Increase in cancer of the corpus uteri in the San Francisco-Oakland standard metropolitan statistical area, 1960--75.

A significant rise in the incidence of carcinoma of the corpus uteri in women of the San Francisco-Oakland standard metropolitan statistical area (SMSA) was reported by the Resource for Cancer Epidemiology. The incidence among white females increased by over 50% in the 6 years between 1969 and 1975. The increase was limited to the groups over 50 years old and to invasive cancers of the endometrial lining. The increase occurred in all five of the SMSA counties and, in white women in Aalmeda County, the average annual incidence for the 50- to 74-year age group tripled in 15 years. The rise was greatest in the areas of most affluence. Possible spurious causes of increase, such as changing diagnostic criteria, better case finding, or better reporting were examined and ruled out. The data suggested that the increase was due to the recent introduction of a potent endometrial carcinogen to the population group affected.

Breast cancer in men: aspects of familial aggregation.

Familial aggregation of breast cancer in males was investigated in a population-based case-control study. Cases were ascertained from 10 Surveillance, Epidemiology, and End Results Program registries in the United States between 1983 and 1986. Controls were identified by random-digit dialing and from lists of Medicare recipients. The relative odds of developing breast cancer were similar in men with affected paternal and maternal relatives and in men with affected mothers and sisters. The risk increased with the number of affected relatives. The relative odds of developing breast cancer were greater in men with first-degree relatives who developed their mammary neoplasm before the age of 45 than in men with older first-degree affected relatives; the enhancement of risk in men with an affected sister was greater in those under age 60 than in older men. These results are similar to those observed by others in studies of breast cancer in women.

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.

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.

Racial differences in risk of oral and pharyngeal cancer: alcohol, tobacco, and other determinants.

BACKGROUND: In the United States, Blacks have increasingly higher rates of oral and pharyngeal cancer (oral cancer) than Whites, but determinants of the racial disparity have not been clear. PURPOSE: The purpose of this study was to explore reasons for the higher incidence of oral cancer among Blacks than Whites. METHODS: We used data from a large, population-based case-control study of oral cancer risk factors conducted in four areas of the United States. On the basis of interviews that ascertained characteristics of 1065 oral cancer patients (871 Whites and 194 Blacks) and 1182 controls (979 Whites and 203 Blacks), we examined racial differences in exposure prevalences and relative risks for a number of known etiologic factors, including tobacco and alcohol consumption, diet, and socioeconomic and other variables. To evaluate the extent to which the major risk factors explained the excess risk of oral cancer among Blacks, population-attributable risks were calculated. RESULTS: Differences with respect to alcohol consumption, especially among current smokers, emerged as the most important explanatory variables. After adjusting for smoking, heavy drinking (> or = 30 drinks/week) resulted in a 17-fold increased risk among Blacks and a ninefold increase among Whites. Among drinkers, Blacks tended to drink more than Whites. Also, a higher (P = .01) percentage of Blacks (37%) than Whites (28%) were current smokers, although there were little or no racial differences in relative risks or patterns of use for other smoking variables, including number of cigarettes smoked per day, years of smoking, and age started smoking. From population-attributable risk calculations, we estimated that differences in alcohol and tobacco use account for the bulk of the higher incidence of oral cancer among Blacks in the United States and that, in the absence of alcohol and tobacco, the rates of this cancer according to race (Black, White) and gender would be nearly equal. With regard to other potential etiologic factors, protective effects provided by higher dietary intake of fruits and vitamin C were more pronounced for Whites, while Blacks more often tended to be in sociodemographic and medical or dental health categories associated with increased risk. CONCLUSIONS: These analyses provide evidence that various environmental or lifestyle determinants of oral cancer may contribute to the higher oral cancer rates in Blacks than in Whites in the United States, but that patterns and risks associated with alcohol consumption, particularly among current smokers, are the most important contributors to the excess risk in Blacks. IMPLICATIONS: These findings suggest that the key to prevention of oral and pharyngeal cancers among both Blacks and Whites is reduced intake of alcoholic beverages and, because of strong interactive effects, the cessation of smoking.

Breast cancer: factors associated with stage at diagnosis in black and white women. Black/White Cancer Survival Study Group.

