Large genomic alterations in hMSH2 and hMLH1 in early-onset colorectal cancer: identification of a large complex de novo hMLH1 alteration.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Giles.
Explore the source record for details and available documents.
The implementation of the two-week wait initiative for cancer referrals in the NHS has had a major impact on outpatient services. A low clinical detection rate among GPs for neurological cancer has resulted in a large number of urgent referrals with a low yield of positive diagnoses. We have devised a strategy for minimizing the impact on outpatient clinics: patients are scanned prior to clinical review and those with normal scans are referred back to the GP without a clinic appointment. Out of 69 referrals of suspected CNS cancer made in 2003, 61 were scanned and six resulted in a positive diagnosis. The equivalent of 10 clinics was saved, and an increased speed of diagnosis and treatment was achieved with no compromise in patient care. Our study illustrates the consequences of the 2-week wait initiative on the neurosurgical service, and proposes an effective and safe solution.
Explore the source record for details and available documents.
BACKGROUND: The validity and magnitude of an association between myositis and malignant disease continue to be debated. Such issues as the legitimacy of a myositis diagnosis and distinction among myositis subgroups in previous population-based studies remain unresolved. OBJECTIVE: To determine the risk for malignant disease in patients with biopsy-proven inflammatory myopathies. DESIGN: Population-based, retrospective cohort study. SETTING: Victoria, Australia. PATIENTS: 537 patients in whom a biopsy-positive idiopathic inflammatory myopathy was first diagnosed from 1981 through 1995. MEASUREMENTS: Standardized incidence ratios were calculated to compare the incidence of malignant disease in patients with inflammatory myopathy and the general population. RESULTS: A total of 116 cases of malignant disease were found in 104 patients. Seventy-four cases were identified concurrently with (within 7 days) or after diagnosis of myositis. The highest risk for malignant disease was associated with dermatomyositis (standardized incidence ratio, 6.2 [95% CI, 3.9 to 10.0]). The risk was also increased in polymyositis (standardized incidence ratio, 2.0 [CI, 1.4 to 2.7]), although the relative risk for malignant disease in dermatomyositis compared with polymyositis was 2.4 (CI, 1.3 to 4.2). An increased risk for malignant disease was also found in inclusion-body myositis (standardized incidence ratio, 2.4 [CI, 1.2 to 4.9]). The excess risk for malignant disease diminished with time (standardized incidence ratio, 4.4 [CI, 2.7 to 7.1] in the first year; 3.4 [CI, 2.3 to 5.1] between 1 and 3 years; 2.2 [CI, 1.3 to 3.9] between 3 and 5 years; and 1.6 [CI, 1.0 to 2.6] beyond 5 years [ P for trend, 0.002]). CONCLUSION: The risk for malignant disease is increased in biopsy-proven dermatomyositis and polymyositis and also appears to be increased in inclusion-body myositis.
BACKGROUND: All cases of in situ and invasive breast cancer are reported to the Victorian Cancer Registry. In 1988 a special subregister of all cases of carcinoma in situ and small invasive cancers up to 10 mm in size was established--the In situ and Small Invasive Breast Cancer Register (ISSIBCR). This was unique in being a population-based register and only possible because in Victoria, as in some other Australian states, all cancers including in situ disease are reported to the Central Cancer Registry. METHODS: Between 1 January 1988 and 31 December 1992, 517 cases of in situ cancers and 892 invasive cancers of < or =10 mm in diameter were registered. During the study period, mammography screening was progressively introduced in Victoria and the number of cases, in both categories registered annually, doubled. RESULTS: The method of detection, the pathology and treatment of these lesions are described. It is of interest that 46.5% of the in situ cancers and 68.8% of the invasive cancers were detected either by the patient or her doctor on clinical examination. Total mastectomy was the method of treatment in 35.4% of in situ cancers and 42.0% of small invasive tumours. Only 38.0% of patients with small invasive cancers treated by breast-conserving surgery had irradiation of the affected breast. CONCLUSIONS: This register provides a valuable resource for the follow up of the natural history and outcome of treatment of the affected women.
