Women's preferences and consultants' communication of risk in consultations about familial breast cancer: impact on patient outcomes.
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Adult↗
Biomedical subjects
K Tucker
Publications and source records attributed to K Tucker.
Tailoring communication in consultations with women from high risk breast cancer families.
This multicentre study examined the influence of patient demographic, disease status and psychological variables on clinical geneticists/genetic counsellors (consultants) behaviours in initial consultations with women from high-risk breast cancer families. One hundred and fifty-eight women completed a pre-clinic self-report questionnaire. The consultations were audiotaped, transcribed verbatim and coded. Consultants did not vary their behaviour according to women's expectations. However, significantly more aspects of genetic testing were discussed with women who were affected with breast cancer (P<0.001), screening and management with unaffected women (P=0.01) and breast cancer prevention with younger women (P=0.01). Prophylactic mastectomy was discussed more frequently with women with medical and allied health training (P=0.02), and prophylactic oophorectomy with women affected with breast cancer (P=0.03), those in non-professional occupations (P=0.04) and with a family history of breast and ovarian cancer (P<0.001). Consultants used significantly more behaviours to facilitate understanding with women who were in non-professional occupations (P=0.04); facilitated active patient involvement more with women affected with breast cancer (P<0.001) and used more supportive and counselling behaviours with affected women (P=0.02). This study showed that patient demographics were more likely to predict consultants' communication behaviours than the woman's psychological status. Methods to facilitate assessment of psychological morbidity are needed to allow more tailored communication.
Adult↗
Neurotrophin modulation of voltage-gated potassium channels in rat through TrkB receptors is time and sensory experience dependent.
The whole-cell configuration of the patch-clamp technique, immunoprecipitation experiments and unilateral naris occlusions were used to investigate whether the voltage-gated potassium channel Kv1.3 was a substrate for neurotrophin-induced tyrosine phosphorylation and subsequent functional modulation of current properties in cultured rat olfactory bulb (OB) neurons. Membrane proteins of the OB included all three Trk receptor kinases, but the truncated form of the receptor, lacking an intact kinase domain, was the predominant form of the protein for TrkA and TrkC, while TrkB was predominantly found as the full-length receptor. Acute (15 min) stimulation of OB neurons with bath application of 50 ng ml(-1) brain-derived neurotrophic factor (BDNF), which is a selective ligand for TrkB, caused suppression of the whole-cell outward current and no changes in the kinetics of inactivation or deactivation. Acute stimulation with either nerve growth factor or neurotrophin-3 failed to evoke any changes in Kv1.3 function in the OB neurons. Chronic exposure to BDNF (days) caused an increase in the magnitude of Kv1.3 current and speeding of the inactivation and deactivation of the channel. Acute BDNF-induced activation of TrkB receptors significantly increased tyrosine phosphorylation of Kv1.3 in the OB, as shown using a combined immunoprecipitation and Western blot analysis. With unilateral naris occlusion, the acute BDNF-induced tyrosine phosphorylation of Kv1.3 was increased in neurons lacking odour sensory experience. In summary, the duration of neurotrophin exposure and the sensory-dependent state of a neuron can influence the degree of phosphorylation of a voltage-gated ion channel and its concomitant functional modulation by neurotrophins.
Amino Acid Sequence↗
Variables in the spread of tumor cells to trocars and port sites during operative laparoscopy.
