Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder.

Recent incidence data from the United States indicate that transitional cell carcinoma accounts for the vast majority (95%) of bladder tumors in this country, with squamous cell carcinoma (less than 3%) and adenocarcinoma (less than 2%) comprising nearly all the remaining cases. Rates of squamous cell carcinoma and adenocarcinoma were higher in blacks compared to whites, while the reverse was true for transitional cell carcinoma. All three tumors predominated in males, especially transitional cell carcinoma. A population-based case-control study of bladder cancer conducted in 10 geographical areas of the United States identified 43 patients with squamous cell carcinoma and 32 with adenocarcinoma to permit an examination of risk factors. Cigarette smoking was significantly associated with risk of squamous cell carcinoma, with the relative risk rising to 6.1 among smokers of 40 or more cigarettes/day. Significantly elevated risks of squamous cell carcinoma were also associated with a history of 3 or more urinary tract infections (relative risk = 5.7) and with employment as welders and cooks. Risk factors were generally less conspicuous for adenocarcinoma, except for a significant trend with the amount of coffee drinking; however, this finding is based on small numbers and should be interpreted cautiously.

Follow-up study of twenty-four families with Li-Fraumeni syndrome.

The Li-Fraumeni cancer family syndrome is manifested by susceptibility to breast cancer, sarcomas, and other neoplasms in children and young adults. The present study utilized clinical follow-up data on 545 members of 24 Li-Fraumeni kindreds living and cancer-free at family ascertainment. Two hypotheses were tested based on a model of autosomal dominant genetic predisposition: (a) that syndrome cancers would continue to occur excessively during follow-up compared to the general population, and (b) that the tumors would occur primarily among those family members likely to carry the gene. Population cancer rates were compared with cancer rates in follow-up of the cohort from ascertainment to 1988. Risk of carrying the gene for the syndrome at the time of ascertainment was calculated for each family member under two models with somewhat different definitions of affection with the syndrome. Cancer occurrence after ascertainment was then analyzed according to the risks. Cancer did continue to occur excessively among the entire cohort during follow-up [relative risk (RR 2.1)]. The excess was greatest below age 20 (RR 21.1), declined with increasing age, and was most pronounced for neoplasms featured in the syndrome (RR 18.2). Among persons less than age 45, at least 87% of cancers occurred in those at higher risk of carrying the gene under both genetic models (RR 22.9 and 21.3). The clinical data, therefore, reliably identify individuals likely to carry a dominantly inherited gene conferring susceptibility to a specific constellation of neoplasms. Recent identification of a germ line mutation in the tumor suppressor gene p53 in persons with the syndrome may, if confirmed, have implications for ultimately defining the component tumors of the syndrome and for the causes and prevention of those tumors arising outside these families.

HLA antigens in renal cell carcinoma.

HLA antigen type was studied in 35 renal cell carcinoma patients who had bilateral disease, an early age of onset (less than age 45), or a family history of kidney cancer. Increased frequencies of the single-locus antigens HLA-DR8 (relative risk, 3.3) and HLA-Bw44 (relative risk, 2.1) and a deficit of HLA-DR1 (relative risk, 0.4) were found. Although based on small numbers, the relative excess was highest among persons phenotypically HLA-Bw44DR8. A higher frequency of the three-locus phenotype HLA-A3B7DR2 was also noted. The unusual HLA patterns were most pronounced among patients of German or Scandinavian origin, population groups reported to have an elevated risk of renal cancer.

Hypertension in long-term survivors of childhood renal cancers.

The prevalence of hypertension was investigated in 119 adults who have survived for up to 53 years following the diagnosis of renal cancer in childhood (Wilms' tumor, 116 patients; renal carcinoma, three patients). Twenty-four (20%) have developed definite or borderline hypertension, as compared with 18.1 cases expected based on US population rates (relative risk [RR], 1.3; 95% confidence interval [CI], 0.9 to 2.0; P = .20). This nonsignificant excess is due to the heightened prevalence of definite hypertension among one subgroup of male patients. The findings are not explained by cigarette smoking, obesity, age, and stage at diagnosis of Wilms' tumor, or family history of hypertension. A case-comparison analysis within the cohort showed no consistent hypertensive effect associated with radiation therapy dose, radiotherapy concurrent with dactinomycin chemotherapy, or extent of renal surgery. Hypertension is not a common late complication of Wilms' tumor in our patients.

Tuberculosis chemotherapy and risk of bladder cancer.

