Affiliations: [a] Cancer Research, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University of South Australia, Bedford Park, South Australia, Australia | [b] Clinical Genomics Pty Ltd, North Ryde, New South Wales, Australia | [c] Flinders Breast Cancer Unit, Flinders Medical Centre, Bedford Park, South Australia, Australia | [d] Urology Services, Flinders Medical Centre, Bedford Park, South Australia, Australia | [e] Bowel Health Service, Flinders Medical Centre, Bedford Park, South Australia, Australia
Correspondence:
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Corresponding author: Jean M. Winter, Level 3 Flinders Centre for Innovation in Cancer, Flinders Drive, Bedford Park, South Australia 5042, Australia. Tel.: +61 8 8275 1075; E-mail: [email protected].
Abstract: BACKGROUND: Detection of circulating cell-free DNA (ccfDNA) methylated in BCAT1 and IKZF1 is sensitive for detection of colorectal cancer (CRC), but it is not known if these biomarkers are present in other common adenocarcinomas. OBJECTIVE: Compare methylation levels of BCAT1 and IKZF1 in tissue and plasma from breast, prostate, and colorectal cancer patients. METHODS: Blood was collected from 290 CRC, 32 breast and 101 prostate cancer patients, and 606 cancer-free controls. Tumor and matched normal tissues were collected at surgery: 26 breast, 9 prostate and 15 CRC. DNA methylation in BCAT1 and IKZF1 was measured in blood and tissues. RESULTS: Either biomarker was detected in blood from 175/290 (60.3%) of CRC patients. The detection rate was higher than that measured in controls (48/606 (8.1%), OR = 18.2, 95%CI: 11.1–29.0). The test positivity rates in breast and prostate cancer patients were 9.4% (3/32) and 6.9% (7/101), respectively, and not significantly different to that measured in gender-matched controls (8.0% (33/382) females (OR = 0.84, 95%CI: 0.23–3.1) and 7.6% (26/318) males (OR = 0.86, 95%CI: 0.65–2.1). In tumor and non-neoplastic tissues, 93.5% (14/15) of CRC tumors were methylated in BCAT1 and/or IKZF1 (p< 0.004). Only 11.5% (3/26) and 44.4% (4/9) (p= 0.083) of breast and prostate tumors were hypermethylated in these two genes. CONCLUSIONS: Detection of circulating DNA methylated in BCAT1 and IKZF1 is sensitive and specific for CRC but not breast or prostate cancer.
