Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.Daniel D. Buchanan, Kevin Sweet, Musa Drini, Mark A. Jenkins, Aung Ko Win, Dallas R. English, Michael D. Walsh, Mark Clendenning, Diane M. McKeone, Rhiannon J. Walters, Aedan Roberts, Sally-Ann Pearson, Erika Pavluk, John L. Hopper, Michael R. Gattas, Jack Goldblatt, Jill George, Graeme K. Suthers, Kerry D. Phillips, Sonja Woodal, Julie Arnold, Kathy Tucker, Amanda Muir, Michael Field, Sian Greening, Steven Gallinger, Renee Perrier, John A. Baron, John D. Potter, Robert Haile, Wendy Franke, Albert de la Chapelle, Finlay Macrae, Christophe Rosty, Neal I. Walker, Susan Parry and Joanne P. Youn

Risk of hospitalization and death due to bone fractures after breast cancer: a registry-based cohort study

BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. RESULTS: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index 1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.Swedish Research CouncilSwedish Cancer SocietyFORTEAccepte

Effect of gabapentin on anxiety among 306 breast cancer patients: A URCC CCOP study

Background: Anxiety is prevalent among 18%-77% of cancer patients and is associated with increased insomnia, depression, fatigue and reduced quality of life. In a previous study, we found that gabapentin is effective in reducing hot flashes among cancer patients. Gabapentin is used for treatment of anxiety disorders but there is little scientific evidence supporting its use. The aim of this secondary data analysis is to examine the effect of gabapentin on anxiety. Methods: 420 breast cancer patients experiencing ≥ 2 hot flashes a day were randomized to placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day for 8 weeks (wks). Anxiety was measured by the State-Trait Anxiety Inventory (STAI) at baseline, 4 and 8 wks. Results: At 4 wks, patients (n = 334) receiving gabapentin 300mg reported a reduction in anxiety (change score [CS] = -2.08, standard error [SE] = 0.89) while patients receiving gabapentin 900mg and placebo reported an increase in anxiety (900 mg CS = +0.32, SE = 0.87, placebo CS = +1.01, SE = 0.76). At 8 wks, patients (n = 306) receiving gabapentin 300mg reported a further reduction in anxiety (CS = -2.65, SE = 0.86) while patients receiving gabapentin 900mg and placebo continued to reported increases in anxiety (900 mg CS = +0.16, SE = 1.03, placebo CS = +1.89, SE = 0.97). ANCOVAs controlling for baseline anxiety revealed significantly lower anxiety at 4 and 8 wks among patients receiving gabapentin 300 mg compared to patients receiving placebo (all p \u3c 0.05) with no significant differences between patients receiving gabapentin 900 mg and those receiving placebo. ANCOVAs also showed a significant baseline by treatment interaction at 4 wks (p \u3c 0.05); where patients with higher baseline anxiety reported the greatest reductions in anxiety, but this interaction effect was not present at 8 wks. Conclusions: Gabapentin administered at 300 mg/day is useful in reducing anxiety experienced by breast cancer patients and may be particularly useful for patients experiencing high levels of anxiety short-term. The 300 mg dose may be more effective compared to the 900 mg dose due to an anxiety receptor-specific physiological effect and/or the combination of fewer drug-related toxicities resulting from the lower dose. Funding: U10CA37420 and K07CA132916. No significant financial relationships to disclose

Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer

Oxana Palesh,1 Luke Peppone,2 Pasquale F Innominato,3–5 Michelle Janelsins,2 Monica Jeong,1 Lisa Sprod,7 Josee Savard,6 Max Rotatori,1 Shelli Kesler,1 Melinda Telli,1 Karen Mustian21Stanford University School of Medicine, Stanford, CA, USA; 2University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 3INSERM, UMRS 776, Biological Rhythms and Cancers, Villejuif, France; 4Faculty of Medicine, Universite Paris Sud, le Kremlin-Bicêtre, France; 5APHP, Chronotherapy Unit, Department of Oncology, Paul Brousse Hospital, Villejuif, France; 6Laval University, Quebec, Canada; 7University of North Carolina, Wilmington, NC, USAAbstract: Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.Keywords: cancer, sleep, chemotherapy, intervention, circadian rhythm, cognitive behavioral therap