BACKGROUND: Port-site recurrences have delayed the uptake of laparoscopic colectomy, but the etiology of these is incompletely understood. These studies were designed to investigate variables such as the size of the tumor inoculum and the volume and pressure of the insufflated gas during operative laparoscopy that might affect the deposition of these cells in relation to trocars and port sites. METHODS: Radiolabeled human colon cancer cells were injected into the peritoneal cavity of pigs. Three trocars were inserted, and the abdomen was insufflated with carbon dioxide. The movement of cells within the abdomen was traced on a gamma camera. After 2 h, the trocars were removed and the port sites excised. Two studies were performed. In the first study, tumor inocula were varied from 1.5 x 10(5) to 120 x 10(5). In the second study, insufflation pressure was varied, with pressures 0, 4, 8 and 12 mmHg were studied. RESULTS: When larger tumor inocula were injected, the contamination of both trocars (p = 0.005, Kendall's rank correlation) and trocar sites (p = 0.04, Kendall's rank correlation) increased. The deposition of cells on a trocar site was linked to contamination of its trocar (p = 0.03, chi-square), but the contamination of trocars did not always result in trocar-site contamination (p = 0.5, chi-square). Increased volumes of gas insufflation caused increased intraabdominal movement of tumour cells (p = 0.01, Kendall's rank correlation), although this did not lead to greater contamination of trocars or port sites (p = 0.82, Kendall's rank correlation). Decreased insufflation pressures resulted in increased contamination of trocars and port sites (p = 0.01, Kendall's rank correlation). CONCLUSIONS: If clinical situations parallel this study, strategies such as increasing insufflation pressure, reducing episodes of desufflation and gas leaks, and using frequent intraabdominal lavage may help to reduce the numbers of viable tumor cells displaced to port sites during laparoscopic surgery for intraabdominal malignancy. This may reduce the rate of port-site metastases.
Abdominal Wall↗
The effect of lavage on intraabdominal cell burden.
BACKGROUND: Abdominal lavage is a common surgical practice, but few studies have been conducted to assess its efficacy at removing cells from the abdominal cavity, particularly during laparoscopic surgery. METHODS: After three 12-mm trocars were inserted into six female 30-kg pigs at the umbilicus left and right iliac fossae, the abdomen was insufflated with carbon dioxide. The pelvis of each pigs was injected with 6 million radiolabeled LIM 1215 cells. Then the abdominal cavity was irrigated with either 500 ml 0.9% saline, 500 ml 10% betadine solution, or 1 L 0.9% saline. A maximum of 5 L of solution was used for each animal. The lavage fluid was suctioned into separate containers after each aliquot, and each container was measured for radioactivity. RESULTS: Significantly greater numbers of cells were removed by lavage by the first to third lavage cycle; however, after four lavage cycles, relatively few cells were removed by each further cycle. No difference was observed between 500-ml and 1-L aliquots. Additionally, the mechanical efficacy of 0.9% saline and 10% betadine solution appeared similar. CONCLUSION: These findings suggest that optimal lavage consists of four irrigation/suction cycles utilizing 500-ml aliquots.
Abdomen↗
Psychological impact of prophylactic oophorectomy in women at increased risk of developing ovarian cancer: a prospective study.
OBJECTIVES: The objectives of this study were twofold: to prospectively assess whether expressed intention to undergo prophylactic oophorectomy translated into uptake and to evaluate the psychological impact of the procedure in a sample of unaffected women with a strong family history of breast/ovarian cancer. METHODS: Ninety-five women, initially assessed at the time of their first attendance at a familial cancer clinic, were followed-up 3 years later. A total of 22 women (23.2%) in this study had undergone a prophylactic oophorectomy. Ten women (10.5%) who had undergone a prophylactic oophorectomy during the 3-year follow-up period were compared to 73 women (76.9%) who did not have a prophylactic oophorectomy. Twelve women (12.6%) who had the procedure prior to study entry were also assessed for psychological adjustment and associated information needs. RESULTS: Age emerged as a significant predictor of uptake of prophylactic oophorectomy (chi(2) = 7.13, P = 0.009). Among those who had the procedure after study entry, a significant reduction in ovarian cancer anxiety was observed (Z = -2.19, P = 0.029). Of the 22 women who had undergone a prophylactic oophorectomy in total (both before and after study entry), 86.4% reported a high degree of satisfaction with their decision to have the procedure. A low level of screening uptake was also reported by women who did not have a prophylactic oophorectomy but for whom screening was recommended. CONCLUSION: Findings demonstrate that prophylactic oophorectomy is successful in reducing anxiety about ovarian cancer. The results also suggest that women perceive that the benefit of anxiety reduction may outweigh the potentially adverse effects of the procedure, given that women expressed a high level of satisfaction with their decision.
Adult↗
Psychological impact of genetic testing in women from high-risk breast cancer families.
