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BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

BACKGROUND: Most studies of football injuries include professional players and data have been collected in without a single validated, standardised tool. We aimed to develop a new standardised questionnaire for assessing injuries among non-professional footballers and pilot its use. METHOD: A questionnaire was developed using input from footballers, healthcare professionals and triangulation from the literature. The new tool was piloted among players representing amateurs and semi-professionals. Their comments were used iteratively to improve the instrument. RESULTS: The development phase produced a 33-item questionnaire collecting quantitative and qualitative data. In the pilot phase, 42 questionnaires were distributed, 34 (81%) returned. Respondents reported total of 273 football-related injuries, 114 affecting the foot/ankle (70 at the ankle and 44 at the foot). In total, 44% of respondents had suffered one or more foot/ankle injuries in the past 12 months. CONCLUSION: We developed a new standardised tool which we found to be well-completed by young male footballers in semi-professional and amateur settings with an excellent response rate. Our results suggested that foot/ankle injuries were common, larger studies in non-professionals are needed to identify risk factors for injury and develop pragmatic advice for prevention. Keywords: Soccer; Language: en