Background:Colorectal cancer(CRC)is the third-most-common malignancy and the second-leading cause of cancer-related deaths worldwide and current screening methods such as guaiac-based fecal occult blood test(gFOBT),fe...Background:Colorectal cancer(CRC)is the third-most-common malignancy and the second-leading cause of cancer-related deaths worldwide and current screening methods such as guaiac-based fecal occult blood test(gFOBT),fecal immunochemical test(FIT),and colonoscopy have their own pros and cons.This study aimed to assess the effectiveness of a fecal DNA methylation test by using methylated SDC2(mSDC2)as the epigenetic biomarker for detecting CRC in a screening-naïve population.Methods:Fecal mSDC2 test and FIT were simultaneously performed on eligible 40-to 74-year-old adults of a regional township in China.Subjects with positive results were recommended for colonoscopy.Data of positivity rates,positive predicted values(PPVs),and detection rates associated with clinical characteristics were analysed.Results:The positivity rate of mSDC2 was 7.6%for 10,578 participants with valid results from both fecal mSDC2 test and FIT.With an adherence rate of 63.8%to colonoscopy referral,25 CRCs,189 advanced adenomas(AAs),and 165 non-advanced adenomas(NAAs)and polyps were detected.The PPVs of mSDC2 were 4.93%,37.28%,and 32.54%for CRC,AA,and non-advanced lesions,respectively.When the CRCs and AAs were counted as positive findings,the fecal mSDC2 test showed a higher detective rate than FIT(relative risk[RR],1.313[1.129-1.528],P<0.001).When NAAs and polyps were also specified as treatable lesions,the mSDC2 test was more effective in detecting these benign growths(RR,1.872[1.419-2.410];P<0.001).A combination of mSDC2 and FIT detected 29 CRCs,298 AAs,and 234 NAAs and polyps.Overall,the fecal mSDC2 test had a higher detection rate for both advanced and non-advanced colonic lesions.The false-positive rate of the fecal mSDC2 test was comparable to that of FIT(RR,1.169[0.974-1.403];P=0.113).Conclusions:The single-target stool-based mSDC2 test can effectively and accurately detect CRC and precancerous lesions in a large-scale CRC-screening program.Trial registration number:NCT05374369.展开更多
基金supported by the National Key Research and Development Program of China[2017YFC1308800 to H.Z.]and the Talent Project of Innovation and Entrepreneurship in Developmental Zone of Guangzhou[Grant No.2017-L1772022-L025 to H.Z.].
文摘Background:Colorectal cancer(CRC)is the third-most-common malignancy and the second-leading cause of cancer-related deaths worldwide and current screening methods such as guaiac-based fecal occult blood test(gFOBT),fecal immunochemical test(FIT),and colonoscopy have their own pros and cons.This study aimed to assess the effectiveness of a fecal DNA methylation test by using methylated SDC2(mSDC2)as the epigenetic biomarker for detecting CRC in a screening-naïve population.Methods:Fecal mSDC2 test and FIT were simultaneously performed on eligible 40-to 74-year-old adults of a regional township in China.Subjects with positive results were recommended for colonoscopy.Data of positivity rates,positive predicted values(PPVs),and detection rates associated with clinical characteristics were analysed.Results:The positivity rate of mSDC2 was 7.6%for 10,578 participants with valid results from both fecal mSDC2 test and FIT.With an adherence rate of 63.8%to colonoscopy referral,25 CRCs,189 advanced adenomas(AAs),and 165 non-advanced adenomas(NAAs)and polyps were detected.The PPVs of mSDC2 were 4.93%,37.28%,and 32.54%for CRC,AA,and non-advanced lesions,respectively.When the CRCs and AAs were counted as positive findings,the fecal mSDC2 test showed a higher detective rate than FIT(relative risk[RR],1.313[1.129-1.528],P<0.001).When NAAs and polyps were also specified as treatable lesions,the mSDC2 test was more effective in detecting these benign growths(RR,1.872[1.419-2.410];P<0.001).A combination of mSDC2 and FIT detected 29 CRCs,298 AAs,and 234 NAAs and polyps.Overall,the fecal mSDC2 test had a higher detection rate for both advanced and non-advanced colonic lesions.The false-positive rate of the fecal mSDC2 test was comparable to that of FIT(RR,1.169[0.974-1.403];P=0.113).Conclusions:The single-target stool-based mSDC2 test can effectively and accurately detect CRC and precancerous lesions in a large-scale CRC-screening program.Trial registration number:NCT05374369.
