Hereditas 135: 61-63 (2001)
Susceptibility locus for epidermodysplasia verruciformis not linked to cervical cancer in situ ANNA H. BESKOW, JESSICA RONNHOLM, PATRIK K. E. MAGNUSSON and ULF B. GYLLENSTEN Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden Beskow, A. H., Ronnholm, J., Magnusson, P. K. E. and Gyllensten, U. B. 2001. Susceptibility locus for epidermodysplasia verruciformis not linked to cervical cancer in situ.-Hereditas 13.5: 61 -63. Lund, Sweden. ISSN 0018-0661. Accepted November 7, 2001 Cervical cancer is strongly associated with infection by oncogenic forms of human papillomavirus (HPV), mainly HPV 16 and HPV 18. The aim of this study was to test if a locus previously mapped to a region on chromosome 17qter in patients with epidermodysplasia verucciformis (EV) and psoriasis and considered to be responsible for an increased susceptibility to HPV 5, also is linked to increased HPV susceptibility in cervical cancer in situ. We also wanted to test whether HPV 16 positivity cluster in families with cervical cancer. DNA was extracted from formalin fixed biopsies of 224 affecteds from 77 families diagnosed with cervical cancer in situ. Two microsatellite markers (D17S939 and D17S802) containing the locus were genotyped and linkage analysis was performed. No linkage was found to any of the two markers, neither when considering all cancer cases as affecteds nor when only considering HPV 16 infected cancer cases as affecteds in the analysis. We conclude that the susceptibility locus for HPV 5 infections associated with EV and psoriasis does not seem to affect susceptibility to HPV 16, frequently detected in cervical cancer. Also, positivity for HPV 16 did not show a significant clustering in families. Ulf Gyllensten, Departnient of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, SE- 7.51 8.5 Uppsala, Sweden. E-mail:
[email protected]
Oncogenic genital forms of human papilloma virus (HPV), including types such as HPV 16, 18, 31 and 45, have been shown to be a major cause of cervical cancer (WALBOOMERS et al. 1999). Epidemiological studies have demonstrated a familial relative risk of about two for first-degree relatives to affecteds, indicating that genetic risk factors may be important for the development of cervical cancer (MAGNUSSON et al. 1999). Such genetic factors may act indirectly by increasing the susceptibility to HPV infection, thereby increasing the risk of cell transformation and tumor development. Epidermodysplasia verruciformis (EV), a rare, lifelong skin disease, results from an abnormal genetically determined susceptibility to a specific group of related HPVs, including HPV 5 among others (ORTH et al. 1979). HPV 5 has an oncogenic potential and is often found in cancers of the skin (JABLONSKA et al. 1972; ORTH et al. 1979). Recently, genetic studies based on homozygosity mapping in a set of three consanguineous families, comprising six EV patients, reported linkage to a 1 centiMorgan (cM) region between the markers D17S939 and D17S802 on chromosome 17qter (RAMOZet al. 1999). This region overlaps with that previously shown to contain a locus for susceptibility to familial psoriasis (TOMFOHRDE et al. 1994). It has been shown that patients suffering from psoriasis are frequently infected by
HPV 5 (FAVREet al. 1998). As both EV and cervical cancer are associated with HPV infection, albeit with different HPV types, the possibility exist that the locus found to affect susceptibility to EV also could be involved in cervical cancer. In this study we used a set of Swedish families with cervical cancer in situ to study if markers for the susceptibility locus for EV show linkage to cervical cancer in situ. MATERIALS AND METHODS Family material
Families with more than three affected (diagnosed with cervical cancer in situ) were identified (MAGNUSSON et al. 1999). Biopsies were collected from the Swedish national pathology archives. A total of 224 individuals from 77 families were selected. Only families where a biopsy could be obtained from at least two affected members were included. D N A extraction from biopsies
One thin (1 mm) section was sliced from the formalin fixed and paraffin embedded biopsies and put into a 1.5 ml eppendorf tube. DNA was extracted from the section according to the protocol previously described for formalin fixed paraffin embedded material (JOSEFSSONet al. 1998).
