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Biomedical subjects

B K Armstrong

Publications and source records attributed to B K Armstrong.

At least 37 records · Page 2Linked to original sources

UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma.

BACKGROUND: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure. METHODS: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site. CONCLUSIONS: Our results indicate that tandem CC --> TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure.

Adult↗

Breast cancer mortality trends in Australia: 1921 to 1994.

OBJECTIVE: To analyse breast cancer mortality trends in Australia and to see if mammographic screening has yet led to a reduction in mortality. DESIGN: Retrospective analysis of trends in mortality rates from breast cancer in Australian women between 1921 and 1994, and in potentially explanatory variables such as fertility, body size, age at menarche, and screening. RESULTS: Changes in breast cancer mortality in Australian women could not be explained by chance variation alone. Mortality rose steadily (average annual increase, 1.0%) to 1940-1944, fell to the 1960s and early 1970s, and rose (average annual increase, 0.3%) to the late 1980s. Between 1985-1989 and 1990-1994, breast cancer mortality fell by 3.2% in women 50-69 years of age (the target age group for mammographic screening) and by 4.2% in women 25-49 years of age. There was almost on change (-0.2%) in breast cancer mortality in older women in this period. The proportion of women screened in all age groups increased substantially between 1988 and 1994; nearly 65% of women in the target age group had had at least one mammogram by 1994. Decreases in fertility were followed by increases in mortality, and vice versa. CONCLUSIONS: Trends in breast cancer mortality have probably been influenced by changing fertility, nutrition and body-size increases among Australian women. Improvements in stage at diagnosis and treatment have probably moderated the upwards pressure on mortality caused by an increasing incidence. Recent falls in mortality could be expected to continue as more women participate in the mammographic screening program. This trend should be more clearly evident in the second half of the 1990s.

Adult↗

General practitioner screening for melanoma: sensitivity, specificity, and effect of training.

OBJECTIVE: To measure the performance of trained and untrained general practitioners (GPs) in screening men and women aged 50 or more for melanomas. METHODS: GPs trained in melanoma diagnosis, untrained GPs, and skin cancer specialists examined groups of volunteers, each of which included a small number of subjects with prediagnosed suspicious pigmented lesions (SPLs) that were subsequently excised for histopathological examination. RESULTS: Trained and untrained GPs achieved mean sensitivities of 0.73 and 0.71, and mean predictive values of 0.40 and 0.37, respectively, for the detection of prediagnosed SPLs. When the SPLs had been excised and examined histopathologically, reanalysis showed mean sensitivities of 0.98 and 0.95, mean specificities of 0.52 and 0.49, and mean positive predictive values of 0.24 and 0.22 for the detection of subjects with melanomas by trained and untrained GPs respectively. Trained GPs were significantly better than untrained GPs at diagnosing as melanomas SPLs that subsequently proved to be melanomas (p = 0.04). CONCLUSIONS: GPs in this study achieved high sensitivities in screening older Australian men and women for melanomas, but at the cost of low specificities and positive predictive values. Training in melanoma diagnosis had no significant effect on sensitivity, specificity, and positive predictive value for screening. Data from the study were tested in a model of population screening for melanomas, and costs per life year saved for men aged 50-70 ranged from $A11,852 to $A40,259 depending upon the screening interval and whether the GPs excised the SPLs diagnosed, or referred all patients to skin cancer specialists; this would be as cost effective as cervical cancer screening.

Female↗

Reproducibility of reported measurements of sun exposure in a case-control study.

We examined the reproducibility of the measurement of sun exposure in a cohort study of nonmelanocytic skin cancer in Geraldton, Western Australia. Two analyses were undertaken: a comparison of cutaneous sun damage with sun exposure reported at interview, and an analysis of test-retest reproducibility of reported exposure. Skin cancers and cutaneous indicators of sun damage (cutaneous microtopography and solar elastosis of the neck) were recorded at a survey in 1987. A case-control study was conducted in 1988 in which subjects were interviewed about their lifetime sun exposure. All subjects had European ancestry. A subset of these subjects was reinterviewed using the same interview schedule in 1993. The comparison of reported exposure with skin damage was restricted to 201 cases of basal cell carcinoma and 700 controls, all of whom were born in Australia and had no southern European ancestors. The analysis of test-retest reproducibility included 62 cases with basal cell carcinoma and 162 controls. After adjustment for the skin's sensitivity to sunlight, cutaneous microtopography explained 7% and solar elastosis of the back of the neck explained 13% of the variance in the reported time spent outdoors. The intraclass correlation between time spent outdoors reported in the two interviews was 0.77 [95% confidence interval (CI), 0.71-0.83], whereas for exposure to a specific anatomical site, it was 0.65 (95% CI, 0.55-0.73). The reported site-specific exposure was lower on the second occasion in controls but higher in cases. The hours of exposure on vacations and the proportion of exposure that occurred on nonworking days had poor reproducibility. Furthermore, cases reported a more intermittent pattern of weekly exposure on the first occasion than on the second, whereas the controls showed little difference in their pattern on the two occasions. The weighted kappa statistic for lifetime painful sunburns was 0.53 (95% CI, 0.41-0.66), and for lifetime number of blistering sunburns, it was 0.54 (95% CI, 0.44-0.65). Thus, the reported sun exposure showed only moderate agreement with biological markers of sun damage. Total sun exposure and, to a lesser extent, site-specific exposure showed good agreement on the two occasions. However, indicators of intermittent sun exposure had poor agreement, and sunburn had only fair agreement.

Adult↗

Incidence of non-melanocytic skin cancer in Geraldton, Western Australia.

