Medicine & Health

Publication Search Results

Now showing 1 - 10 of 96
  • (2009) Packham, Deborah; Ward, Robyn L; Lin, Vita Ap; Hawkins, Nicholas J; Hitchins, Megan P
    Journal Article
    Abstract: Activating mutations of the BRAF and KRAS genes cause constitutive stimulation of an important cell-signaling pathway promoting tumorigenesis, and are increasingly recognized as determinants of response to targeted cancer therapies. The V600E mutation accounts for most of the BRAF mutations in cancer, and KRAS mutations are predominantly encoded by nucleotide substitutions within codons 12 and 13. We designed novel pyrosequencing assays for the detection of the common ‘‘hotspot’’ mutations in these genes, which demonstrated analytical sensitivities of Z10% in titrations of mutant cell AQ1 lines. The KRAS pyrosequencing assay has the ability to simultaneously identify all potential nucleotide changes within the mutation cluster at codons 12 and 13, with a sequence output in the sense direction to facilitate results interpretation. These assays were used to determine the mutation status in a prospective series of 1198 sporadic colorectal cancers. The BRAF V600E mutation was detected in 13.2% of the colorectal cancers. The frequency of KRAS mutations in our cohort was 32.4%, with G>A transitions at position 2 of codons 12 and 13 being most prevalent. Both assays proved highly sensitive and specific when applied to clinical specimens, and were applicable to both fresh-frozen and formalin-fixed paraffin-embedded archival tissues. These assays would serve as a suitable platform for large-scale mutation detection in cancer specimens where the facility for pyrosequencing is available.

  • (2003) Welsh, John; Sapinoso, Lisa; Kern, Suzanne; Brown, David; Liu, Tao; Bauskin, Asne; Ward, Robyn; Hawkins, Nicholas; Quinn, David; Russell, Pamela; Sutherland, Robert; Breit, Samuel; Moskaluk, Christopher; Frierson Jr, Henry; Hampton, Garret
    Journal Article
    Genetic alterations in tumor cells often lead to the emergence of growth-stimulatory autocrine and paracrine signals, involving overexpression of secreted peptide growth factors, cytokines, and hormones. Increased levels of these soluble proteins may be exploited for cancer diagnosis and management or as points of therapeutic intervention. Here, we combined the use of controlled vocabulary terms and sequence-based algorithms to predict genes encoding secreted proteins from among ≈12,500 sequences represented on oligonucleotide microarrays. Expression of these genes was queried in 150 carcinomas from 10 anatomic sites of origin and compared with 46 normal tissues derived from the corresponding sites of tumor origin and other body tissues and organs. Of 74 different genes identified as overexpressed in cancer tissues, several encode proteins with demonstrated clinical diagnostic application, such as α-fetoprotein in liver carcinoma, and kallikreins 6 and 10 in ovarian cancer, or therapeutic utility, such as gastrin-releasing peptide/bombesin in lung carcinomas. We show that several of the other candidate genes encode proteins with high levels of tumor-associated expression by immunohistochemistry on tissue microarrays and further demonstrate significantly elevated levels of another novel candidate protein, macrophage inhibitory cytokine 1, a distant member of the tranforming growth factor-β superfamily, in the serum of patients with metastatic prostate, breast, and colorectal carcinomas. Our results suggest that the combination of annotation/protein sequence analysis, transcript profiling, immunohistochemistry, and immunoassay is a powerful approach for delineating candidate biomarkers with potential clinical significance and may be broadly applicable to other human diseases.

