BACKGROUND: Some of colorectal cancers (CRCs) are familial, however, heterozygote relatives have approximately 80% lifetime risk of cancer. Risk assessment of CRC’s family could be calculated by direct measurement of mRNA gene expression and Bayesian theorem which is modifying initial background of pedigree risk with additional conditional information. This application has not been reported.METHODS: The cross-sectional translational sequential studies were performed: (1) adenomatous polyposis coli (APC) and MutS homolog (MSH)2 mRNA quantitative RT PCR gene expressions in tissue and whole blood CRC patients; (2) gene expression was determined in matched controls; and (3) pedigree and Bayesian analysis was calculated in the patient’s family of Proband.RESULTS: Fourty CRC and 31 control subjects were enrolled. The mean blood APC level control’s group was 13,261±670 fold-change (fc) and blood MSH2 level was 12,219±756 fc. The cut-off points for hereditary APC was 12,195 fc and MSH2 was 11,059 fc. The mean APC blood level in CRC subject was 11,578±2,638 fc and MSH2 blood level was 11,411±2,912 fc. There were significant differences APC and MSH level between tissue and blood level in CRC. Eight of 40 CRC subjects had a history of familial CRC. Four patients and 10 Probands were available for recurrence risk evaluation of pedigree analysis, RNA PCR quantitative and Bayesian calculation.CONCLUSION: There was determined a cut-off point of hereditary mRNA quantitative expression. The APC and MSH2 levels in CRC subjects were significantly lower than controls. Bayesian analysis allowed for the calculation of relative risk in CRC family members and considered in clinical practice.KEYWORDS: hereditary CRC, APC gene, MSH gene, Bayesian analysis
BACKGROUND
Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer (CRC), with heightened risk for younger population. Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria. However, those fail in term of applicability.
AIM
To determine a clear cut-off of
MSH2
gene expression for CRC heredity grouping factor. Further, the study also aims to examine the association of risk factors to the CRC heredity.
METHODS
The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through
MSH2
mRNA expression using reverse transcription-polymerase chain reaction and the disease’s risk factors. Data were analyzed through Chi-Square, Fischer exact, t-test, Mann-Whitney, and multiple logistics.
RESULTS
There are significant differences of
MSH2
within CRC group among tissue and blood; yet, negative for significance between groups. Through the blood gene expression fifth percentile, the hereditary CRC cut-off is 11059 fc, dividing the 40 CRC respondents to 32.5% with hereditary CRC. Significant risk factors include age, family history, and staging. Nonetheless, after multivariate control, age is just a confounder. Further, the study develops a probability equation with area under the curve 82.2%.
CONCLUSION
Numerous factors have significant relations to heredity of CRC patients. However, true important factors are staging and family history, while age and others are confounders. The study also established a definite cut-off point for heredity CRC based on mRNA
MSH2
expression, 11059 fc. These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.
Heterozygote relatives have approximately 80% lifetime colorectal cancer (CRC) risk. mRNA gene expression and Bayesian theorem can calculate CRC’s family risk through the initial pedigree proportion appended with conditional information. The study is the first to report such an application. The present cross-sectional and translational investigation tracked CRC patients’ tissue and blood measurement of adenomatous polyposis coli (APC) and MutS homolog (MSH)2 mRNA quantitative gene expressions, control matching, and ancestral analysis by pedigree and Bayesian theorem. Among 40 CRC patients, mean tissue level and hereditary cutoff of APC are 13,261 (670) fold-change (fc) and 12,195 fc, while 12,219 (756) fc and 11,059 fc for MSH2. A quarter of the CRC patients had a history of familial CRC. Meanwhile, four CRC patients and 10 probands were evaluated for recurrence risk via pedigree, quantitative PCR, and Bayesian analysis. We determined a cutoff point for hereditary mRNA quantitative expression. APC and MSH2 levels in the CRC subjects were significantly lower than controls. The Bayesian analysis builds ways to calculate relative risk in CRC patients’ family members and application in clinical practice.
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