Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.

BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Hormonal risk factors and invasive epithelial ovarian cancer risk by parity.

BACKGROUND: Recent studies have suggested that several ovarian cancer risk factors differ by parity status, but these findings have not been confirmed. We evaluated whether known risk factors of ovarian cancer differ between nulliparous and parous women using data from two large prospective cohorts. METHODS: Data from the National Institutes of Health-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were combined for this analysis. Cox regression models were used to estimate associations with ovarian cancer risk. Risk heterogeneity by parity status was assessed using likelihood-ratio tests. RESULTS: Among the 125 437 women included in the analysis, there were 16 589 (13%) nulliparous women and 108 848 (87%) parous women. Of the 623 women diagnosed with invasive epithelial ovarian cancer, 102 (16%) were nulliparous and 521 (84%) were parous. While parity reduced ovarian cancer risk, no differences were found for other risk factors by parity. Among ever users of hormone therapy, body mass index suggestively increased the risk of ovarian cancer by 1.5-fold in nulliparous but not parous women (P-heterogeneity=0.08). CONCLUSION: While nulliparous women have higher ovarian cancer risk than parous women, our findings suggest that the relative effects of most other risk factors do not differ by parity.

The APCI1307K allele and cancer risk in a community-based study of Ashkenazi Jews.

Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer (CRC). APC is a tumour-suppressor gene, and somatic loss occurs in tumours. The germline T-to-A transversion responsible for the APC I1307K allele converts the wild-type sequence to a homopolymer tract (A8) that is genetically unstable and prone to somatic mutation. The I1307K allele was found in 6.1% of unselected Ashkenazi Jews and higher proportions of Ashkenazim with family or personal histories of CRC (ref. 2). To evaluate the role of I1307K in cancer, we genotyped 5,081 Ashkenazi volunteers in a community survey. Risk of developing colorectal, breast and other cancers were compared between genotyped I1307K carriers and non-carriers and their first-degree relatives.

Residential proximity to industrial facilities and risk of non-Hodgkin lymphoma.

Industrial pollution has been suspected as a cause of non-Hodgkin lymphoma (NHL), based on associations with chemical exposures in occupational studies. We conducted a case-control study of NHL in four SEER regions of the United States, in which residential locations of 864 cases and 684 controls during the 10 years before recruitment were used to characterize proximity to industrial facilities reporting chemical releases to the Environmental Protection Agency's Toxics Release Inventory (TRI). For each of 15 types of industry (by 2-digit SIC code), we evaluated the risk of NHL associated with having lived within 2 miles of a facility, the distance to the nearest facility (miles categories of < or =0.5, >0.5-1.0, >1.0-2.0, >2 [referent]), and the duration of residence within 2miles (years categories of 10, 1-9, 0 [referent]), using logistic regression. Increased risk of NHL was observed in relation to lumber and wood products facilities (SIC 24) for the shortest distance of residential proximity (< or =0.5 mile: odds ratio [OR]=2.2, 95% confidence interval [CI]: 0.4-11.8) or the longest duration (10 years: OR=1.9, 95% CI: 0.8-4.8); the association with lumber facilities was more apparent for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7, 95% CI: 1.0-3.0) than for follicular lymphoma (OR=1.1, 95% CI: 0.5-2.2). We also observed elevated ORs for the chemical (SIC 28, 10 years: OR=1.5, 95% CI: 1.1-2.0), petroleum (SIC 29, 10 years: OR=1.9, 95% CI: 1.0-3.6), rubber/miscellaneous plastics products (SIC 30, < or =0.5mile: OR=2.7, 95% CI: 1.0-7.4), and primary metal (SIC 33, lived within 2miles: OR=1.3, 95% CI: 1.0-1.6) industries; however, patterns of risk were inconsistent between distance and duration metrics. This study does not provide strong evidence that living near manufacturing industries increases NHL risk. However, future studies designed to include greater numbers of persons living near specific types of industries, along with fate-transport modeling of chemical releases, would be informative.

Degreasing and risk of non-Hodgkin lymphoma.