  • (2008) Zwar, N; Richmond, Robyn; Harris, Michael
    Journal Article
    Background: This article examines the prevalence of smoking among general practice patients and assesses their stage of readiness to quit. Method: Descriptive study involving eight general practice registrars working in teaching practices in metropolitan Sydney (New South Wales) who surveyed 1069 consecutive patients over 16 years of age to determine their smoking status; and for smokers, their stage of readiness to stop smoking. Results: Of these patients 375 (35%) were current smokers, with smoking more common among men (40%) than women (33%). Proportions of smokers in each stage of change were: 137 in precontemplation (36.5%), 158 in contemplation (42%) and 79 in preparation (21%). The majority of patients in preparation (67%) and contemplation (53%) were assessed as willing to further discuss their smoking, whereas only 16% of those in the contemplation stage were willing. Discussion: Smoking rates among general practice patients were higher than in community samples. Most of the smokers were either contemplating or preparing to quit, and the majority of smokers in these groups were willing to receive advice about smoking cessation.

  • (2008) Wakefield, Claire; Meiser, Bettina; Gaff, C; Barratt, Anthony; Patel, Minoo; Suthers, G; Lobb, Elizabeth; Ramsay, J; Mann, G
    Journal Article
    Purpose: Despite the established importance of the role of family history in prostate cancer, relatively little research encompasses the psychosocial issues relevant to unaffected men with a family history of prostate cancer. To determine the completeness and quality of available literature on the issues faced by men with a high risk of prostate cancer, we conducted a multidisciplinary review of the literature to provide some guidance on the information that clinicians might provide to men who are concerned about family history. Materials and Methods: A structured literature search was conducted by a multidisciplinary team of clinicians and researchers who reviewed the medical and psychosocial literature, and identified 21 relevant studies. Results: Research suggests that many high risk patients are concerned about the risk of prostate cancer, and some may significantly overestimate that risk. Several studies have shown high screening rates among high risk patients and high levels of interest in genetic testing for prostate cancer risk should it become available, yet many men also report a desire for more information about their personal risk and risk management options. Conclusions: Given the lack of clear data on the efficacy of prostate cancer screening among high risk patients, clinicians could consider providing men who are concerned about family history with information on their personal risk, help them to clarify the potential benefits, limitations and harms of prostate cancer screening in their situation, and then support their choice regarding the management of prostate cancer risk.

  • (2008) Wakefield, Claire; Meiser, Bettina; Homewood, J; Peate, Michelle; Taylor, Adrian; Lobb, Elizabeth; Kirk, J; Young, Mark; Williams, Robyn; Dudding, T; Tucker, Katherine
    Journal Article
    Purpose To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. Methods A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. Results While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). Conclusions Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn.

  • (2008) Cowan, Ruth; Meiser, Bettina; Giles, Graham; Lindeman, Geoffrey; Gaff, Clara
    Journal Article
    Purpose: Genetic testing for hereditary cancer facilitates medical management and improves health outcomes. Genetic testing is not currently available for prostate cancer, but trials are underway to investigate if antiandrogens and selenium have a preventive role for at-risk individuals. To inform future genetic counseling, we sought to understand the pre-existing beliefs and behaviors of men with a family history of prostate cancer and explore their intention to adopt possible preventive behaviors in response to test results. Methods: A survey was completed by 280 men (response: 59%). Results: The belief that diet influenced prostate cancer risk was held by 73% of participants, whereas 37% believed in medication/natural therapies. Thirty-nine percent reported at least one change to their diet, alcohol consumption, smoking, exercise patterns, vitamin/mineral/supplement intake and/or medication/natural therapy in response to their family history. The men expressed interest in genetic testing with 92% `definitely` or `probably` interested. Definite interest was associated with number of affected relatives and prostate cancer-related anxiety. A positive genetic test would motivate 93% of men to make at least one behavioral change. Conclusions: Participants commonly believed behavioral factors influenced prostate cancer risk and reported that they would alter their behavior to reduce risk after (hypothetical) genetic testing.

