Probable post-traumatic stress disorder and harmful alcohol use among male members of the British Police Forces and the British Armed Forces: a comparative study.

Background: British Armed Forces' and Police Forces' personnel are trained to operate in potentially traumatic conditions. Consequently, they may experience post-traumatic stress disorder (PTSD), which is often comorbid with harmful alcohol use. Objective: We aimed to assess the proportions, and associations, of probable PTSD and harmful alcohol use among a covariate-balanced sample of male military personnel and police employees. Methods: Proportions of probable PTSD, harmful alcohol use, and daily binge drinking, were explored using data from the police Airwave Health Monitoring Study (2007-2015) (N = 23,826) and the military Health and Wellbeing Cohort Study (phase 2: 2007-2009, phase 3: 2014-2016) (N = 7,399). Entropy balancing weights were applied to the larger police sample to make them comparable to the military sample on a range of pre-specified variables (i.e. year of data collection, age and education attainment). Multinomial and logistic regression analyses determined sample differences in outcome variables, and associated factors (stratified by sample). Results: Proportions of probable PTSD were similar in military personnel and police employees (3.67% vs 3.95%), although the large sample size made these borderline significant (Adjusted Odds Ratio (AOR): 0.84; 95% Confidence Intervals (CI): 0.72 to 0.99). Clear differences were found in harmful alcohol use among military personnel, compared to police employees (9.59% vs 2.87%; AOR: 2.79; 95% CI: 2.42 to 3.21). Current smoking, which was more prevalent in military personnel, was associated with harmful drinking and binge drinking in both samples but was associated with PTSD in military personnel only. Conclusions: It is generally assumed that both groups have high rates of PTSD from traumatic exposures, however, low proportions of PTSD were observed in both samples, possibly reflecting protective effects of unit cohesion or resilience. The higher level of harmful drinking in military personnel may relate to more prominent drinking cultures or unique operational experiences.

Antecedentes: El personal de las fuerzas armadas británicas y de la policía británica está entrenado para operar en condiciones potencialmente traumáticas. Consecuentemente, pueden experimentar trastorno de estrés postraumático (TEPT), el cual es frecuentemente comórbido con uso nocivo de alcohol.Objetivo: Buscamos evaluar las proporciones, y asociaciones, del probable TEPT y del uso nocivo de alcohol en una muestra balanceada por covariables de personal masculino, militares y empleados de policía.Métodos: Las proporciones de probable TEPT, uso nocivo de alcohol y atracones diarios de alcohol, fueron exploradas utilizando datos del estudio Airwave Health Monitoring Study de la policía (2007-2015) (N=23,826) y del estudio militar Health and Wellbeing Cohort Study (fase 2: 2007-2009, fase 3: 2014-2016) (N=7,399). Se aplicaron pesos de balance de entropía a la muestra más grande, de policía, para hacerla comparable a la muestra militar en un rango de variables pre-especificadas (ej. año de recolección de datos, edad y logros educacionales). Los análisis multinomiales y de regresión logística determinaron diferencias muestrales en las variables de resultado, y en los factores asociados (estratificados por muestra).Resultados: Las proporciones de TEPT probable fueron similares en el personal militar y los empleados de policía (3,67% vs 3,95%), aunque el gran tamaño muestral hizo fuera significativo al límite (Razón de probabilidades ajustada (AOR): 0.84; Intervalo de Confianza (IC) de 95%: 0.72 a 0.99). Se encontraron claras diferencias en el uso nocivo de alcohol entre el personal militar, comparado a los empleados de policía (9,59% vs 2.87%; AOR: 2.79; IC 95%: 2.42 a 3.21). El consumo actual de tabaco, que fue más prevalente en el personal militar, se asoció a consumo nocivo de alcohol y a atracones de alcohol en ambas muestras, pero se asoció a TEPT sólo en el personal militar.Conclusiones: Generalmente se asume que ambos grupos tienen altas tasas de TEPT desde la exposición traumática, sin embargo, se observó una baja proporción de TEPT en ambas muestras, lo que probablemente refleja el efecto protector de la cohesión de unidad o la resiliencia. El mayor nivel de consumo nocivo de alcohol en el personal militar puede estar relacionado una cultura de consumo de alcohol más prominente o a experiencias operacionales únicas.

Post-deployment screening for mental disorders and tailored advice about help-seeking in the UK military: a cluster randomised controlled trial.

