BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol exposures, although dietary factors, particularly folate, and human papillomavirus, are also risk factors. Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumor tissues, including HNSCC. This study aimed to determine whether global methylation in DNA derived from whole blood, a proxy tissue, is associated with HNSCC and to assess potential modification of this property by environmental or behavioral risk factors. METHODS: Global DNA methylation levels were assessed using a modified version of the combined bisulfite restriction analysis of the LRE1 sequence in a population-based case-control study of HNSCC from the Boston area. RESULTS: Hypomethylation lead to a significant 1.6-fold increased risk for disease (95% confidence interval, 1.1-2.4), in models controlled for other HNSCC risk factors. Smoking showed a significant differential effect (P < 0.03) on blood relative methylation between cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and low folate intake showed relationships with decreased global methylation, whereas in controls, antibody response to human papillomavirus 16 was associated with an increased global methylation level. DISCUSSION: DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol exposures, although dietary factors, particularly folate, and human papillomavirus, are also risk factors. Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumor tissues, including HNSCC. This study aimed to determine whether global methylation in DNA derived from whole blood, a proxy tissue, is associated with HNSCC and to assess potential modification of this property by environmental or behavioral risk factors. METHODS: Global DNA methylation levels were assessed using a modified version of the combined bisulfite restriction analysis of the LRE1 sequence in a population-based case-control study of HNSCC from the Boston area. RESULTS: Hypomethylation lead to a significant 1.6-fold increased risk for disease (95% confidence interval, 1.1-2.4), in models controlled for other HNSCC risk factors. Smoking showed a significant differential effect (P < 0.03) on blood relative methylation between cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and low folate intake showed relationships with decreased global methylation, whereas in controls, antibody response to human papillomavirus 16 was associated with an increased global methylation level. DISCUSSION: DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC.
Authors: Hui-Chen Wu; Qiao Wang; Lissette Delgado-Cruzata; Regina M Santella; Mary Beth Terry Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-06-04 Impact factor: 4.254
Authors: Weiliang Qiu; Andrea Baccarelli; Vincent J Carey; Nadia Boutaoui; Helene Bacherman; Barbara Klanderman; Stephen Rennard; Alvar Agusti; Wayne Anderson; David A Lomas; Dawn L DeMeo Journal: Am J Respir Crit Care Med Date: 2011-12-08 Impact factor: 21.405
Authors: L H Lumey; Mary Beth Terry; Lissette Delgado-Cruzata; Yuyan Liao; Qiao Wang; Ezra Susser; Ian McKeague; Regina M Santella Journal: Int J Epidemiol Date: 2011-09-29 Impact factor: 7.196
Authors: Zhong-Zheng Zhu; Lifang Hou; Valentina Bollati; Letizia Tarantini; Barbara Marinelli; Laura Cantone; Allen S Yang; Pantel Vokonas; Jolanta Lissowska; Silvia Fustinoni; Angela C Pesatori; Matteo Bonzini; Pietro Apostoli; Giovanni Costa; Pier Alberto Bertazzi; Wong-Ho Chow; Joel Schwartz; Andrea Baccarelli Journal: Int J Epidemiol Date: 2010-09-15 Impact factor: 7.196
Authors: Heather H Burris; Sheryl L Rifas-Shiman; Andrea Baccarelli; Letizia Tarantini; Caroline E Boeke; Ken Kleinman; Augusto A Litonjua; Janet W Rich-Edwards; Matthew W Gillman Journal: J Dev Orig Health Dis Date: 2012-06 Impact factor: 2.401
Authors: Brock C Christensen; Michele Avissar-Whiting; Lauren G Ouellet; Rondi A Butler; Heather H Nelson; Michael D McClean; Carmen J Marsit; Karl T Kelsey Journal: Clin Cancer Res Date: 2010-05-25 Impact factor: 12.531
Authors: Mukesh Verma; Scott Rogers; Rao L Divi; Sheri D Schully; Stefanie Nelson; L Joseph Su; Sharon A Ross; Susan Pilch; Deborah M Winn; Muin J Khoury Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-12-10 Impact factor: 4.254
Authors: Paula L Hyland; Laura S Burke; Ruth M Pfeiffer; Lisa Mirabello; Margaret A Tucker; Alisa M Goldstein; Xiaohong R Yang Journal: Melanoma Res Date: 2013-02 Impact factor: 3.599