Predictors of circulating tumor-derived methylated BCAT1 and IKZF1 DNA in colorectal cancer patients.
567 Background: Blood tests detecting circulating tumor-derived DNA (ctDNA) are being developed for colorectal cancer (CRC) screening and monitoring. However, the underlying tumor biology resulting in circulating DNA is not well understood. This study aimed to elucidate tumor features associated with methylated BCAT1 and IKZF1 DNA in blood as well as patient demographics that predict biomarker appearance. Methods: 129 people with invasive CRC had blood collected prior to surgery. Patient sociodemographic factors were recorded. Extracted circulating cell-free DNA was assayed for methylated BCAT1 and IKZF1. Patient factors and tumor features including location, size, depth of invasion (T stage), degree of differentiation, vascularity, lymphatic and perineurial invasion, lymph node involvement and presence of metastasis were compared with blood test results using multivariate logistic regression analysis. Results: The distribution of CRC stages I to IV were 34, 43, 41 and 11, respectively and 72 (56%) were blood positive for methylated BCAT1/IKZF1. Positivity was associated with distally located tumors and a higher T stage (Table). Gender, age, BMI, race, smoking and medications were not associated with blood positivity rates, but increased alcohol intake ( > 7 drinks/week, n = 31) was associated (OR 5.7, 95% CI 1.1-28.7, p = 0.036). Conclusions: The strongest predictor for appearance of ctDNA was invasion depth of the tumor. Demographic features did not influence the positivity rate of the BCAT1/ IKZF1 CRC blood test, strengthening the validity of this blood test for CRC screening and monitoring in the general population. [Table: see text]