ABSTRACT
BACKGROUND: Cervical carcinoma is the second most common malignancy among women worldwide. The highest incidence rates are observed in developing countries. The increased susceptibility to cervical carcinoma in high incidence populations may result from several factors including human papillomavirus exposure and both inherited and acquired genetic traits. Using comparative molecular analysis of cervical carcinomas from Surinam, a high incidence area, and the Netherlands, a low incidence area, distinct molecular genetic profiles were studied in two populations with contrasting risk for the disease. METHODS: In the two populations, the authors compared allelic loss as a marker for the involvement of putative tumor suppressor genes in 40 and 67 carcinoma specimens from Surinam and the Netherlands, respectively. Loss of heterozygosity (LOH) analysis was performed using polymorphic microsatellite markers at sites of known tumor suppressor genes (17p [p53], 13q [Rb, BRCA2], 16q [E-cadherin], and 17q [BRCA1]) and at chromosomes 3p, 6p, 6q, and 11q, which frequently are lost in cervical carcinoma. RESULTS: Remarkable differences in LOH were found between both populations. The most prominent observation was the extremely high frequency of LOH, up to 72%, in the region of the major histocompatibility complex on chromosome 6p in specimens from Surinam. In the group of specimens from the Netherlands, only 45% of LOH was observed at this locus. In addition, LOH was detected significantly more frequently at 6q and 13q in the cases from Surinam whereas LOH was found more frequently at 17p in cases from the Netherlands. CONCLUSIONS: The results of the current study show that heterogeneity exists in tumor-associated somatic genetic alterations between these two populations that may be indicative of the existence of multiple genetic pathways in cervical tumorigenesis.