Head and neck cancer in young adults and nonsmokers: Study of cancer susceptibility by genome-wide high-density SNP microarray mapping

Abstract

Conclusion. Our results raise the question as to whether specific patterns of ‘germline loss of heterozygosity (LOH)’ could contribute to the genetic susceptibility for head and neck squamous cell carcinoma (HNSCC). Objectives. HNSCC usually occurs in older individuals with a history of smoking. However, about 5% of HNSCC patients have never used tobacco or develop this disease at an exceptionally young age. Therefore, genetic susceptibility must contribute significantly to HNSCC risk. The objective was to introduce a novel approach that might help to unveil candidate genes contributing to cancer predisposition and to identify individuals at risk for HNSCC, and to present our observations with this method in a specific group of patients. Methods: High-resolution SNP (single-nucleotide polymorphism) microarray mapping for homozygous stretches in germline DNA was performed in 12 patients who appeared particularly susceptible to develop HNSCC, because they were exceptionally young or never users of tobacco. Results: We could identify strings of consecutive homozygous SNPs that were much longer than would be expected to appear by chance alone, indicating regions of DNA deletions that we named germline LOH.

Keywords::

• Genetic susceptibility
• loss of heterozygosity
• risk factors

Acknowledgment

This work was funded by the Clotten Foundation, Freiburg, Germany (Birkenhäger/RB 05–09). We thank the patients for their encouragement, and Sigrid Weis for excellent technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.