The number and size of melanocytic naevi are the main predictors of cutaneous melanoma. Naevus development per unit of skin surface is greatest during childhood. We assessed the body distribution of naevi 2-4.9 mm and > or = 5 mm in 649 European children aged 6-7 years old from Brussels (Belgium), Bochum (Germany), Lyon (France) and Rome (Italy). The numbers of naevi 2-4.9 mm and naevi > or = 5 mm were strongly correlated, especially on the trunk. For naevi 2-4.9 mm, the highest relative densities were found on the face, back, shoulders and the external surface of the arms. The lowest relative densities were found on the hands, legs, feet and abdomen. The relative density of naevi > or = 5 mm was higher on the trunk than on any other body site. Similar body distributions were observed in both sexes and at each centre. The body site distribution of naevi 2-4.9 mm seemed to parallel the usual sun exposure patterns of young European children. It is suggested that the development of naevi > or = 5 mm might be a marker of the vulnerability of melanocytes to the harmful effects of solar radiation. Vulnerability would be maximal on the back, and would decrease from proximal to distal skin areas, with melanocytes of the hands and feet having the lowest vulnerability. The number of naevi acquired on a specific area of skin would result from the combined effects of local vulnerability to solar radiation and local sun exposure history. The origin of acquired body site differences in the susceptibility of melanocytes to ultraviolet radiation is unknown, although it seems to parallel the body site density of sensory innervation.
This article reports on the evaluation of the first year of a project, which utilized learning sets to support librarians undergoing the accreditation process, in the health libraries in the West Midlands region of the NHS. The West Midlands Health region is divided up into education consortia patches. Each group of patch librarians was allocated a local accreditation facilitator. The groups met regularly to discuss problems and progress relating to their library's accreditation. The results of the evaluation suggest that this is a valuable approach to use. The recommendations state that regular, frequent meetings are needed. Extra training and guidance would help the facilitators to be more effective in their role.
OBJECTIVE: To assess the validity of the Anti Cancer Council of Victoria food frequency questionnaire (ACCVFFQ) relative to seven-day weighed food records (WFRs) in 63 women of child-bearing age. METHOD: 63 women completed WFRs to assess iron intake as part of a study on iron deficiency. These women also completed the ACCVFFQ. Nutrient intakes were computed independently for the WFRs and FFQs. Intakes were compared as group means, by correlation and by quintile classification, adjusting for day-to-day variation in intakes, and for energy intake. Individual differences in results were also examined. RESULTS: The strongest associations between WFR and FFQ results were energy-adjusted, log-transformed and adjusted for day-to-day variability in intake. Correlation coefficients ranged from 0.28 for vitamin A to 0.78 for carbohydrate. Mean intakes from the WFRs and FFQs were within +/- 20% for 21 of 27 nutrients. Poor agreement between FFQs and WFRs for retinol intake was due to the inclusion of liver in two WFRs, an item which is not included in the FFQ. CONCLUSION: The ACCVFFQ performs as well as other FFQs for which validation data are available. The relatively poor measurement of retinol is consistent with other data, and with the limited number of foods in which this nutrient is abundant. IMPLICATIONS: The availability of an optically scannable valid instrument for assessing dietary intake will facilitate epidemiological studies of diet and disease, an area of current research priority.
Explore the source record for details and available documents.
BACKGROUND: We investigated the incidence of invasive cancer of the breast, ovary, and uterus in a cohort of patients who had undergone in-vitro-fertilisation (IVF) treatment and examined whether cause of infertility or exposure to fertility drugs to induce superovulation was associated with an increased cancer risk. METHOD: Ten Australian IVF clinics provided data for women who had been referred for IVF before Jan 1, 1994. The frequencies of invasive breast, ovarian, and uterine cancer were assessed by record linkage to population-based cancer registries and the national death index. The observed number of cancers was compared with the expected number calculated by application of age-standardised general-population cancer rates to the cohort. Standardised incidence ratios (SIRs) were derived from the ratio of observed to expected cases. FINDINGS: The cohort consisted of 29,700 women: 20,656 were exposed to fertility drugs and 9044 were not. 143 breast cancers, 13 ovarian cancers, and 12 cancers of the uterus occurred among these women. For breast and ovarian cancer the incidence was no greater than expected (SIR 0.91 [95% CI 0.74-1.13] for breast cancer and 0.88 [0.42-1.84] for ovarian cancer in the exposed group and 0.95 [0.73-1.23] for breast cancer and 1.16 [0.52-2.59] for ovarian cancer in the unexposed group). The incidence of uterine cancer was no higher than expected in the exposed group (1.09 [0.45-2.61]) but was significantly higher in the unexposed group (2.47 [1.18-5.18]). Women with unexplained infertility had significantly more cancers of the ovary and uterus than expected (2.64 [1.10-6.35] and 4.59 [1.91-11.0], whole cohort). Analysis of cancer incidence within 12 months of exposure to fertility drugs with IVF showed that incidence was significantly higher than expected for breast and uterine cancer (1.96 [1.22-3.15] and 4.96 [1.24-19.8]). INTERPRETATION: Women who have been exposed to fertility drugs with IVF seem to have a transient increase in the risk of having breast or uterine cancer diagnosed in the first year after treatment, though the incidence overall is no greater than expected. Unexplained infertility was associated with an increased risk of a diagnosis of ovarian or uterine cancer.