In a population-based study of 2982 bladder cancer patients and 5782 population controls from 10 geographical areas of the US, no excess risk was associated with medications used for tuberculosis treatment or prophylaxis (relative risk (RR) = 0.95). The findings agree with other epidemiological studies that have not confirmed earlier reports linking isoniazid (INH) exposure to bladder cancer.

Occupations of fathers of patients with Wilms's tumour.

A case-control study of 149 Connecticut-born children with Wilms's tumour reported to the Connecticut Tumor Registry during the period 1935--1973 and of 149 matched controls was undertaken in order to explore the possibility that children with Wilms's tumour may have been exposed perinatally to carcinogenic agents. The occupation of the father at the time of the child's birth was investigated and used as an indicator of potential sources of carcinogens to which infants in the study may have been exposed. An association was found between paternal occupations related to lead in the group developing Wilms's tumour compared with the controls.

Estimation of HLA phenotype frequencies from two- and three-locus haplotype frequencies.

A procedure for estimating HLA phenotype frequencies from two- and three-locus haplotype frequencies is described. Formulae for this procedure are derived, and examples are presented to illustrate the application. The procedure is useful when multiple-locus phenotype frequencies from a laboratory control series are not available, or when a sufficiently large number of laboratory controls have not yet been typed for recently defined antigens or loci to yield stable multiple-locus rates for comparative purposes.

Second cancer following cancer of the urinary system in Connecticut, 1935-82.

The risk of second primary cancer was assessed in persons who developed cancer of the urinary tract in Connecticut during 1935-82. Among 12,384 patients with a first primary tumor of the bladder or urethra, a second cancer was reported in 1,151 (or 9%). A significantly elevated relative risk (RR) of 1.23 was due to excess cancers of the lung, larynx, prostate, and kidney, and acute nonlymphocytic leukemia. Among 5,115 persons with a first primary tumor of the kidney, renal pelvis or ureter, a second cancer was reported in 374 (or 7%) that yielded a significantly elevated RR of 1.54 due to excess tumors of the bladder and prostate and second primary kidney neoplasms. The role of common etiologic factors, such as cigarette smoking, the multifocal tendency of tumors of the urinary tract, and heightened medical surveillance are discussed in relation to these findings.

Familial and environmental interactions in bladder cancer risk.

In a population-based study of 2,982 bladder cancer patients and 5,782 controls in 10 geographic areas of the United States which was designed to assess the role of environmental risk factors, information was also obtained on the history of urinary tract cancer in first-degree relatives. A family history of urinary tract cancer significantly elevated the risk of bladder cancer [relative risk (RR) = 1.45], with higher risks observed among patients under age 45. The risks of bladder cancer associated with positive family history were generally higher among persons with suspected environmental exposures, particularly heavy cigarette smoking (RR = 10.7 among those who smoked 3 or more packs per day). Further studies of bladder cancer should incorporate biochemical and genetic probes to assess mechanisms of familial susceptibility and interactions with environmental factors.

Second cancer following cancer of the digestive system in Connecticut, 1935-82.

The risk of developing a second primary cancer was evaluated in approximately 64,000 persons diagnosed with cancer of the digestive system in Connecticut during 1935-82. Significant excesses of all second cancers combined were observed following cancer of the esophagus (58 observed vs. 33 expected), small intestine (41 vs. 24), and colon (2,268 vs. 1,714). A slight excess of multiple primaries was observed following cancer of the liver and biliary tract (47 vs. 40). The observed number of second cancers was nearly equal to the expected number for persons initially diagnosed with cancers of the stomach (251 vs. 258), rectum (952 vs. 941), and pancreas (40 vs. 40). Persons with initial cancers of the small intestine, colon, and rectum also had excess second cancers arising primarily in the colon, which suggested the influence of common etiologic factors or possibly misclassified metastases in some. Shared dietary, socioeconomic, or hormonal factors may explain the excess of uterine and ovarian cancers among patients with colon cancer and the excess of breast cancer among patients with colon and rectal cancers. Oral and respiratory cancers occurred more frequently than expected in persons with an initial esophageal cancer, which is likely due to common risk factors of cigarette smoking or alcohol intake, or both. The elevations in cancer of the prostate among males with cancers of the esophagus, small intestine, colon, rectum, liver/biliary, and pancreas are probably artifacts associated with increased medical surveillance of cancer patients. The prostate cancer excesses were limited to the first year after diagnosis of the initial cancer or decreased over time for all but cancer of the colon and small intestines. Increased medical surveillance may also contribute to the excess renal and bladder cancers seen within 5 years of diagnosis of stomach cancer. Excesses were also seen for second pancreatic cancer among small intestine and liver/biliary cancer patients and second kidney and brain cancers among those with colon cancer. The deficits of stomach and rectal cancer among persons initially diagnosed with the same tumors, respectively, were anticipated because surgical removal of the organ is the primary form of treatment. Patients with rectal cancer also had deficits of stomach and pancreatic cancers. Future research should clarify the role of diet, alcohol, metabolic and endocrine factors, and host susceptibility on the risk of second neoplasms following cancer of the digestive system.

