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Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

See Also ADM001348, Thermal Materials Workshop 2001, held in Cambridge, UK on May 30-June 1, 2001. The original document contains color images. Contains viewgraphs only. Additional papers can be downloaded from: http://www-mech.eng.cam.ac.uk/onr

Background: Globally there is a lack of a standardised assessment process prior to the initiation of gender affirming medical interventions and consequently there is a discrepancy in this process among different transgender health services. Aim: The main objective of this study is to investigate the outcome of the initial assessment process at a national transgender health service. Method: The outcome of people over the age of 17 years, assessed at a large national transgender health service in the United Kingdom during a two year period was categorised into: 1) recommendation for cross-sex hormone treatment, or: 2) no recommendation for cross-sex hormone treatment. In addition, 200 case notes were reviewed in order to investigate the level of agreement between the two clinicians involved in the assessment process. Results: During the study period a total of 617 people completed their assessment at the service. Following assessment 380 (61.6%) patients were recommended for cross-sex hormone treatment, leaving 237 (38.4%) patients who required a longer assessment period or were discharged. The factors associated with being recommended for cross-sex hormone treatment were: having socially transitioned, not smoking, having initiated cross-sex hormones prior to assessment, being older, and assigned male at birth. Out of the 200 case notes reviewed, agreement between assessor 1 and 2 (3 months apart) was found in 88 % (n= 176) of the cases. Discussion: Although the results of the study may not be generalizable to other international centres, questioning the assessment process and the role of the assessors is important to ensure treatment is offered in a timely and efficient manner. The findings from this study suggest that the routine inclusion of two assessors needs to be reviewed.

Background: Globally there is a lack of a standardised assessment process prior to the initiation of gender affirming medical interventions and consequently there is a discrepancy in this process among different transgender health services. Aim: The main objective of this study is to investigate the outcome of the initial assessment process at a national transgender health service. Method: The outcome of people over the age of 17 years, assessed at a large national transgender health service in the United Kingdom during a two year period was categorised into: 1) recommendation for cross-sex hormone treatment, or: 2) no recommendation for cross-sex hormone treatment. In addition, 200 case notes were reviewed in order to investigate the level of agreement between the two clinicians involved in the assessment process. Results: During the study period a total of 617 people completed their assessment at the service. Following assessment 380 (61.6%) patients were recommended for cross-sex hormone treatment, leaving 237 (38.4%) patients who required a longer assessment period or were discharged. The factors associated with being recommended for cross-sex hormone treatment were: having socially transitioned, not smoking, having initiated cross-sex hormones prior to assessment, being older, and assigned male at birth. Out of the 200 case notes reviewed, agreement between assessor 1 and 2 (3 months apart) was found in 88 % (n= 176) of the cases. Discussion: Although the results of the study may not be generalizable to other international centres, questioning the assessment process and the role of the assessors is important to ensure treatment is offered in a timely and efficient manner. The findings from this study suggest that the routine inclusion of two assessors needs to be reviewed.

Background: Globally there is a lack of a standardised assessment process prior to the initiation of gender affirming medical interventions and consequently there is a discrepancy in this process among different transgender health services. Aim: The main objective of this study is to investigate the outcome of the initial assessment process at a national transgender health service. Method: The outcome of people over the age of 17 years, assessed at a large national transgender health service in the United Kingdom during a two year period was categorised into: 1) recommendation for cross-sex hormone treatment, or: 2) no recommendation for cross-sex hormone treatment. In addition, 200 case notes were reviewed in order to investigate the level of agreement between the two clinicians involved in the assessment process. Results: During the study period a total of 617 people completed their assessment at the service. Following assessment 380 (61.6%) patients were recommended for cross-sex hormone treatment, leaving 237 (38.4%) patients who required a longer assessment period or were discharged. The factors associated with being recommended for cross-sex hormone treatment were: having socially transitioned, not smoking, having initiated cross-sex hormones prior to assessment, being older, and assigned male at birth. Out of the 200 case notes reviewed, agreement between assessor 1 and 2 (3 months apart) was found in 88 % (n= 176) of the cases. Discussion: Although the results of the study may not be generalizable to other international centres, questioning the assessment process and the role of the assessors is important to ensure treatment is offered in a timely and efficient manner. The findings from this study suggest that the routine inclusion of two assessors needs to be reviewed.

Background: Globally there is a lack of a standardised assessment process prior to the initiation of gender affirming medical interventions and consequently there is a discrepancy in this process among different transgender health services. Aim: The main objective of this study is to investigate the outcome of the initial assessment process at a national transgender health service. Method: The outcome of people over the age of 17 years, assessed at a large national transgender health service in the United Kingdom during a two year period was categorised into: 1) recommendation for cross-sex hormone treatment, or: 2) no recommendation for cross-sex hormone treatment. In addition, 200 case notes were reviewed in order to investigate the level of agreement between the two clinicians involved in the assessment process. Results: During the study period a total of 617 people completed their assessment at the service. Following assessment 380 (61.6%) patients were recommended for cross-sex hormone treatment, leaving 237 (38.4%) patients who required a longer assessment period or were discharged. The factors associated with being recommended for cross-sex hormone treatment were: having socially transitioned, not smoking, having initiated cross-sex hormones prior to assessment, being older, and assigned male at birth. Out of the 200 case notes reviewed, agreement between assessor 1 and 2 (3 months apart) was found in 88 % (n= 176) of the cases. Discussion: Although the results of the study may not be generalizable to other international centres, questioning the assessment process and the role of the assessors is important to ensure treatment is offered in a timely and efficient manner. The findings from this study suggest that the routine inclusion of two assessors needs to be reviewed.