OBJECTIVES: Because the factors that influence risk of acral melanomas on the soles and palms in White populations are unknown, we investigated these in a multi-center case-control study. METHODS: Cases of melanoma of the feet and hands diagnosed from 1987-93 in persons aged over 18 years were ascertained in eastern Australia and western Scotland. There were 275 cases of melanoma on the soles and palms matched to 496 controls (selected from the electoral roll) in Australia, and 36 cases matched to 72 controls (nominated by general practitioners) in Scotland. RESULTS: Acral melanoma was strongly associated with high total body nevus counts (adjusted relative risk [RR] = 6.3, 95% confidence interval [CI] = 2.5-15.6), and with nevi on the soles (RR = 7.5, CI = 3.0-18.6). There were also significant positive associations with a penetrative injury of the feet or hands (RR = 5.0, CI = 3.0-8.6) and with heavy exposure to agricultural chemicals (RR = 3.6, CI = 1.5-8.3). Sun-sensitive complexions, cumulative sun exposure and a past history of nonmelanoma skin cancer were also associated with increased risk of acral melanoma. Current cigarette smoking was inversely related to acral melanoma (RR = 0.6, CI = 0.4-0.9). CONCLUSIONS: Melanomas of the soles and palms resemble other cutaneous melanomas in their association with sun exposure, but are distinguished from them by their strong positive associations with nevi on the soles, previous penetrative injury, and exposure to agricultural chemicals, and by their inverse association with smoking.
Explore the source record for details and available documents.
Non-melanocytic skin cancer (NMSC) is the most common cancer in Australia, but data on its incidence are not routinely collected by cancer registries. National surveys were conducted in 1985, 1990 and 1995 to estimate NMSC incidence. Trends in incidence between 1985 and 1995 have been examined to determine the impact of primary prevention campaigns aimed at controlling skin cancer in Australia. National random household surveys of Australians aged over 13 years were used to estimate NMSC incidence in 1985, 1990 and 1995. Age- and sex-specific rates by survey year were modelled using Poisson regression. Basal cell carcinoma (BCC) rates in 1995 were 788 per 100,000, an increase of 19% since 1985. Squamous cell carcinoma (SCC) rates rose by 93% over the same period, from 166 to 321 per 100,000. The ratio of BCC:SCC changed from 4:1 in 1985 to 2.5:1 in 1995. BCC rates in latitudes <29 degrees S remained at about 3 times those in latitudes >37 degrees S over the decade. The ratio of SCC incidence between these latitudes changed from around 7:1 to 3:1 over the same period. Although NMSC incidence rates continue to rise, there have been reductions in BCC observed in younger age groups. Incidence rates of NMSC continue to rise in Australia, but there is evidence of a reduction in BCC incidence in younger cohorts. This is evidence that public health campaigns to reduce sun exposure may be having a beneficial effect on skin cancer rates.
Although much has been written, little is known about the causes of prostate cancer. Variations between populations in the incidence of invasive cancers, together with changes in the incidence of invasive cancers in migrants, have pointed to environmental (lifestyle) factors that might be amenable to intervention. Conversely, there is a lack of international variation in the prevalence of microscopic tumours, so the essential question is: what causes only some of the common microscopic tumours to become aggressive? Dietary factors hold the most promise in this regard and have been the subject of recent reviews. The strongest and most consistent effects are positive associations with animal products such as red meats, eggs and dairy foods, and possibly by implication, fat. Evidence of a protective effect of fruit and vegetables is weak and inconsistent, as is the relationship with vitamin A and carotenoids, such as beta-carotene. There are some interesting leads. Lycopene, the carotenoid found in tomatoes, has been reported to be protective; alpha-tocopherol supplementation has shown a protective effect in one intervention study; and vitamin D has been shown to be protective in a prospective study. Interest is also growing in phytoestrogens and the extent to which dietary manipulation with these and other phytochemicals might influence prostate cancer by modifying male sex hormone levels or actions. There is limited evidence of associations with obesity. It is not known whether these are related to a particular dietary pattern or to possible physiological effects on the male's hormonal milieu. Associations with lean body mass are likely to be related to the action of androgens during growth and development. Dietary and nutritional effects on prostate cancer do not appear to be strong, but they may be subtle and attenuated by measurement error. To explore these aspects further will require large prospective studies that include improved (repeated) dietary measurements and also blood sampling, so that genetic polymorphisms can be adequately investigated. Such studies are underway.