Risk of second malignancy after cancers of the renal parenchyma, renal pelvis, and ureter.

Risk of second primary malignancy was assessed in a population-based survey of persons who developed cancers of the renal parenchyma, renal pelvis, or ureter in Connecticut during the period 1935-1982. Among 4176 patients with a first primary tumor of the renal parenchyma, a second cancer was reported in 219 (5%), yielding a small but significantly elevated relative risk (RR) of 1.2, which reflects excesses for cancers of the bladder, kidney, and lymphatic-hematopoietic system. Among 939 patients with a first primary tumor of the renal pelvis or ureter, a second cancer was reported in 155 (17%), associated with a significantly elevated RR of 2.7. This resulted mainly from a 21-fold increase in risk for bladder cancer, although significant excesses were also found for lung and prostate cancers, and metachronous cancers of the renal pelvis and ureter. These associations seem to reflect the multicentric behavior of tumors arising in the urinary tract, the role of cigarette smoking, and host factors yet to be defined, and some degree of heightened medical surveillance and detection of tumors, especially in the same organ system.

Childhood cancer in offspring of two Wilms tumor survivors.

A search was made for cancers among offspring and siblings of 149 Connecticut-born children with Wilms tumor reported to the Connecticut Tumor Registry during 1935 to 1973. Nasopharyngeal rhabdomyosarcoma developed in the daughter of a man with unilateral Wilms tumor that also affected his sister. Hodgkin disease developed in the daughter of a woman who had unilateral Wilms tumor. One other patient had a sibling with Wilms tumor and three had a sibling with other cancers (two Hodgkin disease, one testicular seminoma). The survey suggests an excess risk of other forms of cancer among the progeny and siblings of Wilms tumor patients.

Cancer in patients receiving long-term dialysis treatment.

A large excess of non-Hodgkin's lymphoma has been documented in renal transplant patients and may be related to immunosuppressive therapy, persistent antigenic challenge from the graft, or both. To determine whether immuno-suppression resulting from chronic renal failure is associated with an elevated risk of certain tumors such as non-Hodgkin's lymphoma, the authors studied cancer incidence in a national cohort of 28,049 patients in the United States with chronic renal failure who received maintenance dialysis for at least six months (totaling 66,706 person-years of observation). Compared with national incidence rates, the relative risk (RR) of cancer was 0.9 (excluding nonmelanoma skin cancer, multiple myeloma, kidney cancer, and uterine cervix cancer). Moderate excesses of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, thyroid cancer, and biliary tract cancer were found, but were not statistically significant for both sexes combined. A significantly elevated risk of non-Hodgkin's lymphoma among patients with chronic glomerulonephritis (RR = 2.6) accounted for the excess observed in the total series, raising the possibility of factors specific to this disease.

Risk of second malignancy after cutaneous T-cell lymphoma.

Risk of second primary malignancy was assessed in a population-based follow-up survey of all persons who developed cutaneous T-cell lymphoma (CTCL) in nine geographic areas of the United States covered by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute during the period 1973 to 1983. Among 544 patients with a first primary tumor reported as CTCL, a second cancer developed in 35 (6%), yielding a significantly elevated relative risk (RR) of 1.7, which reflects excesses for cancers of the lung and colon and non-Hodgkin's lymphoma. Although the excess of lymphoma may be related to the evolution of CTCL to less differentiated T-cell lymphoma, additional studies are needed to clarify the immunologic, genetic, viral, and environmental factors that may contribute to the development of second cancers.

Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma.

