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A Genetic Predisposition?

Mark C. Loury, MD; Michael E. Johns, MD; Betty S. Danes, MD, PhD

Arch Otolaryngol Head Neck Surg. 1987;113(11):1230-1233.

Abstract
• The role of heredity in the cause of head and neck cancer has not been clarified. Contrary to the autosomal-dominant heritable cancer syndromes, there is no clear genetic pattern seen in oropharyngeal or laryngeal squamous cell carcinoma. Pedigree data demonstrating clusters of affected relatives suggest that some head and neck squamous cell cancers result from an interaction between environmental factors and germinal predisposition. Though no genetic marker has been described for head and neck epidermoid carcinomas, some heritable single tumor syndromes demonstrate increased amounts of hyperdiploidy (defined as a metaphase with more than 46 chromosomes exclusive of 92) in in vitro cultures of dermal fibroblasts. In the present study, dermal fibroblasts were cultured from 30 patients with biopsy-proved oropharyngeal and laryngeal squamous cell cancer. Compared with the percentage of cells with in vitro hyperdiploidy (IVH) of 0% to 1% in 155 clinically normal individuals without a family cancer history, 13 (43%) of these 30 patients had significantly elevated (7% to 12%) IVH. Six of the seven clinically affected women had IVH, a proportion significantly greater than that for the men. In vitro hyperdiploidy remained stable for each assayed cell line from the third through sixth passage. Each patient's IVH percentage of dermal and oropharyngeal fibroblasts remained nearly constant varying 0% to 1%. The stability of the hyperdiploid fraction independent of the biopsy site eliminates local factors as the sources of the elevated IVH. Since IVH is considered to be an in vitro expression of a heritable pre-disposition to develop carcinoma, the observation of IVH in patients with oropharyngeal and laryngeal epidermoid carcinomas suggests that some individuals have a propensity for epithelial neoplasia when exposed to appropriate carcinogens.

(Arch Otolaryngol Head Neck Surg 1987;113:1230-1233)

Author Affiliations
From the Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins Hospital, Baltimore (Drs Loury and Johns), and the Laboratory for Cell Biology, Department of Medicine, Cornell University Medical College, New York (Dr Danes).

Footnotes
Accepted for publication July 7, 1987.

Read before the American Society for Head and Neck Surgery, Denver, April 28, 1987.

Reprint requests to Department of Otolaryngology—Head and Neck Surgery, The Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 20205 (Dr Loury).

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