Double-strand break damage and associated DNA repair genes predispose smokers to gene methylation.

Cancer Research
Shuguang LengSteven A Belinsky

Abstract

Gene promoter hypermethylation in sputum is a promising biomarker for predicting lung cancer. Identifying factors that predispose smokers to methylation of multiple gene promoters in the lung could affect strategies for early detection and chemoprevention. This study evaluated the hypothesis that double-strand break (DSB) repair capacity and sequence variation in genes in this pathway are associated with a high methylation index in a cohort of current and former cancer-free smokers. A 50% reduction in the mean level of DSB repair capacity was seen in lymphocytes from smokers with a high methylation index, defined as three or more of eight genes methylated in sputum, compared with smokers with no genes methylated. The classification accuracy for predicting risk for methylation was 88%. Single nucleotide polymorphisms within the MRE11A, CHEK2, XRCC3, DNA-PKc, and NBN DNA repair genes were highly associated with the methylation index. A 14.5-fold increased odds for high methylation was seen for persons with seven or more risk alleles of these genes. Promoter activity of the MRE11A gene that plays a critical role in recognition of DNA damage and activation of ataxia-telangiectasia mutated was reduced in persons with the risk allele...Continue Reading

References

Mar 15, 1989·International Journal of Cancer. Journal International Du Cancer·T C HsuC Furlong
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·S A BelinskyJ G Herman
Apr 27, 2001·Carcinogenesis·D H AuckleyS A Belinsky
Aug 20, 2003·International Journal of Cancer. Journal International Du Cancer·Hongbing ShenQingyi Wei
Dec 19, 2003·American Journal of Human Genetics·Christopher S CarlsonDeborah A Nickerson
Mar 18, 2004·Journal of the National Cancer Institute·Sholom WacholderNathaniel Rothman
Jul 29, 2004·DNA Repair·Oscar Fernandez-CapetilloAndré Nussenzweig
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Aug 18, 2004·Cancer Research·Li-E WangQingyi Wei
Sep 3, 2004·Nature Reviews. Cancer·Steven A Belinsky
Jan 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Pierre-Olivier EstèveSriharsa Pradhan
Jun 1, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Qing LanStephen Chanock
Jun 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Oliver MortusewiczHeinrich Leonhardt
Mar 4, 2006·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
May 19, 2006·American Journal of Epidemiology·Maurizio ManuguerraGiuseppe Matullo
Jun 17, 2006·Cancer Research·Xifeng WuGary E Swan
Jul 4, 2006·Journal of Medical Genetics·O KilpivaaraH Nevanlinna
Jul 13, 2006·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Clemens B TempferJohannes C Huber
Jul 18, 2006·Nucleic Acids Research·Lucía CondeJoaquín Dopazo
Nov 25, 2006·The Journal of Biological Chemistry·Pierre-Olivier EstèveSriharsa Pradhan
Dec 14, 2006·Human Molecular Genetics·Kristjana EinarsdóttirSara Wedrén
Jul 10, 2007·PLoS Genetics·Concetta CuozzoEnrico V Avvedimento

❮ Previous
Next ❯

Citations

Jan 26, 2010·Cancer Metastasis Reviews·Gerwin HellerSabine Zöchbauer-Müller
Jan 10, 2012·Antioxidants & Redox Signaling·Naveed Hussain
May 19, 2010·Carcinogenesis·Sungshim L ParkZuo-Feng Zhang
Mar 1, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shuguang LengSteven A Belinsky
Apr 19, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shuguang LengSteven A Belinsky
Dec 20, 2008·American Journal of Respiratory and Critical Care Medicine·Carla VerriUNKNOWN EUELC Consortium
Sep 17, 2013·American Journal of Respiratory and Critical Care Medicine·Shuguang LengSteven A Belinsky
Mar 7, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·A Jasmijn HubersErik Thunnissen
Oct 30, 2012·Journal of the National Cancer Institute·Yael Leitner-DaganTamar Paz-Elizur
Mar 15, 2016·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·A RosellJ Dorca
Jul 23, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Mathewos TessemaSteven A Belinsky
Jul 14, 2009·Mutation Research·Anthony P AlbinoZbigniew Darzynkiewicz
Aug 7, 2009·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Mar 13, 2014·International Journal of Cancer. Journal International Du Cancer·Josephine Mun Yee KoMaria Li Lung
Aug 29, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Gang DingZhaoheng Ding
Mar 31, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Laura OttiniFrancesca Marcon
Jun 23, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Justin A ColacinoLaura S Rozek
Aug 29, 2012·Biochemical and Biophysical Research Communications·Pierdonato BrunoSalvatore Mariotta
Feb 26, 2015·Journal of the National Cancer Institute·Shuguang LengSteven A Belinsky
Feb 14, 2018·American Journal of Respiratory and Critical Care Medicine·Shuguang LengSteven A Belinsky
Sep 15, 2017·Cancer Prevention Research·Steven A BelinskyDaniel D Karp
Aug 19, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Shuguang LengSteven A Belinsky
Feb 26, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Juan ChengYuxin Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.