BACKGROUND: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences. PURPOSE: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care access factors to cancer staging at diagnosis in Black and White breast cancer patients. METHODS: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables. RESULTS: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P < .02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV cancer versus stage I-IIN0 cancer among Blacks compared with Whites (odds ratio reduction from 2.19 to 1.68). CONCLUSION: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients.

Determinants of black/white differences in colon cancer survival.

BACKGROUND: Blacks have lower survival rates for colon cancer than whites, possibly related to more advanced stages of disease at diagnosis and to socioeconomic differences between blacks and whites. While the black/white difference in colon cancer survival is well documented, the few studies that have investigated this difference have been limited by the modest number and type of explanatory factors that were considered. PURPOSE: We analyzed data from the National Cancer Institute Black/White Cancer Survival Study to determine 1) what characteristics might contribute to the racial difference in colon cancer survival and 2) if a survival disparity remained between black and white patients after adjustment was made for these characteristics. METHODS: This prospective study included 454 blacks and a stratified random sample of 521 whites, aged 20-79 years, with cancer of the colon diagnosed from January 1, 1985, through December 31, 1986, and who were residents of the metropolitan areas of Atlanta, New Orleans, and San Francisco/Oakland. Follow-up was truncated on December 31, 1990. Cox proportional hazards regression was used to estimate the death rate among blacks relative to that among whites after adjustment for potential explanatory factors, including sociodemographic factors, concurrent (comorbid) medical conditions, stage at diagnosis, tumor characteristics, and treatment. All P values were calculated from two-tailed tests of statistical significance. RESULTS: After adjustment for age, sex, and geographic area, the black-to-white mortality hazard ratio (HR) was 1.5 (95% confidence interval [CI] = 1.2-1.9), indicating that the risk of death among black patients was 50% higher than that among white patients. Further adjustment for stage reduced the excess cancer mortality to 20% (HR = 1.2; 95% CI = 1.0-1.5), decreasing the overall racial difference in excess mortality from 50% to 20% or to a 60% reduction in excess mortality. Although adjustment for poverty reduced the excess mortality by 20%, adjusting for both stage and poverty did not further reduce the racial difference. Among patients with stages II and III disease, blacks had lower survival rates than whites (HR = 1.8; 95% CI = 1.0-3.1 and HR - 1.5; 95% CI = 1.0-2.3, respectively). Among those patients with metastatic disease (stage IV), survival was similar for whites and blacks. CONCLUSIONS: Stage at diagnosis accounted for more than half of the excess colon cancer mortality observed among blacks. Poverty and other socioeconomic conditions, general health status, tumor characteristics, and general patterns of treatment did not further explain the remaining survival disadvantage among blacks. IMPLICATIONS: Because the racial disparity was confined to earlier stages, future studies should investigate whether blacks have more advanced disease at diagnosis and whether less aggressive treatment is provided because of understanding.

Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol.

BACKGROUND: The exceptionally high rate of second primary cancers among patients with oral and pharyngeal cancers is well recognized, yet there has been limited epidemiologic study of risk factors for second tumors. PURPOSE: To evaluate the relation of smoking and alcohol consumption to the development of second cancers among this high-risk patient group, we conducted a nested case-control study. METHODS: A total of 1090 patients enrolled in a 1984-1985 population-based, case-control study of oral cancer in four areas of the United States were followed through June 1989 for the occurrence of second primary cancers. Information on tobacco and alcohol consumption was obtained from the original interviews and was updated by follow-up interviews obtained for 80 case patients with second cancers and 189 sex-, study area-, and survival-matched cancer patients free of second cancers (control subjects). RESULTS: Tobacco smoking and alcohol drinking each contributed to risk of second cancers, with the effects of smoking more pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for alcohol) rose with duration and intensity of smoking and were strongest for tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as of the baseline survey experienced a fourfold increased risk of a second aerodigestive tract cancer relative to nonsmokers and former smokers. No reduction in risk was associated with cessation of smoking or drinking at or after the index diagnosis, although the short median interval (27 months) between tumor diagnoses limited observation of the effects due to recent cessation. Risk was significantly reduced, however, 5 years after smoking cessation. Among drinkers, second cancer risk was greatest for beer intake, with an OR for a second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers per week. CONCLUSIONS: Oral and pharyngeal cancer patients with the highest intakes of tobacco and alcohol are the ones most prone to develop second primary cancers. IMPLICATIONS: Avoidance of tobacco smoking and alcohol drinking is the most desirable way not only to prevent primary oral cancers, but also to reduce risk of second cancers of the aerodigestive system.

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.

Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer.

Interviews with 866 patients with cancer of the oral cavity and pharynx and 1249 controls of similar age and sex from the general population in four areas of the United States revealed increased risks associated with the regular use of mouthwash. Risks of oral cancer were elevated by 40% among male and 60% among female mouthwash users, after adjusting for tobacco and alcohol consumption. Risks among both sexes generally increased in proportion to duration and frequency of mouthwash use. The increased risks were confined to users of mouthwash high in alcohol content, consistent with the elevated risks associated with drinking alcoholic beverages. Except for a higher prevalence of leukoplakia among cases, little relationship was found with oral or dental conditions, although denture wearing was reported more often by patients with cancer of the gums. These findings, together with other studies, provide further incentive for clarifying the association between mouthwash use and oral cancer.

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.

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.

Use of hair dyes and risk of bladder cancer.

The relation between use of hair dyes and risk of bladder cancer was assessed using data from a case-control study of bladder cancer. Incident cases (2982) and general population controls (5782) were interviewed. The overall estimate of relative risk of bladder cancer for users of hair dyes was 1.0 (95%) confidence interval, 0.9 to 1.2) compared to nonusers. No consistent pattern of association was detected between bladder cancer risk and various indices of timing or intensity of exposure to hair dyes. Various explanations of the lack of association are discussed.

Gender differences in hospitalizations for IDDM among adolescents in California, 1991. Implications for prevention.

OBJECTIVE: Describe gender differences in hospitalizations for IDDM to investigate the need for gender-specific interventions to reduce diabetes-related morbidity. RESEARCH DESIGN AND METHODS: Analyses were based on hospital discharges with any mention of IDDM (n = 2,889) and the subset of these for IDDM as a principal diagnosis (n = 2,270) in California children, ages 0-18 years during 1991. Pregnancy-related hospitalizations were excluded. RESULTS: Females had more diabetes hospitalizations among discharges with any mention of diabetes, among discharges with diabetes as a principal diagnosis, and among discharges with diabetic ketoacidosis as a principal diagnosis. For diabetes as a principal diagnosis, females had 40% more hospitalizations, 44% more repeated hospitalizations, 23% more individuals hospitalized, and significantly higher rates of hospitalizations for ages 10-14 years (50 vs. 38 per 100,000) and for ages 15-18 years (68 vs. 29 per 100,000). Gender differences occurred primarily in adolescents, were independent of complicating conditions at the time of hospitalization, and were observed for diabetic ketoacidosis alone. CONCLUSIONS: Adolescent females had more diabetes hospitalizations than did males. The underlying cause may be biological or behavioral. Management protocols tailored for young women may be required to reduce hospitalizations for IDDM among females.

The relationship between social ties and survival among black and white breast cancer patients. National Cancer Institute Black/White Cancer Survival Study Group.

The relationship between social ties, stage of disease, and survival was analyzed in a population-based sample of 525 black and 486 white women with newly diagnosed breast cancer. There were significant differences between the two race groups in reported social ties. Using logistic regression to adjust for the effects of age, race, study area, education, and the presence of symptoms, there was little or no evidence for an association between individual network measures of social ties and stage of disease. However, a summary measure of social networks was found to be associated modestly with late stage disease, attributable in part to significantly more advanced disease among black, but not white, women reporting few friends and relatives [relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-3.0]. With adjustments for differences in stage of disease and other covariates, and with the use of Cox proportional hazards modeling to estimate hazard ratios, the absence of close ties and perceived sources of emotional support were associated significantly with an increased breast cancer death rate. White women in the lowest quartile of reported close friends and relatives had twice the breast cancer death rate of white women in the highest quartile (RR = 2.1; 95% CI = 1.1-4.4). Notably, both black and white women reporting few sources of emotional support had a higher death rate from their disease during the 5-year period of follow-up (RR = 1.8; 95% CI = 1.3-2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Lung cancer in nonsmoking women: a multicenter case-control study.

