This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Contact me when this article is cited  Related Content  • Related letter  • Similar articles in JAMA  Topic Collections  • Oncology  • Oncology, Other  • Genetics  • Genetic Disorders  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

In Reply: Dr Denic and colleagues extrapolate our findings, which deal with germline homozygosity and low-penetrance susceptibility to common solid tumors, to inbred populations. They then suggest that homozygotes for cancer alleles die prematurely and so it would not be likely to see homozygous cancer alleles.

We assume they are referring to traditional high-penetrance cancer susceptibility alleles, such as RB, TP53, and BRCA1/2, where null murine models are embryonic lethal. Although Rb–/– murine models had been believed to be embryonic lethal in mice, their embryonic lethality is due only to a placental effect.¹ When the extra-embryonic tissues (including placenta) were rescued, Rb–/– mice were shown to be born and viable.¹

Nonetheless, our data are most germane to low-penetrance susceptibility to common cancers in general populations as we studied unrelated white patients of northern and western European ancestry. The most homozygous hotspots did not correspond to regions harboring known high-penetrance . . . [Full Text of this Article]

Charis Eng, MD, PhD
engc@ccf.org

Guillaume Assié, MD, PhD; Thomas LaFramboise, PhD
Genomic Medicine Institute
Cleveland Clinic Foundation
Cleveland, Ohio

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTER

Germline Genomic Homozygosity and Cancer Risk
Srdjan Denic, Nicolaas Nagelkerke, and M. Gary Nicholls
JAMA. 2008;300(2):169-170.
EXTRACT | FULL TEXT