OBJECTIVE: To investigate the relationship between selected solvent-related workplace tasks (degreasing, painting, gluing, stripping paint, staining) and risk of non-Hodgkin lymphoma (NHL). METHODS: We analysed occupational data from a large population-based case-control study of NHL conducted in the USA. For participants reporting occupations with possible exposure to organic solvents, job-specific interview modules were administered to elicit in-depth information on solvent-related workplace tasks and other exposure-related factors (225 cases, 189 controls). Unconditional logistic regression models were fit to calculate odds ratios (ORs) and 95% CI for average frequency, maximal frequency and cumulative number of hours having performed each task. Individuals with jobs rated as unexposed to organic solvents in the workplace (180 cases, 213 controls) were used as a reference group. RESULTS: We observed an increased risk of NHL among subjects in the highest category of maximal degreasing frequency (>520 h/year: OR 2.1, 95% CI 0.9 to 4.9, trend test p = 0.02). We found similar associations for the highest levels of average frequency and, among men, cumulative number of hours. Other solvent-related tasks were not associated with NHL. CONCLUSION: Findings from this case-control analysis of solvent-related tasks suggest that frequent degreasing work may be associated with an elevated risk of NHL.

Occupation/industry and risk of non-Hodgkin's lymphoma in the United States.

AIMS: To identify occupations and industries associated with non-Hodgkin's lymphoma (NHL) in a large population-based, case-control study in the USA. METHODS: Cases (n = 1189) of histologically confirmed malignant NHL ages 20-74 were prospectively identified in four geographic areas covered by the National Cancer Institute SEER Program. Controls (n = 982) were selected from the general population by random digit dialling (<65 years of age) and from residents listed in Medicare files (65-74 years of age). Odds ratios and 95% confidence intervals for occupations and industries were calculated by unconditional logistic regression analyses, adjusting for age, gender, ethnicity and study centre. Further analyses stratified for gender and histological subtype were also performed. RESULTS: Risk of NHL was increased for a few occupations and industries. Several white collar occupations, with no obvious hazardous exposures, had elevated risks, including purchasing agents and buyers, religious workers, physical therapists and information clerks. Occupations with excesses that may have exposures of interest include launderers and ironers, service occupations, food/beverage preparation supervisors, hand packers and packagers, roofing and siding, leather and leather products, transportation by air, nursing and personal care facilities, and specialty outpatient clinics. Significantly decreased risks of NHL were found for a number of occupations and industries including post-secondary teachers and chemical and allied products. CONCLUSIONS: The results of this study suggest that several occupations and industries may alter the risk of NHL. Our results support previously reported increased risks among farmers, printers, medical professionals, electronic workers and leather workers. These findings should be evaluated further in larger studies that have the power to focus on specific exposures and histological subtypes of NHL.

The National Bladder Cancer Study: employment in the chemical industry.

The relationship between bladder cancer employment in the chemical industry was assessed in a study of 2,982 incident cases and 5,782 population controls. There were 190 cases and 369 controls who had ever been employed in the chemical industry [odds ratio (OR) = 1.0; 95% confidence interval (CI) = 0.8, 1.2]. Employment in the production of organic chemicals was associated with a 1.3-fold increased risk among men (95% CI = 0.8, 2.1). Risk increased with duration of employment, reaching an OR of 2.4 for 20 or more years (chi for trend = 1.57; P = .06). Women who had worked in the plastics industry had a 3.3-fold increased bladder cancer risk. Within the plastics and rubber industry, increased risks for bladder cancer were found for men in mixing, filtering, grinding, and other dusty operations (OR = 4.6; 95% CI = 1.0, 20.4) and men in heat-associated operations (OR = 2.8; 95% CI = 0.5, 15.3). A 1.4-fold risk among men in agricultural chemicals was attributable to risks in the pesticides subdivision (OR = 2.3; 95% CI = 0.6, 8.2). Men performing dusty operations (i.e., mixing, filtering, sifting, grinding, and crushing) in any industry had an OR of 1.4 (95% CI = 0.8, 2.7). Despite the large number of study subjects, few statistically significant findings were observed and should be evaluated with consideration of the large number of comparisons made in the analysis. The statistical power of case-control studies to detect risks associated with particular occupational exposures is limited by the small proportion of the population employed in any specific occupation or industry.

