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Biomedical subjects

D F Austin

Publications and source records attributed to D F Austin.

At least 55 records · Page 3Linked to original sources

Marriage and divorce after childhood and adolescent cancer.

As part of a study of long-term survivors of childhood and adolescent cancer, we interviewed 2170 survivors and 3138 sibling control subjects about their marital histories. In a proportional hazards analysis, both male and female survivors were less likely to be ever married than control subjects (rate ratio [RR] for males, 0.87; 99% confidence interval, 0.76 to 0.99; RR for females, 0.86; 99% confidence interval, 0.76 to 0.97). Survivors of brain and central nervous system tumors accounted for most of the marriage deficit, which was greater in men than in women (RRs, 0.48 and 0.73, respectively). Survivors married at the same average age as control subjects, except for survivors of central nervous system tumors, who married slightly later. The average length of first marriages was shorter in survivors than in control subjects. Men who had survived central nervous system tumors diagnosed before 10 years of age and male survivors of retinoblastoma had higher divorce rates than male control subjects (RRs, 2.9 and 1.9, respectively). In this cohort (which received less intense therapy than given in current practice), altered marriage practices are substantial only among survivors of central nervous system tumors.

Adolescent↗

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Adult↗

Adenoidectomy for secretory otitis media.

Thirty years of treating secretory otitis media by what is presently considered an alternate approach is discussed. Early experience with using a polyethylene tube in one ear only led to a formal study of the efficacy of polyethylene tube use when combined with adenoidectomy or adenotonsillectomy. This study included 31 children with chronic bilateral secretory otitis media treated by tonsillectomy and adenoidectomy. At the time of surgery, one ear was intubated and the other served as a control with no treatment. Using audiometric criteria, it was found that there was no significant difference between the intubated and control ears after a 6- to 8-week follow-up. Also documented is a series of 425 children suffering from chronic secretory otitis media, all of whom were resistant to prior ear, nose, and throat or pediatric treatment. Fifty-three children had tonsillectomies and adenoidectomies without tube insertion and were followed up for at least 1 year. Audiometry was used to measure the result of therapy that was successful in more than 90% of the patients.

Adenoidectomy↗

Staging in cholesteatoma surgery.

Single stage surgery was used for 174 operations for cholesteatoma. The results were analysed using months at risk (actuarial) statistics. The methods of data collection and of creating a life-table for cholesteatoma follow-up are described. Ninety-one canal-down procedures are compared with 82 canal-up procedures as to the recidivism rate as well as hearing results. The actuarial tables showed a 50 per cent cumulative success rate for canal-up procedures versus a 90 per cent rate for canal-down operations. The successful canal-up procedures, however, demonstrated slightly better hearing results. These success rates seemed to be comparable to those using planned staged surgery. It was concluded that if single stage canal-up procedures were used with larger mastoids and canal-down procedures with smaller mastoids, 80 per cent of patients could be controlled without either residual or recurrent disease appearing. For the others, it was felt safe to wait for the disease to reappear rather than to do planned two-stage procedures for all patients. It was further urged that actuarial statistics be employed when reporting the results of surgery for cholesteatoma.

Actuarial Analysis↗

Single-stage surgery for cholesteatoma: an actuarial analysis.

Single-stage surgery was used for 215 operations for cholesteatoma. The results were analyzed using months at risk (actuarial) statistics. The methods of data collection and of creating a life-table for cholesteatoma follow-up are described. Ninety-one canal-down procedures are compared with 124 canal-up procedures as to the recidivism rate as well as hearing results. The actuarial tables showed a 45% cumulative success rate for canal-up procedures versus a 90% rate for canal-down operations. The successful canal-up procedures demonstrated slightly better hearing results, however. These success rates seemed to be comparable to those using planned staged surgery. It was concluded that, if single-stage canal-up procedures were used with larger mastoids and canal-down procedures with smaller mastoids, 80% of patients could be controlled without either residual or recurrent disease appearing. For the others, it was felt safe to wait for the disease to reappear rather than to do planned two-stage procedures for all patients. It was further urged that actuarial statistics be employed when reporting the results of surgery for cholesteatoma.

Actuarial Analysis↗

Assessment of potential for cancer control by Golden State Medical Association physicians.

To gather data on which to base the design of an intervention program to decrease cancer mortality in the black population of California, physician members of the Golden State Medical Association were surveyed to determine their current practices relating to early cancer detection and cancer prevention. Respondents' estimates of the proportions of their patients in various categories indicated that at least 60% to 70% of their patients were potential subjects for intensive early cancer detection and cancer prevention efforts. Thirty-four percent of respondents reported that they were performing early cancer detection examinations on all their patients. On the average, respondents estimated that about 70% of their patients (more than 80% of patients of primary care physicians) were receiving either routine check-ups or specific early cancer detection examinations. Patient education about various aspects of cancer and cancer prevention emerged as the most readily attainable means to reduce cancer mortality in blacks. It was most frequently mentioned both as something that physicians could do to help achieve this goal and as an outside resource physicians would find useful in their practices. Its lack was cited as the greatest barrier to early cancer detection and cancer prevention in the black population.

Adult↗

Dietary factors in oral and pharyngeal cancer.

A population-based case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on a number of risk factors, including diet. Interviews were obtained from 871 oral cancer patients and 979 controls among whites, frequency matched for age and sex. Consumption frequency of 61 food items was assessed in the questionnaire; attention was given to foods that are sources of vitamins A and C and carotene. The major finding was an inverse relationship between fruit intake and risk of oral and pharyngeal cancer; individuals in the highest quartile of intake had about half the risk of those in the lowest quartile. Vitamin C, carotene, or fiber in fruit did not appear to account completely for this relationship, since these nutrients in vegetables did not provide similar protection. This finding suggests the influence of other constituents in fruits, although it is possible that cooking vegetables may have a nutrient-diminishing effect. Dietary intake of other nutrients, such as the B vitamins, vitamin E, folate, and iron, showed no consistent relationship to risk of oral and pharyngeal cancer. Coffee or other hot beverage consumption did not increase risk; intake of nitrite-containing meats or cooking practices, such as smoking, pickling, or charcoal grilling, also did not increase risk. All analyses were adjusted for the effects of tobacco and alcohol, strong risk factors for oral and pharyngeal cancer. Dietary findings among the few subjects who did not use tobacco or alcohol were similar to those for all subjects.

Adult↗

Smoking and drinking in relation to oral and pharyngeal cancer.

A case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on the tobacco and alcohol use of 1114 patients and 1268 population-based controls. Because of the large study size, it could be shown that the risks of these cancers among nondrinkers increased with amount smoked, and conversely that the risks among nonsmokers increased with the level of alcohol intake. Among consumers of both products, risks of oropharyngeal cancer tended to combine more in a multiplicative than additive fashion and were increased more than 35-fold among those who consumed two or more packs of cigarettes and more than four alcoholic drinks/day. Cigarette, cigar, and pipe smoking were separately implicated, although it was shown for the first time that risk was not as high among male lifelong filter cigarette smokers. Cessation of smoking was associated with a sharply reduced risk of this cancer, with no excess detected among those having quit for 10 or more years, suggesting that smoking affects primarily a late stage in the process of oropharyngeal carcinogenesis. The risks varied by type of alcoholic beverage, being higher among those consuming hard liquor or beer than wine. The relative risk patterns were generally similar among whites and blacks, and among males and females, and showed little difference when oral and pharyngeal cancers were analyzed separately. From calculations of attributable risk, we estimate that tobacco smoking and alcohol drinking combine to account for approximately three-fourths of all oral and pharyngeal cancers in the United States.

Black or African American↗

Case-control study of gestational choriocarcinoma.

A multicentered case-control study of 75 women who had had gestational choriocarcinoma was conducted to investigate the role of reproductive and fertility factors as well as other potential risk factors in the development of this disease. Control women, identified through random digit dialing, were individually matched to cases by year of pregnancy, age at pregnancy, and geographical proximity of residence. Choriocarcinoma risk was decreased significantly as body mass index increased (P for trend = 0.03). Cases reported low-calorie dieting significantly less frequently than controls [odds ratio estimate (OR) = 0.50, P = 0.05] and were significantly less likely to participate in regular exercise (OR = 0.38, P = 0.004). Compared to women with a heavy menstrual flow, those with light menstruation had significantly elevated risk (OR = 6.69, P = 0.01). Menarche after age 12 was also associated with elevated risk of this disease (OR = 2.89, P = 0.003). There were significantly more pairs of dizygotic twins born to cases and their first degree relatives than to controls (12 case families with 13 sets of twins versus 3 sets in control families, OR = 6.36, P = 0.009). Cases were more likely to have married more than once (OR = 13.0, P less than 0.001), and infrequent intercourse was a significant risk factor (OR for weekly or less often was 3.00, P = 0.04). Risk estimates for postmolar choriocarcinoma were not significantly different from those for all other cases. These observations and some descriptive features of the disease suggest that hormonal factors, specifically below normal estrogen levels, may be associated with a disruption of normal ovulation and thus predispose to choriocarcinoma.

Adult↗

Educational achievement of long-term survivors of childhood and adolescent cancer.

In a retrospective cohort study, the level of education attained by 2,283 long-term survivors of childhood and adolescent cancer was investigated and compared with that of 3,270 sibling controls. Survivors of central nervous system tumors were significantly less likely than controls to complete eight grades of school or, if they completed high school, to enter college. No significant differences in educational achievement were found for survivors of non-central nervous system cancers. The educational deficit of survivors of brain tumors was especially striking for tumors of the ventricles or cerebral hemispheres, and the deficit was more severe for those treated with radiation therapy than by surgery alone. Early age at diagnosis of a central nervous system tumor was associated with a larger educational deficit than late age at diagnosis. These findings are reassuring for the majority of long-term survivors of childhood and adolescent cancers given therapies used prior to 1975.

Adult↗

Use of a population-based tumor registry to estimate cancer incidence among a cohort of chemical workers.

There have been many studies conducted of mortality in occupational cohorts, but few of cancer incidence. Two major facilities of the Western Division of Dow Chemical USA are located fortuitously within an area covered by the population-based California Tumor Registry, which allowed linkage of records to identify incident cancers among 1,403 male workers. Using adjusted county rates for comparison, 49 new cancers were observed in the cohort from 1969 through 1983, whereas 63.0 were expected (standardized incidence ratio = 78, 95% confidence limits = 53 to 103). Nonsignificant excesses were noted for several cancer groups among some categories of workers; however, there was no predominant tumor type within the groups. The successful completion of this collaborative project suggests that using population-based tumor registries for surveillance of occupational cohorts is feasible.

Adult↗

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Female↗

Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer.

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease.

Adolescent↗

Cancer in offspring of long-term survivors of childhood and adolescent cancer.

A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person-years of follow-up in the second decade of life, when most cases of cancer developed, was small.

Adolescent↗

Bladder cancer, drinking water source, and tap water consumption: a case-control study.

Data from a population-based case-control interview study of incident bladder cancer in 10 areas of the United States were used to estimate relative risks among white men (2,116 cases, 3,892 controls) and women (689 cases, 1,366 controls) according to beverage intake level and type of water source. Individual year-by-year profiles of water source and treatment were developed by linking lifetime residential information with historical water utility data from an ancillary survey. Risk of bladder cancer increased with intake level of beverages made with tap water. The odds ratio (OR) for the highest vs. lowest quintile of tap water consumption was 1.43 [95% confidence interval (CI) = 1.23, 1.67; chi 2 for trend = 26.3, P less than .001]. The risk gradient with intake was restricted to persons with at least a 40-year exposure to chlorinated surface water and was not found among long-term users of nonchlorinated ground water. The ORs for the highest vs. lowest quintiles of tap water intake were 1.7 and 2.0, respectively, among subjects with 40-59 and greater than or equal to 60 years' exposure. Duration of exposure to chlorinated surface water was associated with bladder cancer risk among women and nonsmokers of both sexes. Among non-smoking respondents with tap water consumption above the population median, the OR increased with exposure duration to a level of 3.1 (CI = 1.3, 7.3; chi 2 for trend = 6.3, P = .01) for greater than or equal to 60 years of residence at places served by chlorinated surface water (vs. non-chlorinated ground water users). These results extend findings of earlier epidemiologic studies and are consistent with environmental chemistry and toxicologic data demonstrating the presence of genotoxic by-products of chlorine disinfection in treated surface waters.

Chlorine↗

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Adult↗