations. The selected study participants were then asked to complete a questionnaire concerning related confounders. Conditional logistic regression was used to eliminate confounders and to investigate factors that were independently associated with CRA. Follow-up started from the first colonoscopy or polypectomy.

The study protocol was approved by the Institutional Review Board of Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai, China. All 1310 study participants were provided written informed consent.