BACKGROUND: The effectiveness of post-deployment screening for mental disorders has not been assessed in a randomised controlled trial. We aimed to assess whether post-deployment screening for post-traumatic stress disorder (PTSD), depression, anxiety, or alcohol misuse was effective. We defined screening as the presumptive identification of a previously unrecognised disorder using tests to distinguish those who probably had the disorder from those who probably did not so that those people with a probable disorder could be referred appropriately, and assessed effectiveness and consequences for help-seeking by the odds ratio at follow-up between those receiving tailored help-seeking advice and those who received general mental health advice. METHODS: We did a cluster randomised controlled trial among Royal Marines and Army personnel in the UK military after deployment to Afghanistan. Platoons were randomly assigned (1:1 initially, then 2:1) by stratified block randomisation with randomly varying block sizes of two and four to the screening group, which received tailored help-seeking advice, or the control group, which received general mental health advice. Initial assessment took place 6-12 weeks after deployment; follow-up assessments were done 10-24 months later. Follow-up measures were the PTSD Checklist-Civilian Version, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 scale, Alcohol Use Disorder Identification Test (AUDIT), and self-reported help-seeking from clinical and welfare providers comparing those receiving tailored advice and those receiving only general advice. All participants and all investigators other than the person who analysed the data were masked to allocation. The primary outcomes were PTSD, depression or generalised anxiety disorder, and alcohol misuse at follow-up. A key secondary outcome was assessment of whether post-deployment screening followed by tailored advice would modify help-seeking behaviour. Comparisons were made between screening and control groups, with primary analyses by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN19965528. FINDINGS: Between Oct 24, 2011, and Oct 31, 2014, 434 platoons comprising 10 190 personnel were included: 274 (6350 personnel) in the screening group and 160 (3840 personnel) in the control group. 5577 (88%) of 6350 personnel received screening and 3996 (63%) completed follow-up, whereas 3149 (82%) of 3840 received the control questionnaire and 2369 (62%) completed follow-up. 1958 (35%) of 5577 personnel in the screening group declined to see the tailored advice, but those with PTSD (83%) or anxiety or depression (84%) were more likely than non-cases (64%) to view the advice (both p<0·0001). At follow-up, there were no significant differences in prevalence between groups for PTSD (adjusted odds ratio 0·92, 95% CI 0·75-1·14), depression or anxiety (0·91, 0·71-1·16), alcohol misuse (0·88, 0·73-1·06), or seeking support for mental disorders (0·92, 0·78-1·08). INTERPRETATION: Post-deployment screening for mental disorders based on tailored advice was not effective at reducing prevalence of mental health disorders nor did it increase help-seeking. Countries that have implemented post-deployment screening programmes for mental disorders should consider monitoring the outcomes of their programmes. FUNDING: The US Army Medical Research and Materiel Command-Military Operational Medicine Research Program (USAMRMC-MOMRP).

A genome-wide association study identifies susceptibility loci for Wilms tumor.

Wilms tumor is the most common renal malignancy of childhood. To identify common variants that confer susceptibility to Wilms tumor, we conducted a genome-wide association study in 757 individuals with Wilms tumor (cases) and 1,879 controls. We evaluated ten SNPs in regions significantly associated at P < 5 × 10(-5) in two independent replication series from the UK (769 cases and 2,814 controls) and the United States (719 cases and 1,037 controls). We identified clear significant associations at 2p24 (rs3755132, P = 1.03 × 10(-14); rs807624, P = 1.32 × 10(-14)) and 11q14 (rs790356, P = 4.25 × 10(-15)). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate association signals at 5q14, 22q12 and Xp22.

Gene-gene interactions in breast cancer susceptibility.

There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 × 10(-4); ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 × 10(-4); CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation.

Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer.

We conducted a genome-wide association study for testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected individuals and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three new susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5, which has previously been associated with multiple other cancers (rs4635969, OR=1.54, P=1.14x10(-23); rs2736100, OR=1.33, P=7.55x10(-15)). We also identified a locus on chromosome 12 (rs2900333, OR=1.27, P=6.16x10(-10)) that contains ATF7IP, a regulator of TERT expression. Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice.

Mutation and association analysis of GEN1 in breast cancer susceptibility.

GEN1 was recently identified as a key Holliday junction resolvase involved in homologous recombination. Somatic truncating GEN1 mutations have been reported in two breast cancers. Together these data led to the proposition that GEN1 is a breast cancer predisposition gene. In this article we have formally investigated this hypothesis. We performed full-gene mutational analysis of GEN1 in 176 BRCA1/2-negative familial breast cancer samples and 159 controls. We genotyped six SNPs tagging the 30 common variants in the transcribed region of GEN1 in 3,750 breast cancer cases and 4,907 controls. Mutation analysis revealed one truncating variant, c.2515_2519delAAGTT, which was present in 4% of cases and 4% of controls. We identified control individuals homozygous for the deletion, demonstrating that the last 69 amino acids of GEN1 are dispensable for its function. We identified 17 other variants, but their frequency did not significantly differ between cases and controls. Analysis of 3,750 breast cancer cases and 4,907 controls demonstrated no evidence of significant association with breast cancer for six SNPs tagging the 30 common GEN1 variants. These data indicate that although it also plays a key role in double-strand DNA break repair, GEN1 does not make an appreciable contribution to breast cancer susceptibility by acting as a high- or intermediate-penetrance breast cancer predisposition gene like BRCA1, BRCA2, CHEK2, ATM, BRIP1 and PALB2 and that common GEN1 variants do not act as low-penetrance susceptibility alleles analogous to SNPs in FGFR2. Furthermore, our analyses demonstrate the importance of undertaking appropriate genetic investigations, typically full gene screening in cases and controls together with large-scale case-control association analyses, to evaluate the contribution of genes to cancer susceptibility.

Genome-wide association study identifies five new breast cancer susceptibility loci.

Breast cancer is the most common cancer in women in developed countries. To identify common breast cancer susceptibility alleles, we conducted a genome-wide association study in which 582,886 SNPs were genotyped in 3,659 cases with a family history of the disease and 4,897 controls. Promising associations were evaluated in a second stage, comprising 12,576 cases and 12,223 controls. We identified five new susceptibility loci, on chromosomes 9, 10 and 11 (P = 4.6 x 10(-7) to P = 3.2 x 10(-15)). We also identified SNPs in the 6q25.1 (rs3757318, P = 2.9 x 10(-6)), 8q24 (rs1562430, P = 5.8 x 10(-7)) and LSP1 (rs909116, P = 7.3 x 10(-7)) regions that showed more significant association with risk than those reported previously. Previously identified breast cancer susceptibility loci were also found to show larger effect sizes in this study of familial breast cancer cases than in previous population-based studies, consistent with polygenic susceptibility to the disease.