  • (2008) Kasparian, Nadine; Meiser, Bettina; Butow, P; Simpson, John; Mann, G
    Journal Article
    Despite rapid advancements in molecular genetics research, little is known about the psychological experiences of individuals with a family history of melanoma. The present study aimed to identify factors contributing to psychological distress among affected and unaffected individuals with a strong family history of melanoma. A total of 121 adults who had recently been informed of the identification of a family-specific mutation in the CDKN2A melanoma susceptibility gene, completed a self-report questionnaire assessing cancer-specific and generalized distress, and a variety of potential predictors. Having a personal history of melanoma (OR = 3.37, p = 0.033), perceiving greater family implications of melanoma (OR = 2.52, p < 0.0001), and the tendency to monitor for threatening information (OR = 3.12, p = 0.008) were associated with melanoma-specific distress. Being childless (beta = 2.09, p = 0.007), perceiving sun exposure as an important cause of melanoma (beta = 1.15, p = 0.015), and perceiving greater family implications of melanoma (beta = 1.02, p = 0.002) were associated with greater generalized anxiety, while monitoring moderated the relationship between endorsement of a genetic model of melanoma and generalized anxiety (p = 0.005). As in other common familial cancers, distress was relatively uncommon in this familial melanoma cohort, even after notification of the presence of a family mutation. Participants do not contemplate their melanoma risk in isolation, but evaluate their risk vis-a-vis the experiences of their relatives.

  • (2008) Nagle, C; Lewis, Sharon; Meiser, Bettina; Gunn, J; Halliday, Jane; Bell, Robin
    Journal Article
    Background: Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs) are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods: A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results: Six themes were identified and classified as `intrinsic` if they occurred within the context of the consultation or `extrinsic` if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs` attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs` attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion: The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs` role in facilitating wom

  • (2008) Meiser, Bettina; Kasparian, Nadine; Mitchell, Penny; Strong, Kathryn; Simpson, John; Tabassum, Laila; Mireskandari, Shab; Schofield, Peter
    Journal Article
    Objectives: This study assesses interest in genetic testing for gene variations associated with bipolar disorder and associated information needs. Methods: Two hundred individuals (95 unaffected and 105 affected with either bipolar disorder, schizoaffective disorder-manic type, or recurrent major depression) from families with multiple cases of bipolar disorder were assessed, using mailed, self-administered questionnaires. Results: The percentage of participants reporting interest in genetic testing was associated with the degree of certainty with which any test would indicate the development of bipolar disorder. Interest in genetic testing, given a 25% lifetime risk scenario, was lowest (with 77% of participants indicating interest), and highest for the 100% lifetime risk scenario (92%). Eighty percent of participants indicated interest in genetic testing of their own children; of these 30% reported wanting their children tested at birth, and 33% in early childhood. Forty-one percent of participants reported that they would be interested in preimplantation genetic diagnosis, and 54% in prenatal testing. Limitations: The possibility of ascertainment bias cannot be ruled out. Interest in hypothetical genetic testing for bipolar disorder may not necessarily translate into actual utilization. Conclusions: These results indicate that uptake of genetic testing for genotyping for low-risk alleles related to bipolar disorder is likely to be lower than for testing for high-penetrance gene mutations that follow Mendelian inheritance. The discrepancy between the desired age of testing children and the accepted current practice may be a source of distress and conflict for parents and health professionals alike.

  • (2007) Kasparian, Nadine; Wakefield, Claire; Meiser, Bettina
    Journal Article
    The aim of the present paper was to describe and evaluate many of the measurement scales currently used in genetic counseling outcomes research. A team of three researchers reviewed the available literature and selected a variety of validated instruments suitable for measurement of genetic counseling outcomes. There are numerous scales to assess each of the following outcomes among counselees: satisfaction with genetic counseling; knowledge; decision-making; psychological adjustment; coping; perceived personal control; perceptions of disease risk; and family communication about genetic risk. However, the strengths and limitations inherent to each instrument warrant careful consideration prior to implementation. In the genetic counseling context, scale selection should be undertaken with thought directed towards the characteristics of the research sample (e.g. levels of literacy, culture, medical condition), the practicalities of the research setting (e.g. available funding and resources, time restrictions, researcher expertise), the purpose of the research (i.e. the specific aspect of the genetic counseling experience to be studied), and the science underlying the scale (e.g. theoretical framework, psychometric properties).