Two Cancers, One Gene. Why Some People in Families Develop Melanoma or Pancreas Cancer, While Still Others Never Develop Cancer.

Arms (0)

Primary outcomes (1)

1. measure

   Genomic and risk factor differences among family members who share identical predisposing CDKN2A gene mutations, with different phenotypes; will discover patterns of tumorigenesis, tissue specificity, gene-gene, and gene-environment interactions.

   timeFrame

   Each participant provides a research blood sample and completes a questionnaire.This is the duration of their the participant's direct involvement. The duration of generating genotypes and analysis of risk factors may extend up to two years.

   description

   Genotypes of potential modifier genes will be identified in multiple kindreds that feature pancreatic cancer and melanoma and known to carry CDKN2A germline mutations. The investigators will then determine common germline variants in potential CDKN2A mutant carriers using targeted sequencing and search for genetic modifiers by performing Illumina HumanOmni5Exome-4 Beadchip with Infinium LCG on germline DNA. The Illumina microarray contains over 4.5 million markers, of which 528,675 are exonic, and includes over 2.6 million SNPs that would be considered common. The investigators will analyze the genetic and risk factor data collected through the completed surveys by participants using both statistical genetic and machine learning methods. As a means of extension and potential validation, the investigators will then similarly study up to 200 members who are mutation carriers in 39 other CDKN2A mutation-positive kindreds.