AIM: To explore the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the α-tocopherol, β-carotene cancer prevention study. METHODS: About 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression. RESULTS: We found that methylation changes of 31 CpG sites were associated with CRC risk at P < 0.01 level. Though none of these 31 sites remained statistically significant after Bonferroni correction, the most statistically significant CpG site associated with CRC risk achieved a P value of 1.0 × 10(-4). The CpG site is located in DSP gene, and the risk estimate was 1.52 (95% CI: 0.91-2.53) and 2.62 (95% CI: 1.65-4.17) for the second and third tertile comparing with the lowest tertile respectively. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression. CONCLUSION: The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.
AIM: To explore the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the α-tocopherol, β-carotene cancer prevention study. METHODS: About 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression. RESULTS: We found that methylation changes of 31 CpG sites were associated with CRC risk at P < 0.01 level. Though none of these 31 sites remained statistically significant after Bonferroni correction, the most statistically significant CpG site associated with CRC risk achieved a P value of 1.0 × 10(-4). The CpG site is located in DSP gene, and the risk estimate was 1.52 (95% CI: 0.91-2.53) and 2.62 (95% CI: 1.65-4.17) for the second and third tertile comparing with the lowest tertile respectively. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression. CONCLUSION: The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.
Entities:
Keywords:
Colorectal cancer; DNA methylation; Susceptibility
Authors: Eddy H J van Roon; Marjo van Puijenbroek; Anneke Middeldorp; Ronald van Eijk; Emile J de Meijer; Dianhdra Erasmus; Kim A D Wouters; Manon van Engeland; Jan Oosting; Frederik J Hes; Carli M J Tops; Tom van Wezel; Judith M Boer; Hans Morreau Journal: BMC Cancer Date: 2010-05-05 Impact factor: 4.430
Authors: Eloisi C Lopes; Ester Valls; Maria E Figueroa; Alexander Mazur; Fan-Guo Meng; Gabriela Chiosis; Peter W Laird; Nicole Schreiber-Agus; John M Greally; Egor Prokhortchouk; Ari Melnick Journal: Cancer Res Date: 2008-09-15 Impact factor: 12.701
Authors: Dominique J P M Stumpel; Pauline Schneider; Eddy H J van Roon; Judith M Boer; Paola de Lorenzo; Maria G Valsecchi; Renee X de Menezes; Rob Pieters; Ronald W Stam Journal: Blood Date: 2009-10-23 Impact factor: 22.113
Authors: Rudolf Kaaks; Pär Stattin; Stéphanie Villar; Anna R Poetsch; Laure Dossus; Alexandra Nieters; Elio Riboli; Richard Palmqvist; Göran Hallmans; Christoph Plass; Marlin D Friesen Journal: Cancer Res Date: 2009-06-23 Impact factor: 12.701
Authors: Brock C Christensen; E Andres Houseman; Carmen J Marsit; Shichun Zheng; Margaret R Wrensch; Joseph L Wiemels; Heather H Nelson; Margaret R Karagas; James F Padbury; Raphael Bueno; David J Sugarbaker; Ru-Fang Yeh; John K Wiencke; Karl T Kelsey Journal: PLoS Genet Date: 2009-08-14 Impact factor: 5.917
Authors: Andrew E Teschendorff; Usha Menon; Aleksandra Gentry-Maharaj; Susan J Ramus; Simon A Gayther; Sophia Apostolidou; Allison Jones; Matthias Lechner; Stephan Beck; Ian J Jacobs; Martin Widschwendter Journal: PLoS One Date: 2009-12-18 Impact factor: 3.240
Authors: M Alexander; J B Burch; S E Steck; C-F Chen; T G Hurley; P Cavicchia; N Shivappa; J Guess; H Zhang; S D Youngstedt; K E Creek; S Lloyd; K Jones; J R Hébert Journal: Int J Colorectal Dis Date: 2016-10-22 Impact factor: 2.571
Authors: Dragan Milenkovic; Wim Vanden Berghe; Céline Boby; Christine Leroux; Ken Declerck; Katarzyna Szarc vel Szic; Karen Heyninck; Kris Laukens; Martin Bizet; Matthieu Defrance; Sarah Dedeurwaerder; Emilie Calonne; Francois Fuks; Guy Haegeman; Guido R M M Haenen; Aalt Bast; Antje R Weseler Journal: PLoS One Date: 2014-04-24 Impact factor: 3.240
Authors: Shuji Ogino; Paul Lochhead; Andrew T Chan; Reiko Nishihara; Eunyoung Cho; Brian M Wolpin; Jeffrey A Meyerhardt; Alexander Meissner; Eva S Schernhammer; Charles S Fuchs; Edward Giovannucci Journal: Mod Pathol Date: 2013-01-11 Impact factor: 7.842