Abstract 1859: Breast cancer risk:tp53 genotyping in a Nigerian population

Abstract Background: Women of African descent have a lower incidence of breast cancer than other ethnicities but higher mortality rates. Their tumors are characterized by an earlier age of onset, aggressive behavior, poor prognosis, and molecular characteristics of “triple negative” status (i.e. lacking detectable ER, PR, and HER2/neu expression). These characteristics are also typical of tumors carrying somatic TP53 mutations. Experimental evidence has shown that somatic inactivation of the TP53 pathway is necessary for tumor development. Null or strongly hypomorphic TP53 mutations inherited through the germline are associated with a high likelihood of tumorigenesis. Studies on different ethnic populations show inheritance of TP53 variants, especially the R72P polymorphism, to be associated with risk of tumor formation in breast and other tissues. These observations suggest that TP53 gene activity plays a significant role in promoting tumor development in tissues. Hypothesis: As the TP53 R72P polymorphism has been associated with cancer risk in non-African populations, and patients of African ancestry frequently have tumors with TP53 mutation-like characteristics, we hypothesize the R72P variant may be associated with low-penetrance breast cancer risk in a Nigerian/Yoruba population. In addition, this variant may be associated with the triple negative tumor subtype. Methods: The study is a case-control analysis using 213 breast cancer patients and 213 unaffected controls from the University Hospital in Ibadan, Nigeria. The TP53 R72P genotype was determined by direct sequencing of TP53 exon 4, amplified by PCR from peripheral genomic DNA. Chi-square statistical analysis was used to compare frequencies of individual alleles and genotypes in between cases and controls. Results and Conclusions: 130 cases and 207 controls have been genotyped so far. Genotype frequencies for G/G, G/C, and C/C were 21%, 38%, and 41% in cases and 12%, 46% and 42% in the controls, respectively with a p value of 0.11 and an odds ratio of 1.24 at 95% CL. Preliminary results indicate a trend toward risk associated with the G/G genotype, though these results do not yet reach statistical significance. This analysis may provide important clues to the genetic basis of cancer risk and tumor etiology in patients of African ancestry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1859.