ABSTRACT
PROBLEM: Human papillomavirus infection is integral to developing invasive cervical cancer in the majority of patients. In a recent genome-wide association study, rs9357152 and rs4243652 have been associated with seropositivity for HPV16 or HPV18, respectively. It is unknown whether these variants also associate with cervical cancer triggered by either HPV16 or HPV18. METHODS: We investigate whether the two HPV susceptibility variants show association with type-specific cervical cancer in a genetic case-control study with cases stratified by HPV16 or HPV18, respectively. We further tested whether rs9357152 modulates gene expression of any of 36 genes at the human leukocyte antigen locus in 256 cervical tissues. RESULTS: rs9357152 was associated with invasive HPV16-positive cervical cancer (OR 1.33, 95%CI 1.03-1.70, p = 0.03), and rs4243652 was associated with HPV18-positive adenocarcinomas (OR 2.96, 95%CI 1.18-7.41, p = 0.02). These associations remained borderline significant after testing against different sets of controls. rs9357152 was found to be an eQTL for HLA-DRB1 in HPV-positive cervical tissues (pANOVA = 0.0009), with the risk allele lowering mRNA levels. CONCLUSIONS: We find evidence that HPV seropositivity variants at chromosome 6 and 14 may modulate type-specific cervical cancer risk. rs9357152 may exert its effect through regulating HLA-DRB1 induction in the presence of HPV. In regard of multiple testing, these results need to be confirmed in larger studies.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/genetics , HLA-DRB1 Chains/genetics , Papillomavirus Infections/complications , Case-Control Studies , Genome-Wide Association Study , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , GenomicsABSTRACT
BACKGROUND: National and international literature and our own preliminary work indicate that the professional integration of migrant doctors in rehabilitation clinics poses a considerable challenge. METHOD: The STIR project worked with four rehabilitation clinics in Germany to develop various measures to ensure the structured transition and professional integration of migrated doctors. The selected measures include a short film, a website, management training, intercultural training, a peer support programme and a strategy for initial discussions. In this article we describe the preparation, implementation and evaluation of the prototypes of the above measures as part of a feasibility study with regard to acceptance, practicability and integrability. OUTCOME: It turns out that the measures can be easily implemented in everyday clinical practice and are accepted and considered useful by the participants. Options for optimisation are described. CONCLUSION: The study provides initial indications of interventions which promote the professional integration of migrated doctors. Additional analyses of sustainability and precise customisation to the local target group are recommended.
