Bradley E. Aouizerat

Abstract

PURPOSE/OBJECTIVES: To identify subgroups of outpatients with cancer based on their experiences with the symptoms of fatigue, sleep disturbance, depression, and pain; to explore whether patients in the subgroups differed on selected demographic, disease, and treatment characteristics; and to determine whether patients in the subgroups differed on two important patient outcomes: functional status and quality of life (QOL). DESIGN: Descriptive, correlational study. SETTING: Four outpatient oncology practices in northern California. SAMPLE: 191 outpatients with cancer receiving active treatment. METHODS: Patients completed a demographic questionnaire, Karnofsky Performance Status scale, Lee Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies Depression Scale, Multidimensional Quality-of-Life Scale Cancer, and a numeric rating scale of worst pain intensity. Medical records were reviewed for disease and treatment information. Cluster analysis was used to identify patient subgroups based on patients symptom experiences. Differences in demographic, disease, and treatment characteristics as well as in outcomes were evaluated using analysis of variance and chi square analysis. MAIN RESEARCH VARIABLES: Subgroup membership, fatigue, sleep disturbance, depression, pain, functional status, and QOL. FINDINGS: Four relatively distinct patient subgroups were identified based on patients experiences with four highly prevalent and related symptoms. CONCLUSIONS: The subgroup of patients who reported low levels of all four symptoms reported the best functional status and QOL. IMPLICATIONS FOR NURSING: The findings from this study need to be replicated before definitive clinical practice recommendations can be made. Until that time, clinicians need to assess patients for the occurrence of multiple symptoms that may place them at increased risk for poorer outcomes.

Abstract

Purpose/Objectives: To describe knowledge of hereditary, familial, and sporadic breast cancer risk factors among women in the community and to identify characteristics associated with this knowledge. Design: Descriptive, cross-sectional. Setting: Community settings in the San Francisco Bay Area. Sample: 184 women who had never been diagnosed with cancer, were 30-85 years old (X=47 ± 12), and agreed to complete a questionnaire in Engfish. Participants were from diverse racial and cultural backgrounds (i.e., 43% European descent, 27% African descent, 16% Asian descent, and 14% Hispanic descent). Many (49%) were college graduates, and 24% had a median annual family income of $30,000-$50,000. Methods: Survey. Main Research Variables Knowledge of hereditary, familial, and sporadic breast cancer risk factors and characteristics associated with this knowledge. Findings: Although most women recognized heredity as a risk factor, some did not understand the impact of paternal family history on risk. Some women did not recognize the relationship between breast and ovarian cancer, risk factors associated with the Gail model, and that aging increases risk. Education level was the most important characteristic associated with knowledge of risk factors. Conclusions: Although age and family history are independent predictors of sporadic, hereditary, and familial breast cancer risk, women in the community could not distinguish between the three forms of the disease. Although the sample included a large number of educated women, their knowledge of breast cancer risk factors appeared incomplete. Implications for Nursing: Advanced practice nurses should provide Individualized risk assessment and education regarding breast cancer risk factors.

Abstract

Family history is a major risk factor for myocardial infarction (MI). However, known gene variants associated with MI cannot fully explain the genetic component of MI risk. We hypothesized that a gene-centric association study that was not limited to candidate genes could identify novel genetic associations with MI. We studied 11,053 single-nucleotide polymorphisms (SNPs) in 6,891 genes, focusing on SNPs that could influence gene function to increase the likelihood of identifying disease-causing gene variants. To minimize false-positive associations generated by multiple testing, two studies were used to identify a limited number of nominally associated SNPs; a third study tested the hypotheses that these SNPs are associated with MI. In the initial study (of 340 cases and 346 controls), 637 SNPs were associated with MI (P < .05); these were evaluated in a second study (of 445 cases and 606 controls), and 31 of the 637 SNPs were associated with MI (P < .05) and had the same risk allele as in the first study. For each of these 31 SNPs, we tested the hypothesis that it is associated with MI, using a third study (of 560 cases and 891 controls). We found that four of these gene variants were associated with MI (P < .05; false-discovery rate <10%) and had the same risk allele as in the first two studies. These gene variants encode the cytoskeletal protein palladin (KIAA0992 [odds ratio (OR) 1.40]), a tyrosine kinase (ROS1 [OR 1.75]), and two G protein-coupled receptors (TAS2R50 [OR 1.58] and OR13G1 [OR 1.40]); all ORs are for carriers of two versus zero risk alleles. These findings could lead to a better understanding of MI pathophysiology and improved patient risk assessment.

Abstract

Apolipoprotein E (APOE) polymorphism plays an important role in lipid metabolism. Preliminary evidence suggests that APOE genotype appears to be a risk factor for not only cardiovascular disease, but also Alzheimer's disease and cancer. We screened the APOE genotype in 290 breast cancer patients and 232 non-cancer controls and determined the relationship between APOE gene polymorphism and breast cancer in Taiwan. We found risk for breast cancer was associated with the APOE genotype (ξ2 = 8.652, p = 0.013). Carriers of the ε4 allele were more common in breast cancer cases than carriers of ε3 allele (p = 0.004, OR = 1.786, 95% CI: 1.197-2.664). In addition, the ε4 allele is also associated with HER2/neu negative status in breast cancer patients (p = 0.006, OR = 0.277, 95% CI: 0.111-0.693). No significant associations between APOE genotype and tumor grade, TN classification, progesterone receptor, estrogen receptor, lymphatic invasion, or recurrence of breast cancer were in evidence. These results suggest that the APOE ε4 allele may be a risk factor for breast cancer and correlates with HER2/neu negative status.

Abstract

More than 24,000 women in the United States are diagnosed with ovarian cancer every year, and half of these women die from their disease. Stage 1 ovarian cancer is curable in 95% of cases; however, due to inadequate screening tools and lack of symptoms in early disease, ovarian cancer is generally at Stage 3 or 4 when finally diagnosed. CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. When its levels are elevated postsurgery (hysterectomy/salpingo-oophorectomy with or without peritoneal washings and lymph node biopsy) and postchemotherapy, it is suggestive of recurrent disease. Due to its similarly elevated levels in some nonmalignant conditions, however, it is not specific enough to be used for population screening. The CA125 molecule is considered a very large glycoprotein because of its molecular weight, and it has three domains: the carboxy terminal domain, the extracellular domain, and the amino terminal domain. MUC16 is the gene that encodes the peptide moiety of the CA125 molecule. MUC16 domains provide novel opportunities to develop newassays and refine current tools to improve the sensitivity and specificity of CA125 for population-based screening guidelines.

Abstract

HM74 (GPR109B) and the highly homologous gene, HM74A (GPR109A) code for Gi-G protein-coupled orphan receptors that recently have been discovered to be involved in the metabolic effects of niacin. The B vitamin niacin is an important agent used in the treatment of dyslipidemias, but its use is limited by side effects. The novel role of the adjacent HM74 and HM74A genes in the metabolism of niacin may provide new targets for drug development. Human genetic variations in HM74 and HM74A have been reported but have not been studied in detail. These variations may play a role in the response to agents targeting receptors coded by these genes. Here we show that many of the nonsynonymous SNPs listed in public databases for HM74 and HM74A are artifacts resulting from extensive homology between these two genes. This may be representative of a neglected phenomenon in reporting sequences of highly homologous genes. We provide primer sequences that permit selective amplification of the complete coding regions of HM74 and HM74A. Using these primers, we show that subsequent sequencing of HM74 and HM74A reveals a novel and unique variation in the HM74A gene. Haplotype analysis suggests four SNPs can define the five major haplotypes that lie within a single haplotype block encompassing these two genes.