Abstract B128: Change in use of folic acid-containing supplements after a diagnosis of colorectal cancer
Authors: Holmes Rebecca , Li Lin , Zheng Yingye , Potter John , Baron John , Le Marchand Loic , Stern Mariana , McKeown-Eyssen Gail , Newcomb Polly , Haile Robert , Limburg Paul , Ulrich Cornelia 
Published: May 2012

Abstract
B128

Background
The B vitamin folate affects colorectal carcinogenesis through effects on nucleotide synthesis and possibly DNA methylation. Animal models and epidemiologic evidence suggest that folate from diet and supplements can prevent the development of colorectal cancer (CRC), but that high folate intake after adenomas or cancer are established may accelerate progression or recurrence. The chemotherapeutic agent 5-fluorouracil inhibits thymidylate synthase, a folate-metabolizing enzyme, and the effect of folate intake on treatment efficacy is unknown. Supplement use and folate intake are high among adults in the U.S., particularly with food supply fortification, and higher still among cancer patients and survivors. However, few studies have addressed use of folic acid-containing supplements (FAS) among colorectal cancer patients, how use changes after diagnosis, and what factors determine changes in FAS use.

Methods
The Colon Cancer Family Registry (CCFR) is a multicenter study of colorectal cancer cases, their family members and controls, recruited since 1998 at six sites in the United States, Australia and Canada. The current analysis includes 1,092 CRC cases with epidemiologic data available from questionnaires administered at enrollment, asking about supplement use and other risk factors before diagnosis, and from follow-up questionnaires about 5 years later. Baseline characteristics for cases who began using FAS (including multivitamins) after diagnosis were compared to those for cases who used FAS neither before nor after diagnosis. We used logistic regression models to evaluate associations between age, sex, CCFR site, race, education, income, lifetime exercise, smoking, body mass index, and diet and change in FAS use, adjusting each model for age, sex and site, when appropriate.

Results
FAS use before CRC diagnosis was 35.4%, while 55.1% of cases used FAS after diagnosis. Women were more likely to begin FAS use after diagnosis (OR 1.60, 95% CI 1.17-2.19). Current smokers were less likely than nonsmokers to begin FAS use (OR 0.63, 95% CI 0.40-0.97), as were those consuming more red meat (OR 0.38, 95% CI 0.21-0.70 for those in the highest versus lowest intake categories, ptrend=0.012). Subjects with higher fruit intake were more likely to begin FAS use (OR 1.95, 95% CI 1.16-3.30 for highest versus lowest intake, ptrend=0.013). We also observed a suggestive association between lifetime physical activity and change in FAS use for active versus less active subjects (OR 1.48, 95% CI 1.01-2.16), though there was no trend with increasing levels of physical activity (ptrend=0.27). Finally, we found that residents of non-U.S. countries were less likely to begin FAS use (OR 0.57, 95% CI 0.33-0.96 for Ontario, Canada and OR 0.21, 95% CI 0.11-0.38 for Australia). Conclusions: Our analysis showed substantial increases in the use of folic acid-containing supplements after diagnosis with colorectal cancer in CCFR participants, especially among women, U.S. residents, nonsmokers, and those who consumed more fruit and less meat. This study begins to characterize CRC patients likely to be using FAS, and suggests that its use is widespread. This finding is notable given evidence that folate may accelerate progression of colorectal cancer, and the unknown effect that FAS intake may have on the efficacy of cancer treatment and on survival.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B128.