Length and somatic mosaicism of CAG and GGN repeats in the androgen receptor gene and the risk of prostate cancer in men with benign prostatic hyperplasia

The most common malignancy in men worldwide is cancer of the prostate and determinants of prostate cancer [PRCa] risk remain largely unidentified. Many candidate genes may be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. We analysed the polymorphic CAG and GGN repeats sequence in exon 1 of the AR gene to determine if the number of repeats might be an indicator of PRCa risk in patients with BPH. The study evaluated 28 patients who presented with PRCa at least 6 years after the diagnosis of BPH and 56 matched patients with BPH who did not progress to PRCa over a comparable period. This study showed no evidence for association between the size of AR CAG and GGN repeats and the risk of the development of PRCa in patients with BPH. However, BPH patients with AR CAG instability had a 12-fold increased risk in development of PRCa. Conclusions: While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease

Vitamin D. receptor, HER-2 polymorphisms and risk of prostate cancer in men with benign prostate hyperplasia

Prostate cancer [PRCa] is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia [BPH] is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor [VDR] and HER-2 protooncogene have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes could be useful to detect BPH patients that have a higher risk of developing PRCa. This study used a case-control design to assess the predictive value of 3 polymorphisms in VDR [TaqI and FokI] and HER-2 [Val655Ile] to determine the risk of developing PRCa in patients with BPH. Polymorphisms were detected by RFLP analysis. The study evaluated 28 patients who presented with PRCa at least 6 years after the diagnosis of BPH and 56 matched patients with BPH who did not progress to PRCa over a comparable period. The study was carried out in University of Aberdeen, Foresterhill, Aberdeen, United Kingdom in the year 2002. Among the case group, 89% had a TT TaqI genotype, whereas 57% of control had this genotype [odds ratio [OR] = 5.16, 95% confidence interval [CI] = 1.46-18.22]. A similar pattern was seen for the FokI genotype, although this was not statistically significant [OR = 2.33, 95% CI = 0.86-6.29]. The frequency of the HER-2 Ile/Ile genotype was higher in cases [79%] compared to control subjects [66%], although this was not statistically significant [OR = 1.94, 95% CI = 0.67-5.63]. This study shows that the VDR TaqI polymorphism is associated with a group of men with BPH who are at an increase risk of PRCa, providing a potential tool to assist prediction strategies for this important disease

Cancer risks associated with the genes BRCA1 and BRCA2

Inherited predisposition to breast and ovarian cancer, which accounts for about 5 to 10% of these cancers, has been associated with mutations in the BRCA1 and BRCA2 genes. Mutations in both of these genes increase the lifetime risk of developing breast cancer by approximately 80%. Whilst BRCA1 confers a greater predisposition of ovarian cancer, BRCA2 has been associated with male breast cancer. Both genes code for large proteins and display a number of similar features including a large internal exon 11, expressed in similar tissues, and possess a number of similar putative functional domains. Furthermore, both proteins appear to act as tumour suppressor genes and may play a role in the DNA repair process. It is becoming increasingly important to identify families whose cancers may be due to these highly penetrant disease genes. Individuals who undergo predictive genetic testing will need appropriate support and counselling prior to their cancer risk assessment. For those at risk, appropriate counselling, laboratory services, screening and management need to be made available

Familial cancers

Although cancer is common in the general population, only a small proportion is thought to be due to highly penetrant cancer genes. Families with a highly penetrant cancer predisposing gene may be recognised by the presence of a high number of individuals within the family with a particular cancer type, or individuals with features associated with rare inherited cancers, such as retinal changes or multiple colonic polyps. It is likely that there are many other less penetrant genes, which, in combination with environmental influences, will confer a greater lifetime predisposition to cancers. These genes are currently being identified through epidemiological studies