Molecular Basis of Cancer Susceptibility

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Both the candidate gene approach and genome-wide approach are being employed to identify the genetic predisposition of "common" cancers, such as gastric and lung cancers or leukemia, as a part of the Millennium Genome Project being conducted as a teamwork of the Center for Medical Genomics, several other Divisions of the Research Institute and Hospitals.

Genetic variations are expected to affect phenotypes such as common disease risks and drug response differences. In order to enumerate the genetic variations and mutations among various types of cancer phenotypes, resequencing of more than 300 candidate genes is in progress. The genes were selected from various pathways: DNA repair pathways, immune system, cell cycle regulation, drug-metabolizing systems, oncogenes and tumor suppressor genes. During the development of the computer system for automated genetic variation detection, a new algorithm for detecting insertions and deletions (indels) was developed and the patent application of the algorithm is filed to the Japan Patent Office.

As the first application of the our candidate gene SNP collection, non-synonymous SNPs (single nucleotide substitution that alters the coded amino acid) from DNA repair genes were examined for associations with lung cancer risk by collaboration with Cancer Biology Division, NCCRI.