• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8455-8460
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• 2016

Background: Poor participation rates are often observed in colorectal cancer (CRC) screening programs utilising faecal occult blood tests. This may be from dislike of faecal sampling, or having benign bleeding conditions that can interfere with test results. These barriers may be circumvented by offering a blood-based DNA test for screening. The aim was to determine if program participation could be increased by offering a blood test following faecal immunochemical test (FIT) non-participation. Materials and Methods: People were invited into a CRC screening study through their General Practice and randomised into control or intervention (n=600/group). Both groups were mailed a FIT (matching conventional screening programs). Participation was defined as FIT completion within 12wk. Intervention group non-participants were offered a screening blood test (methylated BCAT1/IKZF1). Overall participation was compared between the groups. Results: After 12wk, FIT participation was 82% and 81% in the control and intervention groups. In the intervention 96 FIT nonparticipants were offered the blood test - 22 completed this test and 19 completed the FIT instead. Total screening in the intervention group was greater than the control (88% vs 82%, p<0.01). Of 12 invitees who indicated that FIT was inappropriate for them (mainly due to bleeding conditions), 10 completed the blood test (83%). Conclusions: Offering a blood test to FIT non-participants increased overall screening participation compared to a conventional FIT program. Blood test participation was particularly high in invitees who considered FIT to be inappropriate for them. A blood test may be a useful adjunct test within a FIT program.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.126-132
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• 2019

Background: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. Methods: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in ${\beta}$ value above 0.1 for three consecutive years. Results: We found three significant CpG sites with differentially methylated ${\beta}$ values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated ${\beta}$ values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). Conclusion: This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.77-82
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• 1998

In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.

• BMB Reports
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• v.55 no.11
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• pp.553-558
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• 2022

Hepatocellular carcinoma (HCC) is dangerous cancer that often evades early detection because it is asymptomatic and an effective detection method is lacking. For people with chronic liver inflammation who are at high risk of developing HCC, a sensitive detection method for HCC is needed. In a meta-analysis of The Cancer Genome Atlas pan-cancer methylation database, we identified a CpG island in the USP44 promoter that is methylated specifically in HCC. We developed methylation-sensitive high-resolution melting (MS-HRM) analysis to measure the methylation levels of the USP promoter in cell-free DNA isolated from patients. Our MS-HRM assay correctly identified 40% of patients with early-stage HCC, whereas the α-fetoprotein test, which is currently used to detect HCC, correctly identified only 25% of early-stage HCC patients. These results demonstrate that USP44 MS-HRM analysis is suitable for HCC surveillance.

• Journal of Genetic Medicine
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• v.14 no.1
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• pp.18-22
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• 2017

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.133-137
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• 2010

Purpose: Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome caused by a methylation abnormality at chromosome 11p15, consisting of two imprinting centers, BWSIC1 (IGF2, H19) and BWSIC2 (LIT1, KvDMR). This study evaluated the applicability of a methylation-specific (MS) PCR RFLP method for the genetic diagnosis of BWS. Materials and Methods: A total of 12 patients were recruited based on clinical findings. Karyotyping was performed using peripheral blood leukocytes, and genomic DNA was treated with bisulfate and amplified using methylation-specific primers. RFLP was conducted with restriction enzymes in differentially methylated regions of LIT1, H19, and IGF2. Results: The 12 BWS patients had normal karyotypes. Abnormal methylation patterns in the BWSIC2 (LIT1) region were identified in seven patients (58.3%) using the MS-PCR RFLP method. Conclusions: The MS-PCR RFLP method is a simple, economical genetic test. It detected genetic abnormalities in 50-60% of BWS patients, suggesting that it can be used as a screening test. A more precise method is required, however, to enhance the detection rate of genetic abnormalities, especially in BWSIC1 region.