Psychological adjustment in 90 women (30 carriers and 60 non-carriers) who had undergone genetic testing for mutations in BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes was compared with that of 53 women who were not offered genetic testing. Women were assessed prior to genetic testing and 7-10 days, 4 and 12 months after carrier status disclosure using self-administered questionnaires. Compared with women not offered testing, mutation carriers had significantly higher breast cancer distress 7-10 days (t=2.80, P=0.005) and 12 months (t=2.01, P=0.045) post-notification. Non-carriers showed a significant decrease in state anxiety 7-10 days post-notification (t=2.27, P=0.024) and in depression 4 months post-notification (t=2.26, P=0.024), compared with women not offered testing. These data show that non-carriers derive psychological benefits from genetic testing. Women testing positive may anticipate a sustained increase in breast cancer distress following disclosure, although no other adverse psychological outcomes were observed in this group.
Adult↗
Experimental study of the material composition of laparoscopic ports on tumour cell adherence.
BACKGROUND: Laparoscopic resection of intra-abdominal malignancies has yet to be widely adopted, partly because of concerns over the possible increase in the rate of port-site metastasis. The aetiology of these is unclear, but the laparoscopic instrumentation used may influence the deposition of tumour cells at the port sites during operation. An in vitro model to examine tumour cell adherence to laparoscopic ports and to port sites was developed to examine this hypothesis. METHODS: A pilot study (study 1) was performed in which six smooth plastic, six ribbed plastic and six metal ports were introduced through the shaved abdominal wall of a cadaveric sheep and suspended in a water-bath containing radiolabelled LIM 1215 human colonic cancer cells for 30 min. Radioactivity on both ports and port sites was measured and the number of cells adherent to each structure was calculated. The study was expanded to include a further 36 smooth plastic ports and 36 metal ports (study 2). RESULTS: In study 1 metal ports were found to have significantly more adherent cells than plastic ports (P = 0.004), as did ribbed ports when compared with smooth ports (P < 0.05). In study 2 increased numbers of cells were again detected on metal ports (P < 0.001) when compared with plastic ports. Significantly greater numbers of cells were also detected on the sites through which metal ports had passed than on sites through which plastic ports had passed (P = 0.03). CONCLUSION: In this model, the use of metal ports as opposed to plastic ports resulted in increased deposition of tumour cells on both ports and port sites.
Animals↗
The use of audiotapes in consultations with women from high risk breast cancer families: a randomised trial.
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Adult↗
The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data.
BACKGROUND: Several studies have shown that Ashkenazi Jews in the United States and Israel have a high prevalence of the founder mutations BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT, and APC I1307K at frequencies of 1.0--1.1%, 0.2--0.3%, 0.6--1.4%, and 6.1--7.0%, respectively. The objective of this study was to compare the prevalence of these alleles in the Australian Jewish population with that of U.S. Jews. Australian Jews have a different history of migration, with less opportunity for changes in allele frequency due to conversion or intermarriage with non-Jewish Australians. The results obtained therefore can be used to assess whether U.S. data can be generalized to other Jewish populations. SUBJECTS AND METHODS. Subject samples were ascertained through a screening program for Tay-Sachs disease as part of a community-based screening program in New South Wales and Victoria. DNA extracted from 1200 deidentified blood samples was tested using amplification refractory mutation system polymerase chain reaction. RESULTS: The allele frequencies found were as follows: BRCA1 185delAG 1.25% (95% confidence interval [CI], 0.62--1.88%), BRCA1 5382insC 0.25% (95% CI, 0--0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50--1.67%), and APC I1307K 8.67% (95% CI, 7.07--10.26%). The prevalence of breast carcinoma predisposition alleles therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS: There were no significant differences between the allele frequencies in Australian Ashkenazim and those identified in other studies with similar ascertainment strategies, despite the different migration patterns of Australian Jews. This suggests the broad applicability of the U.S. and Israeli data, not only to Australian Ashkenazim, but also to Ashkenazi communities throughout the world.
Adult↗
Sexual dimorphism and developmental expression of signal-transduction machinery in the vomeronasal organ.
We have explored the use of a new model to study the transduction of chemosignals in the vomeronasal organ (VNO), for which the functional pathway for chemical communication is incompletely understood. Because putative vomeronasal receptors in mammalian and other vertebrate models belong to the superfamily of G-protein-coupled receptors, the objective of the present study was to define which G-protein subunits were present in the VNO of Sternotherus odoratus (stinkpot or musk turtle) in order to provide directionality for future functional studies of the downstream signaling cascades. The turtle vomeronasal epithelium (VNE) was found to contain the G-proteins G(beta) and G(alphail-3) at the microvillar layer, the presumed site of signal tranduction in these neurons, as evidenced by immunocytochemical techniques. G(alphao) labeled the axon bundles in the VNE and the somata of the vomeronasal sensory neurons but not the microvillar layer. Densitometric analysis of Western blots indicated that the VNO from females contained greater concentrations of G(alphai1-3) compared with males. Sexually immature (juvenile) turtles showed intense immunolabeling for all three subunits (G(beta), G(alphai1-3), and G(alphao)) in the axon bundles and an absence of labeling in the microvillar layer. Another putative signaling component found in the microvilli of mammalian VNO, transient receptor potential channel, was also immunoreactive in S. odoratus in a gender-specific manner, as quantified by Western blot analysis. These data demonstrate the utility of Sternotherus for discerning the functional signal transduction machinery in the VNO and may suggest that gender and developmental differences in effector proteins or cellular signaling components may be used to activate sex-specific behaviors.
Aging↗
Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer.
This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up, and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message.
Adaptation, Psychological↗
Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study.
BACKGROUND: The effect of alcohol drinking on LDL-cholesterol concentrations is unclear. The reported variability may be due to interactions between genetic factors and alcohol intake. OBJECTIVE: The purpose of the study was to examine whether variation at the apolipoprotein E gene (APOE) locus modulates the association between alcohol drinking and LDL cholesterol. DESIGN: We used a cross-sectional design in a healthy population-based sample of 1014 men and 1133 women from the Framingham Offspring Study. RESULTS: In male nondrinkers (n = 197), LDL cholesterol was not significantly different across APOE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APOE*E4 (E4)]. However, in male drinkers (n = 817), differences were observed (P: < 0.001); those with the E2 allele had the lowest concentrations. LDL cholesterol in men with the E2 allele was significantly lower in drinkers than in nondrinkers but was significantly higher in drinkers than in nondrinkers in men with the E4 allele. This APOE-alcohol interaction remained significant (P < 0.001) after age, body mass index, smoking status, and fat and energy intakes were controlled for. In women, the expected effect of APOE alleles on LDL cholesterol occurred in both drinkers (n = 791; P < 0.001) and nondrinkers (n = 342; P < 0.001). Multiple linear regression models showed a negative association (P < 0.05) between alcohol and LDL cholesterol in men with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 allele. CONCLUSION: In men, the effects of alcohol intake on LDL cholesterol are modulated in part by variability at the APOE locus.
Adult↗
Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity.
Familial adenomatous polyposis (FAP) is characterised by the presence of profuse colonic carpeting of adenomas throughout the entire colon and rectum. The genetic basis of FAP has been shown to be primarily associated with germline mutations in the APC gene. Notwithstanding, several reports have been published indicating that there is genetic heterogeneity in FAP and that the most likely explanation is the existence of another gene. In this report we further delineate the genotype/phenotype correlation in families that harbour germline mutations in the APC gene and identify some previously unreported changes in the APC gene which predispose to an attenuated disease phenotype. From 53 index patients diagnosed with either FAP or attenuated FAP, 27 harboured changes in the APC gene. The remaining 26 patients were further subgrouped according to their colonic phenotype. There were nine patients with a mixed hyperplastic/adenomatous colonic phenotype and there were 17 patients with an adenomatous colonic phenotype. Evaluation of the disease characteristics of these patients and their families is presented which may aid in the identification of new genes associated with colonic polyposis.
Adenomatous Polyposis Coli↗
Cultural aspects of cancer genetics: setting a research agenda.
BACKGROUND: Anecdotal evidence suggests that people from non-Anglo-Celtic backgrounds are under-represented at familial cancer clinics in the UK, the USA, and Australia. This article discusses cultural beliefs as a potential key barrier to access, reviews previous empirical research on cultural aspects of cancer genetics, draws implications from findings, and sets a research agenda on the inter-relationships between culture, cancer genetics, and kinship. METHODS: The CD-ROM databases MEDLINE, PsychLIT, CINAHL, and Sociological Abstracts were searched from 1980 onwards. RESULTS: Cultural aspects of cancer genetics is the focus of an emerging body of publications. Almost all studies assessed African-American women with a family history of breast cancer and few studies included more diverse samples, such as Americans of Ashkenazi Jewish background or Hawaiian- and Japanese-Americans. Our analysis of published reports suggests several directions for future research. First, an increased focus on various Asian societies appears warranted. Research outside North America could explore the extent to which findings can be replicated in other multicultural settings. In addition, control group designs are likely to benefit from systematically assessing culture based beliefs and cultural identity in the "majority culture" group used for comparative purposes. CONCLUSION: More data on which to base the provision of culturally appropriate familial cancer clinic services to ethnically diverse societies are needed. Empirical data will assist with culturally appropriate categorisation of people from other cultures into risk groups based on their family histories and provide the basis for the development of culturally appropriate patient education strategies and materials.
Black or African American↗
Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds.
Hereditary nonpolyposis colorectal cancer (HNPCC) describes the condition of a disparate group of families that have in common a predisposition to colorectal cancer in the absence of a premalignant phenotype. The genetic basis of this disease has been linked to mutations in genes associated with DNA mismatch repair. A large proportion of families harbor changes in one of two genes, hMSH2 and hMLH1. Approximately 35% of families in which the diagnosis is based on the Amsterdam criteria do not appear to harbor mutations in DNA-mismatch-repair genes. In this report we present data from a large series of families with HNPCC and indicate that there are subtle differences between families that harbor germline changes in hMSH2 and families that harbor hMLH1 mutations. Furthermore, there are differences between the mutation-positive group (hMSH2 and hMLH1 combined) of families and the mutation-negative group of families. The major findings identified in this study focus primarily on the extracolonic disease profile observed between the mutation-positive families and the mutation-negative families. Breast cancer was not significantly overrepresented in the hMSH2 mutation-positive group but was overrepresented in the hMLH1 mutation-positive group and in the mutation-negative group. Prostate cancer was not overrepresented in the mutation-positive groups but was overrepresented in the mutation-negative group. In age at diagnosis of colorectal cancer, there was no difference between the hMSH2 mutation-positive group and the hMLH1 mutation-positive group, but there was a significant difference between these two groups and the mutation-negative group.
Adolescent↗
Breast cancer screening uptake in women at increased risk of developing hereditary breast cancer.
This multicenter study assessed breast cancer screening uptake in 461 unaffected women at increased risk of developing breast cancer on the basis of family history who approached familial cancer clinics for advice about surveillance options. At the time of attending the clinic, 89% and 90% of participants were vigilant with respect to age- and risk-specific recommendations for mammography and clinical breast examination, respectively, and 51% reported practicing breast self-examination monthly or more frequently. The degree to which health outcomes are perceived to be under one's personal control (chi2 = -2.09, p = 0.0037) and breast cancer anxiety (chi2 = 8.11, p = 0.044) were both associated with monthly or more frequent breast self-examination, while there were no associations with sociodemographic characteristics. A significantly lower percentage (56%) of women aged <30 were vigilant with respect to mammography recommendations, compared to 77%, 96% and 98% of women aged 30-39, 40-49 and >50, respectively (chi2 = 37.2, p < 0.0001). These relatively low rates of mammographic screening in young women may reflect concerns about increased cancer risk associated with early and repeated radiation exposure or lack of sensitivity in young women with radiographically dense breasts. If mammographic screening is ultimately shown to lower mortality in women at high risk, there will be a strong case to promote screening in young women. The need for regular mammographic screening would then need to be highlighted and reinforced amongst young women and their referring physicians. Awareness amongst general practitioners, who are largely responsible for referral to screening services, would also need to be increased.
Adolescent↗
Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.
Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.
Adolescent↗