Complete responses lasting from 4 to 14 years were documented in 65 of 331 (20%) patients with cutaneous T cell lymphoma treated with topical mechlorethamine (HN2) between 1968 and 1982. Such long-lasting remissions occurred most often, but not invariably, in patients with patch or plaque phase mycosis fungoides without palpable lymphadenopathy (stage Ia or Ib). The likelihood of a continuous remission was enhanced by initiation of treatment before an unequivocal pathologic diagnosis. Despite the long-lasting responses in these patients, however, relapses have been documented in 11 (17%) of these patients, and all relapses occurred within 8 years of discontinuing maintenance topical chemotherapy. Thus, in our experience, a continuous remission lasting 8 or more years provides evidence that cutaneous T cell lymphoma can be eradicated by aggressive topical chemotherapy. This circumstance was observed in 35 patients, representing a cure rate of at least 11% overall. In addition, when compared with the general population of the United States, patients who received topical HN2 were at an 8.6-fold and a 1.8-fold increased risk for the development of squamous cell carcinoma and enhanced for Hodgkin's disease and colon cancer but not for systemic cancers known to be induced by systemic administration of alkylating drugs. These results compare favorably with experiences with topical HN2 chemotherapy at other centers but raise questions about the risks associated with long-term administration for maintenance of remissions.

Urinary tract infection and risk of bladder cancer.

In an epidemiologic study of 2982 bladder carcinoma patients and 5782 population controls from 10 geographic areas of the United States, the role of urinary tract infection and inflammation in the etiology of this neoplasm was evaluated. A history of urinary tract infection significantly elevated the risk of bladder cancer, particularly in individuals who reported three or more infections (relative risk (RR) = 2.0). Significantly increased bladder cancer risk was also found for bladder stones (RR = 1.8), while kidney stones showed no relation. A history of three or more urinary tract infections was strongly related to squamous cell carcinoma in particular (RR = 4.8).

Associations between bladder cancer risk factors and tumor stage and grade at diagnosis.

Using data on 1,860 bladder cancer cases and 3,934 population-based controls from the National Bladder Cancer Study, we examined associations between suspected bladder cancer risk factors and tumor stage and grade. Employment in a high-risk occupation was associated with the entire clinical spectrum of bladder cancer rather than a particular tumor stage or grade. For example, relative risks (RR) were similar for noninvasive and invasive disease (1.5 and 1.6, respectively). Cigarette smoking also increased risk of the entire clinical spectrum of bladder cancer, but the more advanced the stage, the stronger the effect. For example, relative risks of noninvasive and invasive bladder cancer for current heavy smokers were 3.0 and 5.2, respectively. Cigarette smoking was associated with higher risk of low-grade than high-grade tumors, once stage of disease was taken into account. Compared with whites, nonwhites were at a lower risk of noninvasive bladder cancer (RR = 0.4) but at similar risk of invasive bladder cancer (RR = 1.1), a pattern indicating racial differences in health practices related to bladder cancer detection. History of urinary tract infections and bladder stones was associated with increasing relative risks for advanced tumor stage. Heavy artificial sweetener use was associated with higher-grade, poorly differentiated tumors. Coffee consumption and family history of bladder cancer were not consistently associated with tumor stage or grade. Overall, different clinical presentations of bladder cancer share most suspected bladder cancer risk factors, including employment in a high-risk occupation and cigarette smoking.

Asbestos-associated diseases in a cohort of cigarette-filter workers.

To estimate the effects on health of occupational exposure to crocidolite, a highly toxic form of asbestos, we studied a cohort of 33 men who worked in 1953 in a Massachusetts factory that manufactured cigarette filters containing crocidolite fibers from 1951 to 1957. Twenty-eight of the men have died, as compared with 8.3 deaths expected. This increased mortality was attributable to asbestos-associated diseases. Fifteen deaths were caused by cancer, as compared with 1.8 expected (relative risk, 8.2; 95 percent confidence interval, 4.6 to 13.4), including eight from lung cancer, five from malignant mesothelioma, and two from other types of cancer. There were seven deaths from nonmalignant respiratory disease, as compared with 0.5 expected (relative risk, 14.7; 95 percent confidence interval, 5.9 to 30.3), of which five were due primarily to asbestosis. In contrast, the mortality rates from cardiovascular diseases and all other causes were not increased. Four of the five living workers have pulmonary asbestosis; three of them have recently diagnosed cancers, including two additional lung cancers. We conclude that the extremely high morbidity and mortality in these workers were caused by intense exposure to crocidolite asbestos fibers.

Pregnancy outcome in survivors of advanced Hodgkin disease.

BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease.