Single nucleotide polymorphism patterns associated with a cancer resistant phenotype

Abstract

Background and aims

In this study ten mouse strains representing ~90% of genetic diversity in laboratory mice (B6C3F1/J, C57BL/6J, C3H/HeJ, A/J, NOD.B1oSnH2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ) were examined to identify the mouse strain with the lowest incidence of cancer. The unique single polymorphisms (SNPs) associated with this low cancer incidence are reported.

Methods

Evaluations of cancer incidence in the 10 mouse strains were based on gross and microscopic diagnosis of tumors. Single nucleotide polymorphisms (SNPs) in the coding regions of the genome were derived from the respective mouse strains located in the Sanger mouse sequencing database and the B6C3F1/N genome from the National Toxicology Program (NTP).

Results

The WSB strain had an overall lower incidence of both benign and malignant tumors compared to the other mouse strains. At 2 years, the incidence of total malignant tumors (Poly-3 incidence rate) ranged from 2% (WSB) to 92% (C3H) in males, and 14% (WSB) to 93% (NZO) in females, and the total incidence of benign and malignant tumor incidence ranged from 13% (WSB) to 99% (C3H) in males and 25% (WSB) to 96% (NOD) in females. Single nucleotide polymorphism (SNP) patterns were examined in the following strains: B6C3F1/N, C57BL/6J, C3H/HeJ, 129S1/SvImJ, A/J, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. We identified 7519 SNPs (involving 5751 Ensembl transcripts of 3453 Ensembl Genes) that resulted in a unique amino acid change in the coding region of the WSB strain.

Conclusions

The inherited genetic patterns in the WSB cancer-resistant mouse strain occurred in genes involved in multiple cell functions including mitochondria, metabolic, immune, and membrane-related cell functions. The unique SNP patterns in a cancer resistant mouse strain provides insights for understanding and developing strategies for cancer prevention.