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DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids.
Dig Dis Sci. 2011 Feb; 56(2):387-96.DD

Abstract

BACKGROUND

DNA methylation varies throughout the normal colorectal mucosa and DNA methylation in normal appearing mucosa is associated with serrated and adenomatous neoplasia elsewhere within the colorectum.

AIMS

The purpose of this study was to measure luminal chemistry, rectal proliferation and mucosal DNA methylation and thus determine whether regional and pathological patterns of DNA methylation could be explained by luminal and epithelial factors.

METHODS

Twenty healthy subjects had normal rectal mucosal biopsies and a 24-h fecal collection. Rectal biopsies were analyzed for epithelial proliferation (Ki67 immunohistochemistry) and DNA methylation at 17 different markers, including "type A" markers (ESR1, GATA5, HIC1, HPP1, SFRP1), "type C" markers (MGMT, MLH1, CDKN2A, MINT1, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. Fecal analysis included short-chain fatty acids (SCFA), pH and ammonia. Mean "type A" and CIMP panel methylation Z-scores were calculated.

RESULTS

Rectal proliferation was significantly correlated with methylation at ESR1 (ρ = 0.81, P = 0.003) and GATA5 (ρ = 0.78, P = 0.012). LINE-1 methylation was 71.7 vs. 74.1%, in patients with "low" and "high" fecal total SCFA concentration (defined by the median value), respectively (P = 0.0019). On multivariate linear regression "type A" methylation was independently associated with rectal proliferation (P = 0.001). LINE-1 methylation was directly associated with rectal proliferation (P = 0.038) and total fecal SCFA concentration (P = 0.002), and inversely associated with fecal NH(3) concentrations (P = 0.003).

CONCLUSIONS

DNA methylation in normal rectal mucosa is associated with crypt proliferation and fecal SCFA concentration. These associations may help to explain regional differences in DNA methylation as well as providing a possible link between the colorectal lumen and carcinogenesis.

Links

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Authors+Show Affiliations

Worthley DL
Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia. daniel.worthley@uqconnect.edu.au
Whitehall VL
No affiliation info available
Le Leu RK
No affiliation info available
Irahara N
No affiliation info available
Buttenshaw RL
No affiliation info available
Mallitt KA
No affiliation info available
Greco SA
No affiliation info available
Ramsnes I
No affiliation info available
Winter J
No affiliation info available
Hu Y
No affiliation info available
Ogino S
No affiliation info available
Young GP
No affiliation info available
Leggett BA
No affiliation info available

MeSH

Aberrant Crypt FociAdultAgedAmmoniaBiomarkersColorectal NeoplasmsDNA MethylationFatty Acids, VolatileFecesFemaleHumansIntestinal MucosaMaleMiddle AgedRectum

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20635146

Citation

Worthley, Daniel L., et al. "DNA Methylation in the Rectal Mucosa Is Associated With Crypt Proliferation and Fecal Short-chain Fatty Acids." Digestive Diseases and Sciences, vol. 56, no. 2, 2011, pp. 387-96.
Worthley DL, Whitehall VL, Le Leu RK, et al. DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids. Dig Dis Sci. 2011;56(2):387-96.
Worthley, D. L., Whitehall, V. L., Le Leu, R. K., Irahara, N., Buttenshaw, R. L., Mallitt, K. A., Greco, S. A., Ramsnes, I., Winter, J., Hu, Y., Ogino, S., Young, G. P., & Leggett, B. A. (2011). DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids. Digestive Diseases and Sciences, 56(2), 387-96. https://doi.org/10.1007/s10620-010-1312-4
Worthley DL, et al. DNA Methylation in the Rectal Mucosa Is Associated With Crypt Proliferation and Fecal Short-chain Fatty Acids. Dig Dis Sci. 2011;56(2):387-96. PubMed PMID: 20635146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids. AU - Worthley,Daniel L, AU - Whitehall,Vicki L J, AU - Le Leu,Richard K, AU - Irahara,Natsumi, AU - Buttenshaw,Ronald L, AU - Mallitt,Kylie-Ann, AU - Greco,Sonia A, AU - Ramsnes,Ingunn, AU - Winter,Jean, AU - Hu,Ying, AU - Ogino,Shuji, AU - Young,Graeme P, AU - Leggett,Barbara A, Y1 - 2010/07/16/ PY - 2010/03/11/received PY - 2010/06/14/accepted PY - 2010/7/17/entrez PY - 2010/7/17/pubmed PY - 2011/3/12/medline SP - 387 EP - 96 JF - Digestive diseases and sciences JO - Dig Dis Sci VL - 56 IS - 2 N2 - BACKGROUND: DNA methylation varies throughout the normal colorectal mucosa and DNA methylation in normal appearing mucosa is associated with serrated and adenomatous neoplasia elsewhere within the colorectum. AIMS: The purpose of this study was to measure luminal chemistry, rectal proliferation and mucosal DNA methylation and thus determine whether regional and pathological patterns of DNA methylation could be explained by luminal and epithelial factors. METHODS: Twenty healthy subjects had normal rectal mucosal biopsies and a 24-h fecal collection. Rectal biopsies were analyzed for epithelial proliferation (Ki67 immunohistochemistry) and DNA methylation at 17 different markers, including "type A" markers (ESR1, GATA5, HIC1, HPP1, SFRP1), "type C" markers (MGMT, MLH1, CDKN2A, MINT1, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. Fecal analysis included short-chain fatty acids (SCFA), pH and ammonia. Mean "type A" and CIMP panel methylation Z-scores were calculated. RESULTS: Rectal proliferation was significantly correlated with methylation at ESR1 (ρ = 0.81, P = 0.003) and GATA5 (ρ = 0.78, P = 0.012). LINE-1 methylation was 71.7 vs. 74.1%, in patients with "low" and "high" fecal total SCFA concentration (defined by the median value), respectively (P = 0.0019). On multivariate linear regression "type A" methylation was independently associated with rectal proliferation (P = 0.001). LINE-1 methylation was directly associated with rectal proliferation (P = 0.038) and total fecal SCFA concentration (P = 0.002), and inversely associated with fecal NH(3) concentrations (P = 0.003). CONCLUSIONS: DNA methylation in normal rectal mucosa is associated with crypt proliferation and fecal SCFA concentration. These associations may help to explain regional differences in DNA methylation as well as providing a possible link between the colorectal lumen and carcinogenesis. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/20635146/DNA_methylation_in_the_rectal_mucosa_is_associated_with_crypt_proliferation_and_fecal_short_chain_fatty_acids_ L2 - https://doi.org/10.1007/s10620-010-1312-4 DB - PRIME DP - Unbound Medicine ER -