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Discovering the causes of cancer and the means of prevention

Laboratory of Genetic Susceptibility

Understanding the genetic underpinnings of susceptibility to cancer

The Laboratory of Genetic Susceptibility (LGS) performs interdisciplinary research on cancer genetics and susceptibility.

Research Mission

The LGS mission is to understand the biological basis for genetic susceptibility to cancer, including:

  • Identification and characterization of cancer susceptibility alleles
  • Characterization of the scope of genetic mosaicism and its contribution to cancer risk
  • Investigation of the genetic architecture of cancer susceptibility
  • Determination of how germline variation informs our understanding of somatic alterations in cancer

LGS scientists participate in genetic, epidemiologic, clinical and methodological studies of populations, families, and persons at risk for cancer. In addition, they collaborate and consult with experts in statistical genetics, bioinformatics, genetic epidemiology, and molecular epidemiology in interdisciplinary studies.


LGS accepts fellowship applications on an ongoing basis. Meet the current LGS fellows and learn about research training opportunities.


Essential to the mission of the Laboratory is a close collaboration with the NCI-Frederick Cancer Genomics Research Laboratory (CGR). Formerly known as the Core Genotyping Facility (CGF), this laboratory designs and conducts high throughput sequencing, genotyping, and analysis in support of large scale epidemiologic studies.

LGS Highlights

Colli LM, Morton LM, Chanock SJ, et al. Sex-related effect on immunotherapy response: implications and opportunities. JNCI 2019

Machiela MJ, Myers TA, Lyons CJ, et al. Detectible mosaic truncating PPM1D mutations, age and breast cancer risk. J Hum Genet. 2019

Machiela MJ, Hofmann JN, Carreras-Torres R, et al. Genetic variants related to longer telomere length are associated with increased risk of renal cell carcinoma. Eur Urol 2017.

Colli LM, Machiela MJ, Zhang H, et al. Landscape of combination immunotherapy and targeted therapy to improve cancer management. Cancer Res 2017.

Scelo G, Purdue MP, Brown KM, et al. Genome-wide association study identifies multiple risk loci for renal cell carcinoma. Nat Commun 2017.

Chanock S. Stem cells: Subclone wars. Nature 2017.

Machiela MJ and Chanock SJ. The ageing genome, clonal mosaicism and chronic disease. Curr Opin Genet Dev 2017.

Bigot P, Colli LM, Machiela MJ, et al. Functional characterization of the 12p12.1 renal cancer-susceptibility locus implicates BHLHE41 . Nat Commun 2016.

Colli LM, Machiela MJ, Myers TA, et al. Burden of nonsynonymous mutations among TCGA cancers and candidate immune checkpoint inhibitor responses. Cancer Res 2016.

Machiela MJ, Zhou W, Karlins E, et al. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat Commun 2016.

Zhou W, Machiela MJ, Freedman ND, et al. Mosaic loss of chromosome Y is associated with common variation near TCL1A . Nat Genet 2016.