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The Role of Parental and Grandparental Epigenetic Alterations in Familial Cancer Risk

¹ Human Cancer Genetics Program and the Ohio State Comprehensive Cancer Center, Department of Molecular Virology, Immunology, and Medical Genetics, and ² Department of Internal Medicine, The Ohio State University, Columbus, Ohio

Requests for reprints: Amanda Ewart Toland, 998 BRT, 460 West 12th Avenue, Columbus, OH 43210. Phone: 614-247-8185; Fax: 614-688-8675; E-mail: amanda.toland{at}osumc.edu.

Key Words: epigenetics • transgenerational epigenetic inheritance • MLH1 • MSH2

Abstract

Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. These modifications take place throughout development with subsequent events occurring later in adulthood. Recent studies, however, suggest that some epigenetic alterations that influence cancer risk are inherited through the germline from parent to child and are observed in multiple generations. Epigenetic changes may be inherited as Mendelian, non-Mendelian, or environmentally induced traits. Here, we will discuss Mendelian, non-Mendelian, and environmentally induced patterns of multigenerational epigenetic alterations as well as some possible mechanisms for how these events may be occurring. [Cancer Res 2008;68(22):9116–21]