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About the Authors:
Linda M. Liao
* E-mail: [email protected]
Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Paul Brennan
Affiliation: International Agency for Research on Cancer, Lyon, France
Dana M. van Bemmel
Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
David Zaridze
Affiliation: Institute of Carcinogenesis, Moscow, Russian Federation
Vsevolod Matveev
Affiliation: Institute of Carcinogenesis, Moscow, Russian Federation
Vladimir Janout
Affiliation: Palacky University, Olomouc, Czech Republic
Hellena Kollarova
Affiliation: Palacky University, Olomouc, Czech Republic
Vladimir Bencko
Affiliation: Charles University in Prague, Prague, Czech Republic
Marie Navratilova
Affiliation: Masaryk Memorial Cancer Institute, Bmo, Czech Republic
Neonila Szeszenia-Dabrowska
Affiliation: Institute of Occupational Medicine, Lodz, Poland
Dana Mates
Affiliation: Institute of Public Health, Bucharest, Romania
Nathaniel Rothman
Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Paolo Boffetta
Affiliations The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, United States of America, International Prevention Research Institute, Lyon, France
Wong-Ho Chow
Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Lee E. Moore
Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Introduction
Region-specific hypermethylation and global hypomethylation of DNA are associated with carcinogenesis [1]. Aberrant DNA hypermethylation tends to occur in CpG-rich promoter regions and is associated with transcriptional silencing of genes, such as tumor suppressor genes [2]. In contrast, genome-wide DNA hypomethylation occurs primarily in repetitive sequences of DNA, such as heterochromatic regions and retrotransposons [3]. Several studies have observed an association between methylation levels of leukocyte DNA and risk of bladder, breast, and colorectal cancer [4], [5], [6], [7]. However, the association between global methylation levels and renal cell cancer (RCC) has not yet been evaluated.
Long interspersed nuclear elements (LINE-1) are non-long-terminal-repeat (non-LTR) retrotransposons that make up about 17% of the human genome, with ∼500,000 elements normally dispersed throughout the human genome [3], [8]. LINE-1 elements are typically heavily methylated in normal tissues, while LINE-1 hypomethylation has been reported in cancer tissues [9]. Quantification of CpG methylation within LINE-1 elements is an inexpensive high-throughput assay that has been extensively used as a proxy of...