To measure the rate at which non-melanocytic skin cancers develop, we conducted a population-based, longitudinal study in Geraldton, Western Australia. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age and registered on the electoral roll in 1987. In 1987 and again in 1992, dermatologists examined participants for skin cancers. They examined all skin areas, apart from those covered by underwear or hair. Subjects were asked about skin cancers that they had had treated between the 2 surveys. When all skin cancers were counted, the incidence rates of basal cell carcinoma were 3,379 per 100,000 person-years in women and 7,067 per 100,000 in men; those of squamous cell carcinoma were 501 per 100,000 in women and 775 per 100,000 in men. Sixteen percent of men and 14% of women developed at least one basal cell carcinoma; 2.8% of men and 2.2% of women had at least one squamous cell carcinoma. Most incident skin cancers were diagnosed at the second examination. More than half of the subjects who had a skin cancer at the first examination developed another. Squamous cell carcinomas occurred almost exclusively on parts of the body that are usually exposed. Basal cell carcinomas were common on the head, neck and trunk but not on the forearms and backs of hands. A quarter of people with a skin cancer on an exposed site also had one on the trunk. Our results show that skin cancer is extremely common in this population and frequently undiagnosed. Multiple skin cancers occur commonly, and skin cancers on exposed sites often are associated with skin cancers on less exposed sites.

Adult↗

Trends in colorectal cancer incidence and mortality in New South Wales, 1973-1992.

OBJECTIVE: To assess changes in incidence and mortality rates of colorectal cancer in different age groups in New South Wales (NSW) between 1973 and 1992. DESIGN: Descriptive analysis of data on incidence and mortality from the population-based NSW Central Cancer Registry and on colorectal cancer diagnostic tests from the Health Insurance Commission. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates for colon and rectal cancer (defined by codes 153 and 154 in the International classification of diseases, 9th revision) by sex and age group (15-44, 45-59, 60-74 or > or = 75 years) and incidence by cancer spread at diagnosis; age-standardised rates for faecal occult blood tests, sigmoidoscopy and colonoscopy. RESULTS: From 1973 to 1992, colorectal cancer incidence increased significantly in NSW by an average of 2.0% per year in males (95% confidence interval [CI], 1.8 to 2.3) and 0.9% in females (95% CI, 0.7 to 1.1). Mortality rates remained nearly constant in males, but fell significantly in females by an average of -1.0% per year (95% CI, -1.3 to -0.7). In the youngest age group (15-44 years) both incidence and mortality rates fell significantly, while rates were stable or rose in older age groups, except for a significant fall in mortality in women aged > or = 75 years. Use of colonoscopy (an early detection method) increased, but a corresponding shift to detection of earlier-stage cancers was not seen. CONCLUSIONS: A reduction in risk factors and better treatment leading to longer survival may have contributed to the falls in incidence in younger people and in mortality in females.

Adolescent↗

Sunlight and cancer.

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Australia↗

Sun exposure and skin cancer.

By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.

Australia↗

Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994.

OBJECTIVE: To describe recent trends in mortality from melanoma in Australia. DESIGN: An analysis of trends in age standardised and age and sex specific mortalities by year of death and median year of birth (cohort). SETTING: Australia. SUBJECTS: All deaths from melanoma registered in Australia between 1931 and 1994. RESULTS: Melanoma mortality rose steadily from 1931 to 1985. From 1959 the annual rate of increase was 6.3% in men and 2.9% in women, resulting in mortalities of 4.82 and 2.51 per 100,000 person years in 1985 and 1989, respectively. Mortalities for both sexes seem to have plateaued from June 1985 onwards. In 1990-4 the rate rose by 3.7% in men to 5.00 per 100,000 and in women it fell by 5.2% to 2.38 per 100,000. The non-significant increase after 1985 in mortality in men was restricted to those aged over 70 years of age, whereas the fall in rates in women was mostly in those aged under 55 years. This pattern was generally reflected in the state trends, though with some variation: rates for women in Queensland had peaked in the late 1970s; while rates for men in New South Wales continued to rise in 1990-4, placing them above those for Queensland. Examination of mortalities specific for age, period, and cohort for Australia as a whole showed several salient features. Rates in men rose steeply in cohorts born before about 1930; were stable in cohorts born between 1930 and 1950; and fell in more recent cohorts. Rates in women showed similar changes but about five years earlier. CONCLUSION: Melanoma mortality in Australia peaked in about 1985 and has now plateaued. On the basis of trends in cohorts it can be expected to fall in coming years.

Adolescent↗

Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.

BACKGROUND: We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.

Adolescent↗

Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The International Melanoma Analysis Group (IMAGE).

Using individual subject data from 10 case-control studies, comprising over 3000 cases and almost 4000 controls, we have estimated the relative risk of melanoma associated with aspects of complexion, namely, hair, eye and skin colour and freckling in adulthood, and have examined the relationships between these factors and naevus count in terms of melanoma risk. Compared with individuals with black or dark brown hair, the relative risks for developing melanoma in those with light brown, blonde and red hair were 1.49 (95% CI 1.31, 1.70), 1.84 (95% CI 1.54, 2.21) and 2.38 (95% CI 1.90, 2.97), respectively. Individuals with blue eyes had a risk 1.55 (95% CI 1.35, 1.78) times that for those with brown eyes, or 1.15 (95% CI 0.94, 1.40) after adjusting for hair colour and freckling in adulthood. The relative risks associated with hair and eye colour were independent of those for naevus count and skin colour. Light skin colour and high freckle density were also highly significant risk factors, independent of each other and of naevus count and hair and eye colour. The risks associated with these factors, while individually modest, are largely independent, and thus pigmentation characteristics and freckling tendency should be useful in identifying high risk groups to be targeted for prevention.

Case-Control Studies↗