Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men.

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Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research. Patient consent for publication Not required. Provenance and peer review Commissioned; internally peer reviewed.

We thank Goulielmos et al 1 for their interests on our article entitled 'Risk of systemic lupus erythematosus (SLE) in patients with idiopathic thrombocytopenic purpura (ITP): a population-based cohort study'. 2 Goulielmos et al raised possible mechanism and explanation about the link of ITP and SLE. We appreciated their review and comments on sensitised platelets, shared genetic background and similar molecular signatures of these two diseases. We also agree that these genetic and molecular background, especially interferon signatures in ITP might lead to development autoimmune diseases, such as SLE.In this study, we use a big data approach to explore the linkage of ITP and SLE and demonstrated strong association of these two diseases. It is not our purpose to look at the mechanism of this association. We appreciate those creative comments and hypothesis that Goulielmos et al proposed. A recent study also found active role of platelet activation in pathogenesis of SLE. 3 It definitely need further bench works to prove above hypothesised mechanism.One possible linkage which Goulielmos et al did not mention is the environmental factors, especially infection. Besides wellknown virus, such as Epstein-Barr virus, cytomegalovirus and parvovirus B19, in our previous studies, we also found that SLE is associated various micro-organisms, including human Papillomavirus, scrub typhus, 4 Helicobacter pylori, 5 Mycoplasma pneumonia and non-typhoid Salmonella (data in submission). We think that SLE and other autoimmune diseases all had strong interaction with genetic and environmental factors.In conclusion, we agree that SLE is a complex disease spectrum with various phenotypes. ITP and certain subtypes of SLE might share molecular and genetic backgrounds. Clinician should recognise ITP might be a subtype of subclinical SLE in managing patients.