Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were

Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG)n coding for polyglutamine and (GGC)ncoding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. We present here a study of both hAR trinucleotide repeat polymorphisms not only as they relate to the initial diagnosis but also as they are associated with disease progression after therapy. Lymphocyte DNA samples from 178 British Caucasian prostate cancer patients and 195 control individuals were genotyped by PCR for the (CAG)n and (GGC)n polymorphisms in hAR. Univariate Cox proportional hazard analysis indicated that stage, grade and GGC repeat length were individually significant factors associated with disease‐free survival (DFS) and overall survival (OS). The relative risk (RR) of relapse for men with more than 16 GGC repeats was 1.74 (95% CI 1.08–2.79) and of dying from any cause, 1.98 (1.13–3.45). Adjusting for stage and grade, GGC effects remained but were not significant (RRDFS= 1.60, p = 0.052; RROS= 1.65, p = 0.088). The greatest effects were in stage T1‐T2 (RRDFS= 3.56, 95% CI 1.13–11.21) and grade 1 (RRDFS= 6.47, 95% CI 0.57–72.8) tumours. No differences between patient and control allele distributions were found by odds‐ratio analysis, nor were trends with stage or grade evident in the proportion of short CAG alleles. Non‐significant trends with stage and grade were found in the proportion of short GGC alleles. The (GGC)n polymorphism in this population is a significant predictor of disease outcome. Since the (GGC)n effect is strongest in early‐stage tumours, this marker may help forecast aggressive behaviour and could be used to identify those patients meriting more radical treatment. Int. J. Cancer (Pred. Oncol.) 84:458–465, 1999. © 1999 Wiley‐Liss, Inc.

In reviews of malignancy and occupation, cancer of the nose and paranasal sinuses (sinonasal cancer (SNC) is frequently mentioned. In a case-control study of SNC among subjects who died in Connecticut in the period 1935--1975, occupations from death certificates and city directories were compared to job titles taken from previous literature. The results do not support an association of the cancer with nickel (odds ratio = 0.7, 95% confidence limits (CL): 0.4, 1.5) but do support an association with cutting oils (odds ratio = 2.8, 95% CL: 1.4, 5.7) and wood dust (odds ratio = 4.0, 95% CL: 1.5, 10.8). Actual exposure to these agents was not documented, but the results were consistent with other features of the study and with previous literature. In a search for other occupational correlates, SNC was also found to be positively associated with cutters and with construction workers.

Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 ( SMN1 ) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila melanogaster . Using transgenic flies that exclusively express Flag-tagged SMN from its native promoter, we previously found that Gemin2, Gemin3, Gemin5, and all nine classical Sm proteins, including Lsm10 and Lsm11, co-purify with SMN. Here, we show that CG2941 is also highly enriched in the pulldown. Reciprocal co-immunoprecipitation reveals that epitope-tagged CG2941 interacts with endogenous SMN in Schneider2 cells. Bioinformatic comparisons show that CG2941 shares sequence and structural similarity with metazoan Gemin4. Additional analysis shows that three other genes ( CG14164 , CG31950 and CG2371 ) are not orthologous to Gemins 6-7-8, respectively, as previously suggested. In D.melanogaster , CG2941 is located within an evolutionarily recent genomic triplication with two other nearly identical paralogous genes ( CG32783 and CG32786 ). RNAi-mediated knockdown of CG2941 and its two close paralogs reveals that Gemin4 is essential for organismal viability.

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