A Case-Control Comparison of the Androgen Receptor Polyglutamine Tract in an Egyptian Male Breast Cancer Population
Male Breast Cancer (MBC) is a relatively rare disease in America, accounting for slightly less than 1% of all breast cancers and being influenced by hereditary factors. Rates of MBC in Africa appear to be greater and more variable than in the US. MBC is estimated to comprise 7% of breast cancer cases in Uganda, reported by the Middle East Cancer Consortium as 1.3% of breast cancers in Egypt, and found by previous CEESP students to be 2.6% of all breast cancers in Morocco. CEESP exploratory studies using 201 medical records from Egypt (47 with corresponding tissue) and 129 records from Morocco (19 with tissue) of MBC patients have helped to explain some of the variability in rates. BRCA2 mutations (an established risk factor), for example, were found in 26.3% of Morocco MBC cases but only in 23.1% of Egyptian MBC cases. This study aims to investigate the role of molecular markers, specifically the Androgen Receptor (AR) polyglutamine tract (QT) length, in MBC. The QT is a highly variable region in the AR gene; a long QT results in a weaker AR. Since the AR is protective against unrestrained cellular division in breast tissue, we expect to see longer QT's more represented in a population with MBC compared to unaffected controls.
The 47 Egyptian MBC cases were analyzed for this polymorphism. Normal tissue was excised from formalin-fixed paraffin-embedded tissue sections and genomic DNA extracted. Amplification through polymerase chain reaction with fluorescently labeled 6-FAM primers followed by amplified fragment length polymorphism analysis reveals the QT length. For the control series, blood from 45 older Egyptians without known prostate cancer and without a family history of MBC was collected and analyzed similarly.
44 of the MBC cases yielded a readable QT length. The average age of these cases is 59.42 years. The average QT length is 19.45 (Ïƒ = 2.79). Of 43 readable non-MBC controls, the average age is 57.49 and the average QT length is 19.30 (Ïƒ = 4.23). A t-test between the cases and controls does not show that the MBC patients have a longer average QT than the healthy Egyptians (p = 0.84). However, it is interesting to note that the distribution of QT lengths is different among cases and controls. Short QT lengths are prevalent among cases (6 of the controls have QT lengths â‰¤14) but almost absent among cases (only 1 of the cases has a QT length â‰¤14), suggesting a possible protective effect of short QT's in MBC.
Enrollment of additional controls is ongoing. Analyses will be performed on the expanded groups and reported. Similar studies on subjects from Morocco and Uganda will provide a more comprehensive analysis into the QT length-MBC relationship.
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