The study aimed to estimate the prevalence of risk factors for liver disease, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, in a population-based series of hepatocellular carcinoma, and to assess the feasibility of retrospective surveys in determining risk factors for hepatocellular carcinoma. A survey of all cases of hepatocellular carcinoma diagnosed in 1991 and 1992 documented the high contribution of alcoholic cirrhosis, particularly in Australian-born men. Low levels of testing for HBV and HCV made their contribution to hepatocellular carcinoma uncertain. No cases of hepatocellular carcinoma due to HBV or HCV were reported in Australian-born subjects. Higher rates of HBV carriage in those tested were found in Asian and Mediterranean immigrants. Testing for HCV was known to have occurred for less than a quarter of subjects, and assessment for multiple aetiological risk factors was rare. The burgeoning epidemic of HCV will require improved surveillance for the sequelae of long-term infection. Satisfactory surveillance will require cooperation from clinicians in regard to the completeness of medical records and adequate resources for cancer registries to supplement their passive reporting system with exposure data.
In view of the changing trends in the incidence of melanoma at different body sites and in particular on the limbs, the detailed distributions of over 10,000 invasive melanomas diagnosed on the upper and lower limbs in residents of mainland eastern Australia between 1987 and 1993 were examined. Cancer notifications and histopathology reports from the cancer registries of Queensland, New South Wales and Victoria were searched manually, and subsites when specified were recorded as shoulder, upper arm, forearm, elbow, wrist or hand, and thigh, leg, knee, ankle or foot. On the upper limbs relative tumour densities were highest on the shoulder, approximately equal on the upper arm and forearm and least on the hand in both men and women; on the lower limbs melanomas occurred more than twice as often on the leg than on the thigh or the foot, taking account of surface area. There was a clear inverse gradient of incidence of melanoma with latitude in the three eastern Australian states studied, but little difference between the states or between sexes in distribution of histological type: the majority specified being specified as superficial spreading melanomas. In contrast to predictions based on apparent frequency of sun exposure at subsites on the upper limbs, the relative concentration of melanomas on the shoulder suggests that wearing sleeveless garments outdoors in the sun should be avoided whenever possible. Also, the similar densities of leg and forearm melanomas seems inconsistent with the relative degree of exposure of each and further suggests that women's adoption of ankle-length skirts or trousers, in preference to knee-length skirts would be a worthwhile modern control measure.
BACKGROUND AND OBJECTIVE: In retrospective studies of non-melanoma skin cancers, the recurrence rates were relatively high. This study had as its aim to determine the recurrence rate of nonmelanoma skin cancer (NMSC) and prospectively, risk factors for recurrence in southern Australia. STUDY DESIGN: This is a prospective study of outpatients with histologically confirmed NMSC. All patients seen by a dermatologist between November 1988 and November 1989 were entered into the study and followed for at least 3 years. Any recurrent NMSCS were removed and recorded. RESULTS: Four hundred and eighty-one patients were entered and 420 followed for at least 3 years. A recurrent NMSC developed in 8% (adjusted for losses). A multivariate analysis determined that the main risk factor for recurrence within the first 3 years of follow-up was the number of NMSC a patient had when entering into the study. Those with 3 to nine NMSC were five times more likely to develop a recurrence than those with less than three NMSC. Those with 10 or more NMSC were 25 times more likely to develop a recurrence. Age, sex, and types of skin cancers removed were not risk factors within the first 3 years of follow-up. CONCLUSION: Patients who have had multiple skin cancers require careful follow-up because of the risk of developing recurrences.
The incidence of cancer between 1970 and 1989 in children aged less than 15 years and resident in the state of Victoria, Australia, was ascertained using records held by the Victorian Cancer Registry. Altogether, 1,189 children in the 1970s and 1,261 children in the 1980s were registered with new diagnoses of cancer and these were followed up until 30 June 1993. Between 1970-1979 and 1980-1989 the incidence of childhood cancer rose by 14%, but this was not statistically significant. Part of this apparent increase may have been due to improved registration of cases in the 1980s, particularly of certain tumour types, and of tumours in older children who may have been treated outside the major paediatric treatment centres. Between the 2 decades, 5-year survival increased from 49% to 67%, with improvements in almost all tumour types. Only in Ewing's sarcoma did survival proportions decrease, and this may be related to histological misclassification and to an increased proportion of Ewing's arising in the pelvis during the 1980s. There is evidence already that with new treatment regimens introduced during the 1980s survival in the 1990s will show increased gains.