Ruddy, Kathryn J.

AbstractObjectiveUsing a large prospective cohort of women age 40 or younger diagnosed with breast cancer, we examined the relationship between perceived partner support and anxiety.MethodsSix hundred seventy‐five young women with breast cancer Stages I–III, median age 36, completed a self‐report baseline questionnaire. Perceived partner support was assessed using items extracted from the marital subscale of the Cancer Rehabilitation Evaluation System; generalized social support was assessed with the Medical Outcomes Study–Social Support Survey. Anxiety was measured using the anxiety subscale of the Hospital Anxiety and Depression Scale. Multivariable logistic regression analyses evaluated the association between partner support, other sociodemographic factors, and anxiety.ResultsMean age at diagnosis was 35.4 years. Fourteen percent of the women were not partnered, and among those who were partnered or in a significant relationship, 20% were categorized as unsupported. In univariate and multivariable analysis adjusting for sociodemographic factors, women in an unsupported‐partnered relationship had higher odds of anxiety symptoms compared with women in a supported‐partnered relationship. Young age and being financially insecure were also both independently associated with anxiety.ConclusionsOur findings suggest that partner support may play a key role in a young woman's adjustment to a serious stressor such as breast cancer. In addition, younger age increases vulnerability to anxiety as does struggling with finances. Because supportive efforts of a partner have potential to protect against the impact of stress, interventions to enhance partner support and reduce anxiety might be beneficial to address challenges experienced as a couple in this setting. Copyright © 2015 John Wiley & Sons, Ltd.

ObjectiveMutations in Charcot–Marie–Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy. Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy—considered “acquired” in medical parlance—is unknown. Chemotherapy‐induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as a clinical model to investigate the association of non‐CMT polyneuropathy with CMT genes.MethodsA total of 269 neurologically asymptomatic cancer patients were enrolled in the clinical trial Alliance N08C1 to receive the neurotoxic drug paclitaxel, while undergoing prospective assessments for polyneuropathy. Forty‐nine CMT genes were analyzed by targeted massively parallel sequencing of genomic DNA from patient blood.ResultsA total of 119 (of 269) patients were identified from the 2 ends of the polyneuropathy phenotype distribution: patients that were most and least susceptible to paclitaxel polyneuropathy. The CMT gene PRX was found to be deleteriously mutated in patients who were susceptible to CIPN but not in controls (p = 8 × 10−3). Genetic variation in another CMT gene, ARHGEF10, was highly significantly associated with CIPN (p = 5 × 10−4). Three nonsynonymous recurrent single nucleotide variants contributed to the ARHGEF10 signal: rs9657362, rs2294039, and rs17683288. Of these, rs9657362 had the strongest effect (odds ratio = 4.8, p = 4 × 10−4).InterpretationThe results reveal an association of CMT gene allelic variability with susceptibility to CIPN. The findings raise the possibility that other acquired polyneuropathies may also be codetermined by genetic etiological factors, of which some may be related to genes already known to cause the phenotypically related Mendelian disorders of CMT. Ann Neurol 2014;76:727–737