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Letters
July 9, 2008

Germline Genomic Homozygosity and Cancer Risk—Reply

JAMA. 2008;300(2):169-170. doi:10.1001/jama.300.2.170

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

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