Background: Rab14 regulates endosomal trafficking; however, its binding to Rab11-FIP effectors is a source of conflicting data. Results: Rab14 interacts with the canonical Rab-binding domain of RCP, and both Rab14 and RCP function in neuritogenesis. Conclusion: Rab11-RCP complex formation may precede recruitment of RCP by Rab14. Significance: This study provides a conceptual framework for Rab14 and RCP in health and disease.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA–mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98–1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18–2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

Cancer in adolescents and young adults (AYAs) deserves special consideration for several reasons. AYA cancers encompass paediatric malignancies that present at an older age than expected, or early-onset of cancers that are typically observed in adults. However, disease diagnosed in the AYA population is distinct to those same cancers which are diagnosed in a paediatric or older adult setting. Worse disease-free and overall survival outcomes are observed in the AYA setting, and the incidence of AYA cancers is increasing. Knowledge of an individual’s underlying cancer predisposition can influence their clinical care and may facilitate early tumour surveillance strategies and cascade testing of at-risk relatives. This information can further influence reproductive decision making. In this review we discuss the risk factors contributing to AYA breast cancer, such as heritable predisposition, environmental, and lifestyle factors. We also describe a number of risk models which incorporate genetic factors that aid clinicians in quantifying an individual’s lifetime risk of disease.

Genome-wide association studies have identified novel breast cancer susceptibility loci at 12q24 (rs1292011), 12p11 (rs10771399) and 21q21 (rs2823093). The aim of our study was to investigate the prevalence of variants at these three loci in an Irish sample, and to examine the association between these variants and breast cancer in this cohort. DNA was extracted from the blood or buccal swabs of Irish patients with breast cancer (cases), as well as from healthy Irish female controls. Genotyping was performed for each target using a Taqman-based platform. Data were analysed using IBM Statistical Package for the Social Sciences version 22. Genotyping was performed on samples from 1,267 patients with breast cancer and 841 cancer-free controls. The per-allele odds ratio associated with the minor allele at 12p11 was found to be 0.67 (0.54-0.81, p < 0.001). Genotype-specific odds ratios showed an allele dosage effect with odds ratio of 0.76 (0.6-0.95) for heterozygotes, and 0.23 (0.1-0.51) for rare homozygotes. Minor allele frequencies of the variants at 12q24 and 21q21 did not differ significantly between cases or controls. All three investigated variants were identified in the Irish population. The polymorphism rs10771399 was strongly associated with breast cancer risk in this cohort, and was shown to be associated with reduced odds ratio for all molecular subtypes.

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