Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome).

BACKGROUND: The marked variability in age at onset of colorectal cancer (CRC) in patients with hereditary nonpolyposis colorectal cancer (HNPCC) makes management decisions difficult. Environmental factors governing the phenotypic variability of cancer-associated syndromes such as HNPCC have not been elucidated. METHODS: We determined whether tobacco use would alter CRC risk in carriers of HNPCC-associated mutations, using a retrospective cohort study of germline mutation (hMLH1 or hMSH2) carriers from the Hereditary Cancer Institute at Creighton University, one of the oldest and largest registries of HNPCC patients. The main outcome measure was age at CRC onset, estimated by means of Cox proportional hazards modeling. RESULTS: Tobacco use, hMLH1 mutation carriage (as opposed to hMSH2), and male sex were significantly associated with increased risk of CRC (hazard ratios, 1.43, 2.07, and 1.58, respectively). Alcohol use did not alter CRC risk. CONCLUSIONS: Smoking cessation should be an integral part of HNPCC management. This study underscores the gene x environment interactions in cancer development.

The high prevalence of restless legs syndrome symptoms in liver disease in an academic-based hepatology practice.

STUDY OBJECTIVES: Survey-based epidemiologic studies suggest that restless legs syndrome (RLS) affects approximately 10% of the general population and can cause significantly reduced quality of life due to sleep disturbance. This condition is more prevalent in certain disease states, such as iron deficiency anemia, neuropathy, and renal insufficiency. No such prevalence data exists for RLS in liver disease. The aim of the present project was to assess the self-reported prevalence of RLS using an RLS symptom specific questionnaire in patients presenting to a tertiary hepatology clinic with chronic liver disease (CLD). This was a convenience cohort study of established chronic liver disease patients being seen at a tertiary referral center. A one-page survey querying RLS symptoms was administered in hepatology clinic to patients with chronic liver disease. Restless legs syndrome (RLS) symptoms as agreed upon by the International RLS Study Group were incorporated as 5 key questions. Of 141 completed surveys, 88 were positive yielding a questionnaire based prevalence of RLS of 62% in this select population. RLS risk factors were further assessed through chart review and self-report and using a logistical regression analysis. Comparison between those reporting RLS symptoms and those who did not revealed only self-reported neuropathy to be significantly higher in those with RLS. RLS associated with risk factors accounted much of the total prevalence. Of those with RLS symptoms, 23 surveyed were without known RLS risk factors. This yields a convenience sample prevalence of unexplained RLS symptoms of 16.3% (CI: 10.6-23.5) in this population. There did not appear to be a correlation between the severity of liver dysfunction including the presence of cirrhosis or the etiology and the prevalence of RLS symptoms. Quality of Life (QoL) surveys specific to RLS completed suggest RLS symptoms result in significantly diminished QoL, with an average QoL score of 68 on a 0-100 scale. CONCLUSION: This study is the first investigation of RLS prevalence in liver dysfunction. This select population of medically complex patients who all have some degree of liver dysfunction appear to have a surprisingly high prevalence of RLS symptoms. While much of this prevalence may be the result of known secondary causes further investigation is warranted to explore the relationship between RLS and liver dysfunction.