The association between exposure to environmental tobacco smoke and lung cancer in female lifetime nonsmokers was evaluated using data collected during the first 3 years of an ongoing case-control study. This large, multicenter, population-based study was designed to minimize some of the methodological problems which have been of concern in previous studies of environmental tobacco smoke and lung cancer. Both a cancer control group and a population control group were selected in order to evaluate recall bias. A uniform histopathological review of diagnostic material was conducted for case confirmation and detailed classification. Biochemical determination of current exposure to tobacco and screening of multiple sources of information to determine lifetime nonuse were utilized to minimize misclassification of smokers as nonsmokers. A 30% increased risk of lung cancer was associated with exposure to environmental tobacco smoke from a spouse, and a 50% increase was observed for adenocarcinoma of the lung. A statistically significant positive trend in risk was observed as pack-years of exposure from a spouse increased, reaching a relative risk of 1.7 for pulmonary adenocarcinoma with exposures of 80 or more pack-years. The predominant cell type of the reviewed, eligible lung cancer cases was adenocarcinoma (78%). Results were very similar when cases were compared to each control group and when separate analyses were conducted for surrogate and personal respondents. Other adult-life exposures in household, occupational, and social settings were each associated with a 40-60% increased risk of adenocarcinoma of the lung. No association was found between risk of any type of lung cancer and childhood exposures from a father, mother, or other household members.

Maternal exposure to N-nitrosatable drugs as a risk factor for childhood brain tumours.

BACKGROUND: Animal models suggest that compounds containing a nitrosyl group (N-nitroso compounds (NNO)) can act as potent transplacental carcinogens. Many common drug formulations have the potential to undergo nitrosation in vivo. The association between maternal use of nitrosatable drugs during pregnancy and development of brain tumours in the offspring was examined in a SEER-based case-control study. METHODS: Maternal exposure to nitrosatable drugs during pregnancy was compared among 361 childhood brain tumour cases and 1083 matched controls recruited through random-digit dialing. RESULTS: There was no increase in risk observed for childhood brain tumours overall (OR = 1.15; 95% CI: 0.69-1.94) or for astrocytomas individually (OR = 1.16; 95% CI: 0.50-2.69). A slight elevation in risk was noted for medulloblastomas (OR = 1.47; 95% CI: 0.28-7.62) and 'other' tumours (OR = 1.27; 95% CI: 0.56-2.86), however, both estimates were based on small numbers. CONCLUSIONS: Our findings suggest that no increased risk of childhood brain tumours was associated with maternal exposure to nitrosatable drugs. The study results should be viewed with caution given the imprecision of the point estimates as well as the lack of data on specific timing and dosage of exposure and degree of nitrosatability of drugs taken.

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.

Short wavelength automated perimetry and tamoxifen use.

BACKGROUND/AIMS: Oestrogen receptors (ORs) have been reported to be present in the retina, and the selective oestrogen receptor modulator tamoxifen has been reported to affect colour vision. This study aimed, therefore, to determine whether standard doses of tamoxifen affect visual sensitivities mediated via short wavelength sensitive (SWS) cones. METHODS: Two types of visual fields were measured for middle aged women who were being treated with 20 mg of tamoxifen daily as adjuvant therapy for early stage breast cancer. Visual fields were measured using short wavelength automated perimetry (SWAP) and frequency doubling perimetry (FDP). For SWAP, 24-2 visual fields were analysed. No subjects had tamoxifen retinopathy or other eye disease. For each type of visual field, mean deviations (MDs) were assessed as a function of the duration of tamoxifen use, using a cross sectional design. In addition, the difference between the two types of MDs was computed after standardisation of each type of MD separately, and this difference itself was evaluated as a function of the duration of tamoxifen use. Duration dependent changes for SWAP were further evaluated as a function of eccentricity within the visual field, and the visual field data were compared with foveal data obtained psychophysically. RESULTS: SWAP sensitivities depended on the duration of tamoxifen use. Subjects who used tamoxifen for about 2 years or less were significantly more likely than subjects who had longer use to have high MDs. The difference between the standardised SWAP and FDP MDs likewise was significantly related to the duration of use, whereas duration of use effects for FDP itself were reduced or absent. Although the duration of use effect observed for SWAP was strongest in the peripheral portion of the visual field, there was evidence of changes in SWS cone mediated vision even at the fovea. CONCLUSION: Standard dosages of tamoxifen can affect SWAP visual fields. The effects of tamoxifen are not equivalent for SWAP and FDP, indicating that tamoxifen affects some types of visual pathways preferentially or selectively. SWS cone pathways, in particular, are affected. SWAP appears able to reveal effects of tamoxifen occurring years before completion of the standard 5 year regimen of use.