Coffee drinking and risk of bladder cancer.

The relationship between coffee drinking and risk of bladder cancer was assessed with the use of data from a case-control study of bladder cancer. Incident cases (2,982) and general population controls (5,782) were interviewed. Overall, the relative risk (RR) of bladder cancer for subjects who had ever drunk coffee was estimated as 1.4 (95% confidence interval = 1.1-1.8). There was no consistent relation between the RR estimate and the current consumption level. Among men who drank coffee, those who drank more than 49 cupfuls of coffee per week had an apparent excess in risk, but women who drank that much had an apparent deficit in risk.

Cancer surveillance series: changing patterns of cutaneous malignant melanoma mortality rates among whites in the United States.

BACKGROUND: Mortality from melanoma among whites is still increasing in the United States. In this study, we describe the changing patterns of melanoma mortality rates among whites by demographic factors and geography and further assess the relationship between the geographic patterns and the UV radiation (UV-B) level. METHODS: Age-adjusted incidence and mortality rates were computed by use of the 1970 U.S. population standard. Annual percent changes of mortality were estimated by fitting regression lines to the logarithm of rates. The relationships between melanoma mortality rates and UV-B level over time were assessed by weighted regressions. All statistical tests were two-sided. RESULTS: From 1950-1954 through 1990-1994, melanoma mortality rates increased by 191% and 84% among males and females, respectively. Mortality rates peaked in the 1930 through 1950 birth cohorts for females and in the 1935 through 1950 birth cohorts for males. In the 1950 through 1969 study period, melanoma mortality rates showed a strong North-South gradient, but the gradient weakened in recent periods. The absolute change in mortality for a 10% increase in UV-B among females decreased from 0.08 additional deaths per 100 000 person-years in 1950-1959 to 0.01 additional deaths in 1990-1995. In contrast, the absolute change in mortality among males showed little change over time; additional deaths increased from 0.11 to 0.12 per 100 000 person-years. CONCLUSIONS: Melanoma mortality in the United States reflects the complex interplay of UV radiation levels in each geographic region, the sun-protection behaviors of each generation of males and females in childhood and adulthood, the geographic mobility of the population, and the risk awareness and early detection.

Occupational risks of bladder cancer in the United States: I. White men.

We examined the relationship between occupation and bladder cancer risk using data obtained from interviews conducted with 2,100 white males with bladder cancer and 3,874 population controls during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. The strongest evidence of increased risk among white men was observed for painters, truck drivers, and drill press operatives. For painters, the overall relative risk was 1.5 [95% confidence intervals (CI) = 1.2-2.0]. Among painters who started working prior to 1930, a significant trend in risk with increasing duration of employment as a painter was apparent; the relative risk for such painters employed 10 or more years was 3.0. For truck drivers and drill press operatives, overall risks were 1.3 (CI = 1.1-1.4) and 1.4 (CI = 0.9-2.1), respectively. We observed a significant, positive trend in risk with increasing duration of employment in each of these occupations, with relative risks peaking at approximately two for long-term workers. Excess risks were also observed for workers in several other occupations. In all, we estimate that 21%-25% of bladder cancer diagnosed among white men in the United States is attributable to occupational exposures.

Recent trends in cutaneous melanoma incidence among whites in the United States.

BACKGROUND: It is not yet clear whether increasing melanoma incidence is real or whether recent incidence trends mainly reflect improved diagnosis. To address this question, we examined the most recent melanoma incidence patterns among the white population stratified by sex, age, tumor stage, and tumor thickness by use of data from the Surveillance, Epidemiology, and End Results Program. METHODS: We examined log-transformed age-specific rates for melanoma by 5-year age groups and time periods by year of diagnosis and birth cohort. Melanoma trends were further examined among broader age groups (<40 years, 40-59 years, and > or =60 years) by tumor stage and tumor thickness. Rates were age-adjusted to the 1970 U.S. standard population, and trends were tested by use of a two-sided Student's t test. RESULTS: Melanoma incidence increased in females born since the 1960s. From 1974-1975 through 1988-1989, upward trends for the incidence of localized tumors and downward trends for the incidence of distant-stage tumors occurred in the age group under 40 years. In the more recent time period, 1990-1991 through 1996-1997, age specific rates among females compared with males generally remained stable or declined more for distant-stage tumors and increased less for local-stage tumors. Thin tumors (<1 mm) increased statistically significantly in all age groups (P<.05 for all), except in men under age 40 years. In contrast, rates for thick tumors (> or =4 mm) increased statistically significantly (P =.0003) only in males aged 60 years and older. CONCLUSION: Melanoma incidence may well continue to rise in the United States, at least until the majority of the current population in the middle-age groups becomes the oldest population. The recent trends may reflect increased sunlight exposure.

Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/Cancer Study Group.

BACKGROUND: In recent years, brain lymphoma incidence has dramatically increased, presumably because of elevated risk of brain lymphoma among persons with acquired immunodeficiency syndrome (AIDS). PURPOSE: The objective of this study was to estimate independent incidence and survival rates of brain lymphoma among persons with or without AIDS and to understand the epidemiologic features of this cancer. METHODS: We linked AIDS and cancer registry reports at nine state and local health departments and compared the demographics, histology, and survival of brain lymphoma cases among persons with or without AIDS. The data were limited to people under 70 years of age. We calculated the incidence of brain lymphoma among persons with AIDS and compared observed cases with those expected. The differences were statistically analyzed using the Poisson test. Epidemiologic features of brain lymphoma in persons with or without AIDS were compared using the chi-squared test, the Student's t test, and the chi-squared test for linear trend. The logrank test was used to compare survival rates estimated by the Kaplan-Meier technique. All P values were two-sided. RESULTS: We matched 50,989 AIDS registry reports to 859,398 cancer registry reports (data from 1981 to 1990) and found 431 people with both AIDS and brain lymphoma. Among people with AIDS, those developing brain lymphoma versus those without brain lymphoma were more likely to be white (70% versus 59%; P < .001) and had homosexuality as their only human immunodeficiency virus risk factor (75% versus 64%; P < .001). Of the 431 patients, 223 developed brain lymphomas during 47,465 person-years of observation after diagnosis of AIDS. The absolute incidence rate of brain lymphoma among persons with AIDS was 4.7/1000 person-years (95% confidence interval = 4.1-5.3/1000 person-years), 3600-fold higher than the base-line rate in the general population. From 1980 through 1989, overall counts of brain lymphoma increased ninefold. Most of this increase was derived from persons with AIDS, but a substantial increase also occurred among persons without AIDS (0.04/100,000 in 1982 to 0.28/100,000 in 1989) (chi-squared test for trend; P < .05). The median survival was shortest for persons with AIDS and brain lymphoma (2 months), was intermediate for persons with brain lymphoma without AIDS (5-7 months), and was longest for persons with AIDS without brain lymphoma (14 months) (P < .05 for all comparisons). CONCLUSIONS: This analysis distinguishes the separate epidemiologies of brain lymphoma incidence among persons with or without AIDS and shows brain lymphoma incidence among persons with AIDS to be several thousand-fold higher than that in the general population. The study documents the overwhelming effect of AIDS-associated brain lymphoma on the overall rate in the general population and demonstrates a significantly rising trend, although of a lesser magnitude, among persons without AIDS. IMPLICATIONS: This study emphasizes a greater need to bring health care resources to this burgeoning epidemic.

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

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.

Changing cigarette habits and bladder cancer risk: a case-control study.

With the use of data from the 8,764 subjects in the National Bladder Cancer Study, the separate contribution of various aspects of a person's cigarette smoking history to his increased risk of bladder cancer was estimated. These estimates have not been previously available, owing to the smaller sizes of earlier studies. Our data indicated that people who have only smoked unfiltered cigarettes have higher risks than those who have only smoked filtered cigarettes but that people who have switched from unfiltered to filtered have experienced no reduction in risk. Our data also indicated that smoking cessation substantially reduced the risk. The former smoker appeared to benefit both because he stopped adding to the burden of irreversible damage and because he ceased being exposed to some reversible hazard. Thus the former smoker had a lower risk than the current smoker even though they had smoked the same number of cigarettes daily for the same number of years, but the former smoker's risk remained higher than the risk of a person who never smoked. Our data suggest that one-half of the bladder cancer occurring among men in the United States and one-third of that among women is caused by cigarette smoking.

Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Studies of survival following breast and ovarian cancers in BRCA1 and/or BRCA2 mutation carriers have yielded conflicting results. We undertook an analysis of a community-based study of Ashkenazi Jews to investigate the effect of three founder mutations in BRCA1 and BRCA2 on survival among patients with breast or ovarian cancer. METHODS: We collected blood samples and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (single nucleotide insertion) mutations in BRCA1 and the 6174delT (single nucleotide deletion) mutation in BRCA2. To estimate survival differences in the affected relatives according to their BRCA1 and/or BRCA2 mutation carrier status, we devised and applied a novel extension of the kin-cohort method. RESULTS: Fifty mutation carriers reported that 58 of their first-degree relatives had been diagnosed with breast cancer and 10 with ovarian cancer; 907 noncarriers reported 979 first-degree relatives with breast cancer and 116 with ovarian cancer. Kaplan-Meier estimates of median survival after breast cancer were 16 years (95% confidence interval [CI] = 11-40) in the relatives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarriers, a difference that was not statistically significant (two-sided P = .87). There was also no difference in survival times among the 126 first-degree relatives with ovarian cancer. We found no survival difference between patients with breast or ovarian cancer who were inferred carriers of BRCA1 and/or BRCA2 mutations and noncarriers. CONCLUSIONS: Carriers of BRCA1 and BRCA2 mutations appeared to have neither better nor worse survival prognosis.

Unexplained excess risk of bladder cancer in men.

In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women. We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors. The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9. Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7. Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors.

Multiple births and risk of epithelial ovarian cancer.

BACKGROUND AND METHODS: Prevailing hypotheses about the causes of ovarian carcinogenesis predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of epithelial ovarian cancer. However, the scant available evidence suggests that they may actually be at lower risk. To resolve this issue, we pooled data from eight studies involving 2859 parous women with epithelial ovarian cancer (case patients) and 7434 parous women without ovarian cancer (control women). In addition to assessing their history of multiple births (and the sex of the children, where available), we obtained information on age, parity, oral contraceptive use, and other reproductive factors for each woman. Details of tumor histology were available for all case patients. We estimated the relative risks of various histologic types of ovarian cancers associated with multiple births by using multivariable logistic regression analysis, adjusting for matching and confounding variables. RESULTS: Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%) had a history of multiple births. The adjusted summary odds ratio (OR) for developing all types of epithelial ovarian cancer that are associated with multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no evidence that risks associated with multiple births differed among women with borderline or invasive tumors and among women with same-sex and opposite-sex offspring from multiple births. The risk reductions appeared specific for nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]); in contrast, associations with mucinous tumors (n = 406) were heterogeneous across studies. CONCLUSIONS: Parous women with nonmucinous ovarian cancer are no more likely to have a history of multiple births than other parous women, counter to the predictions of current hypotheses for causes of ovarian cancer.

Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence.

The incidence of non-Hodgkin's lymphoma among white men in the United States was measured as 6.9/100,000 person-years in 1947-1950 and as 17.4 in 1984-1988. We have estimated how much the known and suspected diagnostic and risk factors might have contributed to this apparent increase of 152%. Firm conclusions cannot be drawn without more data on risk and changes in prevalence, but a reasonable range of impacts can be constructed. After accounting for the likely effects of misdiagnosis of Hodgkin's disease as non-Hodgkin's lymphoma, of the acceptance of new entities of non-Hodgkin's lymphoma, of familial factors, of human immunodeficiency virus and other immunosuppressive conditions or drugs, and of occupation, we estimate that the percentage increase in incidence was still 80% among all males and 42% among those aged 0-64. An agent carrying a relative risk of 2.0 rising in prevalence from 0 to 42% would account for the latter rise. Diet, hair dyes, and general environmental exposures to pesticides may be contributing, but currently estimated risks and changes in exposure levels do not appear large enough to account for the residual rise. Among men aged 75-84, some of the residual rise of 109% probably is diagnostic, but only further research will clarify the issue.

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.