Identification of a novel NBN truncating mutation in a family with hereditary prostate cancer

Nibrin (NBN), located on chromosome 8q21 is a gene involved in DNA double-strand break repair that has been implicated in the rare autosomal recessive chromosomal instability syndrome known as Nijmegen Breakage Syndrome. NBS is characterized by specific physical characteristics (microcephaly and dysmorphic facies), immunodeficiency, and increased risk of malignancy. Individuals who are heterozygous for NBN mutations are clinically asymptomatic, but may display an elevated risk for certain cancers including, but not limited to, ovarian and prostate cancer as well as various lymphoid malignancies. In this study, 94 unrelated familial prostate cancer cases from the University of Michigan Prostate Cancer Genetics Project (n= 54) and Johns Hopkins University (n=40) were subjected to targeted next-generation sequencing of the exons, including UTRs, of NBN. One individual of European descent, diagnosed with prostate cancer at age 52, was identified to have a heterozygous 2117 C>G mutation in exon 14 of the gene, that results in a premature stop at codon 706 (S706X). Sequencing of germline DNA from additional male relatives showed partial co-segregation of the NBN S706X mutation with prostate cancer. This NBN mutation was not observed among 2768 unrelated European men (1859 with prostate cancer and 909 controls). NBN is involved in double-strand break repair as a component of the MRE11 (meiotic recombination 11)/RAD50/NBN genomic stability complex. The S706X mutation truncates the protein in a highly conserved region of NBN near the MRE11 binding site, thus suggesting a role for rare NBN mutations in prostate cancer susceptibility

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Characterizing mobility patterns and malaria risk factors in semi-nomadic populations of Northern Kenya.

While many studies have characterized mobility patterns and disease dynamics of settled populations, few have focused on more mobile populations. Highly mobile groups are often at higher disease risk due to their regular movement that may increase the variability of their environments, reduce their access to health care, and limit the number of intervention strategies suitable for their lifestyles. Quantifying the movements and their associated disease risks will be key to developing interventions more suitable for mobile populations. Turkana, Kenya is an ideal setting to characterize these relationships. While the vast, semi-arid county has a large mobile population (>60%) and was recently shown to have endemic malaria, the relationship between mobility and malaria risk in this region has not yet been defined. Here, we worked with 250 semi-nomadic households from four communities in Central Turkana to 1) characterize mobility patterns of travelers and 2) test the hypothesis that semi-nomadic individuals are at greater risk of malaria exposure when migrating with their herds than when staying at their semi-permanent settlements. Participants provided medical and travel histories, demographics, and a dried blood spot for malaria testing before and after the travel period. Further, a subset of travelers was given GPS loggers to document their routes. Four travel patterns emerged from the logger data, Long Term, Transient, Day trip, and Static, with only Long Term and Transient trips being associated with malaria cases detected in individuals who carried GPS devices. After completing their trips, travelers had a higher prevalence of malaria than those who remained at the household (9.2% vs 4.4%), regardless of gender and age. These findings highlight the need to develop intervention strategies amenable to mobile lifestyles that can ultimately help prevent the transmission of malaria

Characteristics of travelers and trip-types, overall and stratified by GPS carrier status.

Characteristics of travelers and trip-types, overall and stratified by GPS carrier status.</p

GPS carrying travelers whose trips were categorized as transient.

50% of nights were spent at transient camps (defined as camps with (TIF)</p

Characteristics of travelers and remainers (all and those who tested PCR+ for malaria after migration) % (number/N); median (IQR).

Characteristics of travelers and remainers (all and those who tested PCR+ for malaria after migration) % (number/N); median (IQR).</p

Using reported departure and return dates instead of the enrollment and follow-up dates.

Using reported departure and return dates instead of the enrollment and follow-up dates.</p