We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America; we detected 8 loci (P<5x10–8), 7 of which are novel for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2/TRIM5). Oral cancer was associated with two new regions 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer loci: 9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region and classical HLA allele imputation revealed a protective association with the class II haplotype DRB1*1301-DQA1*0103-DQB1*0603 (odds ratio (OR)=0.59, P=2.7x10–9). Stratified analyses on a subgroup of oropharyngeal cases with human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR=0.23, P=1.6x10–6) compared to HPV-negative cancers (OR=0.75, P=0.16).

This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

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Background Prescribing of systemic antibiotics in general and of cephalosporins in particular in German paediatric outpatients has previously been reported to be higher than in other European countries. Aim Our objective was to assess recent trends in antibiotic prescribing in German children. Methods This study was conducted as consecutive annual cross-sectional analyses and included all children aged 0–14 years (n = 9,389,183 in 2018) covered by statutory health insurance in Germany. Annual antibiotic prescription rates from 2010 to 2018 were calculated for the age groups 0–1, 2–5, 6–9 and 10–14 years. Poisson regression was used to estimate trends of prescription rates by age group and antibiotic subgroup. Results Overall, the age-standardised antibiotic prescription rate decreased significantly by 43% from 746 prescriptions per 1,000 persons in 2010 to 428 per 1,000 in 2018 (p < 0.001). Reductions were most pronounced in the age groups 0–1 year (−50%) and 2–5 years (−44%). The age group 2–5 years exhibited the highest prescription rate with 683 per 1,000 in 2018 (0–1 year: 320/1,000; 6–9 years: 417/1,000; 10–14 years: 273/1,000). Cephalosporins (second and third generation) accounted for 32% of prescribed antibiotics. Conclusions Marked reductions in antibiotic prescribing during the last decade indicate a change towards more judicious paediatric prescribing habits. Compared with other European countries, however, prescribing of second- and third-generation cephalosporins remains high in Germany, suggesting frequent first-line use of these substances for common respiratory infections. Considerable regional variations underline the need for regionally targeted interventions.