Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk and survival from head and neck cancer

Heavy drinking of alcoholic beverages increases risk of developing squamous cell carcinoma of the head and neck (SCCHN; oral, pharyngeal and laryngeal cancer). This study hypothesized that genetic variation in the ethanol metabolism and oxidative stress pathways may influence the occurrence of and survival from SCCHN. Interview and genotyping data were obtained from 1227 SCCHN cases and 1325 controls from the Carolina Head and Neck Cancer Epidemiology study, a population-based case-control study of head and neck cancer conducted in North Carolina from 2002-2006. Vital status through 2008 was obtained from the National Death Index. A panel of 45 single nucleotide polymorphisms (SNPs) in the ethanol and 19 SNPs in the oxidative stress metabolism pathways were evaluated in relation to the risk of SCCHN using logistic regression and in relation to all-cause and cancer-specific survival using Cox regression. Bonferroni- corrected p-values were also estimated. Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A allele [odds ratio (OR)=0.7, 95% confidence interval (CI)=0.6-0.9)] and ALDH2 rs2238151 C allele (OR=1.2, 95% CI=1.1-1.4). Three SNPs were associated with cancer risk in anatomic sub-sites: ADH1B rs17028834 C allele (larynx, OR=1.5, 95% CI=1.1-2.0), SOD2 rs4342445 A allele (oral cavity, OR=1.3, 95% CI=1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR=2.1, 95% CI=1.2-3.7). Four SNPs in alcohol metabolism genes interacted with level of alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and CYP2E1 rs2249695. No interactions with alcohol were found for oxidative stress pathway SNPs. Minor alleles of two SNPs in CYP2E1 - the C allele of both rs3813865 and rs8192772 - were associated with increased hazard of cancer-specific death [hazard ratio (HR)=2.09, 95%CI=1.38-3.18; HR=1.71, 95% CI=1.23-2.37, respectively]. No associations with survival were found for SNPs in ADH1B, ADH1C, ADH4, ADH7, ALDH2, GPx2, GPx4, and CAT. Previously unreported associations of SNPs in ALDH2, CYP2E1, GPX2, SOD1, and SOD2 with tumor incidence, and in CYP2E1 with cancer-specific survival, warrant further investigation. Associations with cancer incidence provide evidence that genetic variation in alcohol and oxidative stress pathways influence SCCHN carcinogenesis.Doctor of Philosoph

Spaceflight and immune responses of rhesus monkeys

The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses

Movement Limitation and Immune Responses of Rhesus Monkeys

The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-alpha (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CDB+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses

Emergency Department Visits by Patients with Mental Health Disorders — North Carolina, 2008–2010

Patients with mental health disorders (MHDs) use the emergency department (ED) for acute psychiatric emergencies, for injuries and illnesses complicated by or related to their MHD, or when psychiatric or primary-care options are inaccessible or unavailable. An estimated 5% of ambulatory-care visits in the United States during 2007-2008 were made by patients with primary mental health diagnoses. To measure the incidence of ED visits in North Carolina with MHD diagnostic codes (MHD-DCs), the Carolina Center for Health Informatics (University of North Carolina at Chapel Hill) analyzed ED visits occurring during the period 2008-2010 captured by the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT). This report describes the results of that analysis, which indicated that nearly 10% of ED visits had one or more MHD-DCs assigned to the visit and the rate of MHD-DC-related ED visits increased seven times as much as the overall rate of ED visits in North Carolina during the study period. Those with an MHD-DC were admitted to the hospital from the ED more than twice as often as those without MHD-DCs. Stress, anxiety, and depression were diagnosed in 61% of MHD-DC-related ED visits. The annual rate of MHD-DC-related ED visits for those aged ≥65 years was nearly twice the rate of those aged 25-64 years; half of those aged ≥65 years with MHD-DCs were admitted to the hospital from the ED. Mental health is an important component of public health (4). Surveillance is needed to describe trends in ED use for MHDs to develop strategies to prevent hospitalization, improve access to ambulatory care, and develop new ways to provide ED care for the elderly with MHDs

Joint Effects of Alcohol Consumption and Polymorphisms in Alcohol and Oxidative Stress Metabolism Genes on Risk of Head and Neck Cancer

Single nucleotide polymorphisms (SNPs) in alcohol metabolism genes are associated with squamous cell carcinoma of the head and neck (SCCHN), and may influence cancer risk in conjunction with alcohol. Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence

Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer

Heavy alcohol consumption increases risk of developing squamous cell carcinoma of the head and neck (SCCHN). Alcohol metabolism to cytotoxic and mutagenic intermediates acetaldehyde and reactive oxygen species is critical for alcohol-drinking-associated carcinogenesis. We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems