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Biomedical subjects

David M Purdie

Publications and source records attributed to David M Purdie.

At least 55 records · Page 3Linked to original sources

ask for it: development of a health advocacy intervention for adults with intellectual disability and their general practitioners.

Two per cent of people in Australia have intellectual disability and the adults in this population often have poor health status. This poor health can be partly attributed to communication difficulties encountered by people with intellectual disability and also health professionals in consultation settings. The design and development processes of an educational intervention to improve communication between patients, general practitioners (GPs) and also advocates in a population of adults with intellectual disability are described. The design process was collaborative and involved adults with intellectual disability, GPs, parents, support workers and other professionals. It was a nine-step development process and led to the final communication tool package, the ask (advocacy skills kit) 5-year health diary and educational session. As a result of the collaborative design and development processes, this diary included qualities not found in most other medical record keeping systems: visual appeal, advice on how to be a health advocate, utility for a range of users, privacy, portability and sufficient capacity to record personal patient information which enhanced communication between doctor, patient and advocate. It is proving to be very popular. Clear implications were found for applying established criteria and incorporating the needs of users in the design of educational interventions in the intellectually disabled population. Health promotion tools aiming to improve the current poor health status of adults with intellectual disability should be developed further.

Adult↗

Hospital-based case-control study of bronchiectasis in indigenous children in Central Australia.

BACKGROUND: Childhood pneumonia has been reported to be associated with the development of bronchiectasis but there are no case-control studies that have examined this. This study examined the relationship between hospital admission for episode(s) of pneumonia and the risk of radiologically proven bronchiectasis. METHODS: A medical record-based case-control study of bronchiectasis in Indigenous children was conducted in Central Australia. Controls (183), matched to cases (61) by gender, age and year of diagnosis, were Indigenous children hospitalized with other conditions. RESULTS: There was a strong association between a history of hospitalized pneumonia and bronchiectasis [odds ratio (OR), 15.2; 95% confidence interval (95% CI) 4.4-52.7]. This was particularly evident in recurrent hospitalized pneumonia (P for trend < 0.01), severe pneumonia episodes with longer hospital stay (P for trend < 0.01), presence of atelectasis (OR 11.9; 95% CI 3.1-45.9) and requirement for oxygen (P for trend < 0.01). The overall number of pneumonia episodes, rather than its site, was associated with bronchiectasis. Although the total number of pneumonia episodes in the first year of life did not increase the risk of bronchiectasis, more severe episodes early in life did. Malnutrition, premature birth and being small for gestational age were more common findings among cases. Breast-feeding appeared to be a protective factor (OR 0.2; 95% CI 0.1-0.7). CONCLUSIONS: Although we cannot fully answer the question of why bronchiectasis is much more common in Indigenous children, we have provided strong evidence of an association between bronchiectasis and severe and recurrent pneumonia episodes in infancy and childhood.

Adolescent↗

Corticosteroid therapy in an alphaviral arthritis.

BACKGROUND: : Corticosteroid use during acute viral arthritis is considered to be contraindicated as a result of the risk of immunosuppression causing enhanced infection and disease exacerbation. OBJECTIVES: : The objective of this study was to analyze the effect of oral corticosteroid therapy on symptoms of the viral arthritic disease, Ross River virus disease (RRVD). METHODS: : Patients with RRVD were enrolled in 2 prospective longitudinal studies. Medications and comorbidities were recorded and the patients' health was assessed using 2 validated quality-of life-questionnaires, the Comparison of Clinical Health Assessment Questionnaire (CLINHAQ) and the Medical Outcomes Study Short Form (SF-36). RESULTS: : Six patients taking corticosteroids showed no exacerbation of RRVD compared with patients not taking steroids. The CLINHAQ Functional Disability Index also indicated that corticosteroid users recovered faster compared with patients using nonsteroidal antiinflammatory drugs. CONCLUSION: : Conventional concern that corticosteroid treatment will exacerbate disease appears unjustified for alphaviral arthritides once serodiagnosis has demonstrated antiviral immunity.

Journal Article↗

Risk of injury from acute alcohol consumption and the influence of confounders.

AIM: To quantify the relationship between acute alcohol consumption and risk of injury, in the context of other potential confounding factors (i.e. usual alcohol intake, risk-taking behaviour and substance use-defined as prescription/over-the-counter medication or illicit substances), using three separate measures of alcohol consumption. DESIGN: A hospital-based, case-control study. SETTING: The accident and emergency department at a large metropolitan teaching hospital in Queensland, Australia. PARTICIPANTS: Four hundred and eighty-eight cases were matched to 488 population controls on gender, age group, neighbourhood, day and time of injury. MEASUREMENTS: Risk factor and injury information was obtained by questionnaire and medical record review. RESULTS: After controlling for demographic and situational variables (i.e. activity, location and companions at time of injury), consuming any alcohol in the 6 hours prior to time of injury significantly increased risk of injury [odds ratio (OR) = 2.13, 95% confidence interval (CI): 1.3-3.9]. Drinking at levels above low-risk guidelines for short-term health (i.e. drinking > 40 g alcohol per occasion if female, and drinking > 60 g alcohol if male) increased injury risk by a factor of almost 2.5 (OR = 2.41; 95% CI = 1.1-5.2). Finally, drinking beer (OR = 1.86; 95% CI = 0.9-3.9), spirits (OR = 3.05; 95% CI = 1.1-8.2) or a combination of beverages (OR = 3.16; 95% CI = 1.1-8.8) increased risk of injury. When usual alcohol consumption patterns were adjusted for, substantial increases in the alcohol-injury odds ratios were observed for all measures of alcohol. When risk-taking behaviour and substance use were considered, changes in the effect of alcohol on injury risk were observed, for all measures of alcohol. These data support the hypotheses that some confounding exists in the alcohol-injury relationship due to usual drinking patterns, risk-taking and substance use. CONCLUSIONS: In this study, acute alcohol consumption significantly increased the risk of injury, even when situational and other risk factors were considered. However, the relationship between alcohol and injury appears confounded by usual drinking patterns, risk-taking behaviour and substance use. Therefore, these variables should be considered in any analysis of the alcohol-injury relationship, and also considered when developing public health strategies to reduce alcohol-related injury. Further research is required to elucidate the nature of this relationship, and to identify the effect of risk-taking and substance use on different types of injuries (e.g. mechanism of injury; body region injured) and injury severity. The stability of the models and the consistency of the findings across all measures of alcohol used support claims for the validity of the observed effects.

Adolescent↗

Medication reviews in the community: results of a randomized, controlled effectiveness trial.

AIMS: To examine the effectiveness of a multidisciplinary service model delivering medication review to patients at risk of medication misadventure in the community. METHODS: The study was carried out in three Australian states; Queensland, New South Wales and Western Australia, and conducted as a randomized, controlled effectiveness trial with the general practitioner (GP) as the unit of randomization. In total, 92 GPs, 53 pharmacists and 400 patients enrolled in the study. The multidisciplinary service model consisted of GP education, patient home visits, pharmacist medication reviews, primary healthcare team conferences, GP implementation of action plans in consultation with patients, and follow-up surgery visits for monitoring. Effectiveness was assessed using the four clinical value compass domains of (i) functional status, (ii) clinical outcomes, (iii) satisfaction and (iv) costs. The domains of functional status (assessed by the health-related quality of life measure SF-36 subscales) and clinical outcomes (as assessed by adverse drug events (ADEs), number of GP visits, hospital services and severity of illness) were measured at baseline and endpoint. Satisfaction was measured by success in implementation and by participant satisfaction at endpoint, and costs (as assessed using medication and healthcare service costs, less intervention costs) were measured preintervention and during the trial. In addition, process evaluation was conducted for intervention patients, in which problems and recommendations from the medication reviews were described. RESULTS: The model was successfully implemented with 92% of intervention GPs suggesting that the model had improved the care of participating patients, a view shared by 94% of pharmacists. In addition, positive trends in clinical outcomes (ADEs and severity of illness) and costs (an ongoing trend towards reduction in healthcare service costs) were evident, although the trial was limited to a 6-month intervention time. No differences between intervention and control groups were identified for the health-related quality of life domain. The cost-effectiveness ratio for the intervention based on cost savings, reduced adverse events and improved health outcomes was small. The most common problems identified in the medication reviews were potential adverse drug reactions, suboptimal monitoring and adherence/lack of concordance issues. In total, 54.4% of recommendations were enacted, and 23.9% were implemented precisely as recommended in the medication review. Follow-up evaluation showed that 70.9% of actions had a positive outcome, 15.7% no effect and 3.7% had a negative outcome. CONCLUSIONS: Most studies emphasize efficacy and the best achievable clinical outcomes rather than whether an intervention will be effective in practice. The current trial showed that three of the four domains in the clinical value compass showed trends of improvement or were indeed improved in the relatively short follow-up period of the trial, suggesting that a service based on this model could achieve similar benefits in practice. A domiciliary medication review programme similar to this model has now been implemented into national Australian practice, where GPs and pharmacists are reimbursed by the Australian government for the provision of these services.

Adult↗

Ross River virus disease in Australia, 1886-1998, with analysis of risk factors associated with outbreaks.

Ross River virus (RR) is a mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand human and environmental factors driving such events, 57 historical reports on RR outbreaks between 1896 and 1998 were examined collectively. The magnitude, regularity, seasonality, and locality of outbreaks were found to be wide ranging; however, analysis of climatic and tidal data highlighted that environmental conditions act differently in tropical, arid, and temperate regions. Overall, rainfall seems to be the single most important risk factor, with over 90% of major outbreak locations receiving higher than average rainfall in preceding months. Many temperatures were close to average, particularly in tropical populations; however, in arid regions, below average maximum temperatures predominated, and in southeast temperate regions, above average minimum temperatures predominated. High spring tides preceded coastal outbreaks, both in the presence and absence of rainfall, and the relationship between rainfall and the Southern Oscillation Index and La Niña episodes suggest they may be useful predictive tools, but only in southeast temperate regions. Such heterogeneity predisposing outbreaks supports the notion that there are different RR epidemiologies throughout Australia but also suggests that generic parameters for the prediction and control of outbreaks are of limited use at a local level.

Alphavirus Infections↗

Differences in climatic factors between Ross River virus disease outbreak and nonoutbreak years.

Ross River virus is a common mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand climatic factors preceding outbreaks, we compared seasonal and monthly rainfall and temperature trends in outbreak and nonoutbreak years at four epidemic-prone locations. Our analyses showed that rainfall in outbreak years tended to be above average and higher than rainfall in nonoutbreak years. Overall temperatures were warmer during outbreak years. However, there were a number of distinct deviations in temperature, which seem to play a role in either promoting or inhibiting outbreaks. These preliminary findings show that climatic differences occur between outbreak and nonoutbreak years; however, seasonal and monthly trends differed across geo-climatic regions of the country. More detailed research is imperative if we are to optimize the surveillance and control of epidemic polyarthritic disease in Australia.

Alphavirus Infections↗

Alcohol, wine, and risk of epithelial ovarian cancer.

Moderate alcohol intake can influence sex hormone levels and affect ovarian function as well as increasing breast cancer risk. This suggests that alcohol might also influence ovarian cancer risk. We have evaluated this among 696 Australian women with histologically confirmed epithelial ovarian cancer and 786 cancer-free control women, selected at random from the electoral roll. Sociodemographic information and a detailed reproductive history were collected in a face-to-face interview, and information about diet and alcohol consumption was obtained from a food frequency questionnaire. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Overall, 59% of women drank <1 standard drink/week and only 5% of cases and 8% of controls drank an average of > or =2 standard drinks/day. Compared with nondrinkers, the OR for women who drank an average of > or =2 standard drinks/day was 0.49 (95% CI = 0.30-0.81). This effect did not vary for the different subtypes but was restricted to wine (OR = 0.56, 95% CI = 0.33-0.93 for > or =1 glass/day versus nondrinkers) with no effect for beer (OR = 1.26, 95% CI = 0.65-2.46) or sherry/spirits (OR = 1.07, 95% CI = 0.59-1.95). Combining our results with the six previous population-based studies gave a pooled OR of 0.72 (95% CI = 0.54-0.97) for the highest alcohol intake group versus nondrinkers. These data suggest that alcohol does not increase risk of ovarian cancer. In this Australian population, the inverse association with alcohol was due solely to wine consumption and so may be a consequence of antioxidants and/or phytoestrogens in wine rather than the alcohol itself.

Adolescent↗

Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Adenocarcinoma, Clear Cell↗

Prevalence and anatomical distribution of naevi in young Queensland children.

Sunlight is the principal environmental cause of melanoma and has also been implicated in the pathogenesis of melanocytic naevi. Epidemiological evidence indicates that childhood is a period during which melanocytes are susceptible to the effects of sunlight, yet little is known about the development of naevi in infancy. We conducted a survey of child-care centres to document the prevalence and anatomical distribution of melanocytic naevi among 193 young children aged 1-3 years in Brisbane, Australia (latitude 27 degrees S). Naevi were counted on all skin surfaces except for the scalp, buttocks and genitalia. Overall, almost 90% of children in the study sample had at least 1 naevus of any size, and more than 30% of children had 10 or more naevi. Total naevus counts ranged from 0 to 45 and were strongly determined by age. When taken together, naevus densities were highest on exposed body sites such as the face and limbs; however the density of large naevi (> or = 5 mm) was significantly higher on the trunk than on the face, neck and ears. These data support the concept that melanocytic neoplasia commences early in life and that naevus evolution is influenced by the anatomical site of the target cell.

Child, Preschool↗

Dietary influences on survival after ovarian cancer.

We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival.

Adult↗

Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma.

BACKGROUND: Some melanomas form on sun-exposed body sites, whereas others do not. We previously proposed that melanomas at different body sites arise through different pathways that have different associations with melanocytic nevi and solar keratoses. We tested this hypothesis in a case-case comparative study of melanoma patients in Queensland, Australia. METHODS: We randomly selected patients from among three prespecified groups reported to the population-based Queensland Cancer Registry: those with superficial spreading or nodular melanomas of the trunk (n = 154, the reference group), those with such melanomas of the head and neck (n = 77, the main comparison group), and those with lentigo maligna melanoma (LMM) (n = 75, the chronic sun-exposed group). Each participant completed a questionnaire, and a research nurse counted melanocytic nevi and solar keratoses. We calculated exposure odds ratios (ORs) and 95% confidence intervals (CIs) to quantify the association between factors of interest and each melanoma group. RESULTS: Patients with head and neck melanomas, compared with patients with melanomas of the trunk, were statistically significantly less likely to have more than 60 nevi (OR = 0.34, 95% CI = 0.15 to 0.79) but were statistically significantly more likely to have more than 20 solar keratoses (OR = 3.61, 95% CI = 1.42 to 9.17) and also tended to have a past history of excised solar skin lesions (OR = 1.87, 95% CI = 0.89 to 3.92). Patients with LMM were also less likely than patients with truncal melanomas to have more than 60 nevi (OR = 0.32, 95% CI = 0.14 to 0.75) and tended toward more solar keratoses (OR = 2.14, 95% CI = 0.88 to 5.16). CONCLUSIONS: Prevalences of nevi and solar keratoses differ markedly between patients with head and neck melanomas or LMM and patients with melanomas of the trunk. Cutaneous melanomas may arise through two pathways, one associated with melanocyte proliferation and the other with chronic exposure to sunlight.

Cell Division↗

Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine.

Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens. It also fails to take advantage of mutated epitopes peculiar to the patient's own tumour, and of CD4+ T lymphocytes as potential effectors of anti-tumour immunity. We therefore sought to determine whether a fully autologous DC vaccine is feasible, and of therapeutic benefit. Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated tumour cells. Of 19 patients enrolled into the trial, sufficient tumour was available to make treatments for 17. Of these, 12 received a complete priming phase of six cycles of either 0.9x10(6) or 5x10(6) DC/intradermal injection, at 2-weekly intervals. Where possible, treatment continued with the lower dose at 6-weekly intervals. The remaining five patients could not complete priming, due to progressive disease. Three of the 12 patients who completed priming have durable complete responses (average duration 35 months+), three had partial responses, and the remaining six had progressive disease (WHO criteria). Disease regression was not correlated with dose or with the development of delayed type hypersensitivity responses to intradermal challenge with irradiated, autologous tumour. However, plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response ( P=0.05) and survival (log rank P<0.001). The treatment had minimal side-effects and was well tolerated by all patients. Mature, monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma, and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses.

Adult↗

Ovulation and risk of epithelial ovarian cancer.

Incessant ovulation is thought to be one of the primary causes of epithelial ovarian cancer. However, the effects of ovulation at different ages and of the various exposures or events that suppress ovulation have not been established. We used data from an Australian case-control study of 791 ovarian cancer cases and 853 controls to examine the effect of ovulation on ovarian cancer risk. The total number of lifetime ovulations was calculated using information provided in a monthly contraceptive/reproductive calendar, as well as incorporating other information such as average menstrual cycle length. An increase of 1 year's worth of ovulation was associated with a 6% increase in risk of ovarian cancer (95% confidence interval [CI] = 4-8%). Ovulations in the 20-29-year age group were associated with the greatest risk, with a 20% increase in risk associated with each year of ovulation during this age period (95% CI = 13-26%). When the effects of different exposures that suppress ovulation were compared, there was an indication that some factors may have a greater effect than others. These findings support the theory that incessant ovulation is a major contributor to the occurrence of ovarian cancer and suggest that ovulations during the 20s may be those most associated with disease risk.

Adult↗

Prime boost vaccination strategies: CD8 T cell numbers, protection, and Th1 bias.

Vaccination strategies involving priming with DNA and boosting with a poxvirus vector have emerged as a preferred combination for the induction of protective CD8 T cell immunity. Using IFN-gamma ELISPOT and a series of DNA plasmid, peptide, and modified vaccinia Ankara (MVA) vaccine combinations, we demonstrate that the DNA/MVA combination was uniquely able to enhance IFN-gamma secretion by Ag-specific CD8 T cells. However, CD8 T cell populations induced by DNA/MVA vaccination failed to show an enhanced capability to mediate protection in an IFN-gamma-independent influenza challenge model. The DNA/MVA vaccine strategy was also not unique in its ability to induce high numbers of CD8 T cells, with optimal strategies simply requiring the use of vaccine modalities that individually induce high numbers of CD8 T cells. These experiments argue that rivals to DNA/poxvirus vaccination strategies for the induction of optimal protective CD8 T cell responses are likely to emerge.

Administration, Intranasal↗

Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis.

BACKGROUND: The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. METHODS: We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. FINDINGS: There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p<0.0001) despite significantly increased iron loading. Similarly, we noted a decrease in Hamp expression in iron-loaded Hfe-knockout mice. Hepatic IREG1 expression was greatly upregulated in patients with haemochromatosis (1.8-fold, 95% CI 1.5-2.2; p=0.002). There was a significant correlation between hepatic iron concentration and expression of HAMP (r=0.59, p=0.02) and IREG1 (r=0.67, p=0.007) in untreated patients. INTERPRETATION: Lack of HAMP upregulation in HFE-associated haemochromatosis despite significant hepatic iron loading indicates that HFE plays an important part in the regulation of hepcidin expression in response to iron overload. Our results imply that the liver is important in the pathophysiology of HFE-associated haemochromatosis. Furthermore, the increase in hepatic IREG1 expression in haemochromatosis suggests that IREG1 could function to facilitate the removal of excess iron from the liver.

Adult↗

BRCA2 Arg372Hispolymorphism and epithelial ovarian cancer risk.

The BRCA2 372 HH genotype defined by the BRCA2 N372H nonconservative amino acid substitution polymorphism was recently reported to be associated with a small increased risk of breast cancer. We investigated whether this polymorphism was associated with ovarian cancer risk by conducting British and Australian case-control comparisons in parallel, including a total sample of 1,121 ovarian cancer cases and 2,643 controls. There was no difference in genotype frequency between control groups from the 2 studies (p = 0.9). The HH genotype was associated with an increased risk of ovarian cancer in both studies, and the risk estimate for the pooled studies was 1.36 (95% CI 1.04-1.77, p = 0.03). There was also a suggestion that this risk may be greater for ovarian cancers of the serous subtype for both studies, with an OR (95% CI) of 1.66 (1.17-2.54) for the 2 studies combined (p = 0.005). The BRCA2 372 HH genotype appears to be associated with an increased risk of ovarian cancer of a similar magnitude to that reported for breast cancer.

Adenocarcinoma, Clear Cell↗