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.

Determinants of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in house dust samples from four areas of the United States.

Determinants of levels of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in dust in U.S. homes are not well characterized. We conducted a pilot study to evaluate the relationship between concentrations of PCDD/F in house dust and residential proximity to known sources, including industrial facilities and traffic. Samples from vacuum bag dust from homes of 40 residents of Detroit, Los Angeles, Seattle, or Iowa who participated in a population-based case-control study of non-Hodgkin lymphoma conducted in 1998-2000 were analyzed using high resolution gas chromatography/high resolution mass spectrometry for 7 PCDD and 10 PCDF congeners considered toxic by the U.S. Environmental Protection Agency (EPA). Locations of 10 types of PCDD/F-emitting facilities were obtained from the EPA; however only 4 types were located near study homes (non-hazardous waste cement kilns, coal-fired power plants, sewage sludge incinerators, and medical waste incinerators). Relationships between concentrations of each PCDD/F and proximity to industrial facilities, freight routes, and major roads were evaluated using separate multivariate regression models for each congener. The median (inter-quartile range [IQR]) toxic equivalence (TEQ) concentration of these congeners in the house dust was 20.3 pg/g (IQR=14.3, 32.7). Homes within 3 or 5 km of a cement kiln had 2 to 9-fold higher concentrations of 5 PCDD and 5 PCDF (p<0.1 in each model). Proximity to freight routes and major roads was associated with elevated concentrations of 1 PCDD and 8 PCDF. Higher concentrations of certain PCDD/F in homes near cement kilns, freight routes, and major roads suggest that these outdoor sources are contributing to indoor environmental exposures. Further study of the contribution of these sources and other facility types to total PCDD/F exposure in a larger number of homes is warranted.

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.

Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case-control study.

Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence interval=0.5-1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend=0.23 and 0.26, respectively).

The effect of atopy, childhood crowding, and other immune-related factors on non-Hodgkin lymphoma risk.

OBJECTIVE: Since adult immune responsiveness is influenced by early childhood exposures, we examined the role of family size, history of atopic disease, and other childhood immune-related exposures in a multi-center case-control study of NHL. METHODS: Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Medicare files database. Multivariable logistic regression was used to estimate risk. RESULTS: A history of any allergy (excluding drug allergies), decreased risk of all NHL (Odds Ratio [OR] = 0.7, 95% Confidence Interval [CI] = 0.6-1.0), diffuse large B-cell lymphoma [DLBCL] (OR = 0.6, 95% CI = 0.4-0.9), and follicular NHL (OR = 0.7, 95 CI = 0.5, 1.0). A similar effect was observed for hay fever. A history of eczema was associated with an increased risk of follicular lymphoma (OR = 1.9, 95% CI = 1.1-3.4), but not DLBCL (OR = 1.1, 95% CI = 0.6-2.0). Asthma did not affect risk. Youngest compared to oldest siblings had a 90% increased risk of DLBCL (95% CI = 1.2-3.1; p for trend with increasing birth order = 0.006), but not follicular lymphoma (OR = 1.1, 95% CI = 0.6-1.8). CONCLUSIONS: We infer that some childhood and immune-related factors may alter NHL risk.

Mortality in women given diethylstilbestrol during pregnancy.

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI = 1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03-1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES-cohort interaction was not significant (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses.

Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000.

The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B2, B6, and B12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B6 and methionine, may be protective against NHL.

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States).

OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. METHODS: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. CONCLUSIONS: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi Study.

When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401-1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but has little or no effect on the carriers.

Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.

BACKGROUND: Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS: We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS: Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS: The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

Age at natural menopause and the risk of epithelial ovarian cancer.

OBJECTIVE: To investigate the relationship between age at natural menopause and risk of developing epithelial ovarian cancer. METHODS: Using data from six population-based, case-control studies conducted in the United States, age at natural menopause among 1411 women with epithelial ovarian cancer and 6380 control subjects were analyzed using survival analysis methods, including Kaplan-Meier and proportional hazards models. Subjects ranged from 20 to 81 years of age. RESULTS: The median age at natural menopause was 50 years among cases compared with 51 years among controls, a difference of borderline statistical significance (P =.06). The hazard ratio for the relationship between case-control status and age at natural menopause was 1.09 (95% confidence interval 0.99, 1.20). Controlling for potential confounders including parity, oral contraceptive use, tubal ligation, smoking, and body mass index did not appreciably change this association. There was little evidence of an association between early age at natural menopause and early onset ovarian cancer (diagnosis age under 48 years). CONCLUSION: We observed a weak association between ovarian cancer risk and age at natural menopause and, among women with early onset disease, there was little evidence to suggest that early menopause is related to ovarian cancer. Thus, there seems little need for increased surveillance or screening for ovarian cancer among women with early natural menopause.

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.

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy.

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

Epidemiologic tools for today and tomorrow.

As the premier population sciences, epidemiology and demography face common challenges as the U.S. population ages, as the genomic revolution unfolds, and as computing power changes the scale of analysis by several orders of magnitude. Each discipline does need to develop new tools to address the changing research questions, and the best strategy for success includes increased collaboration between the disciplines. The paradigms of each discipline still offer important insights into the problems of both disciplines, so cross-training would be a simple step to begin enlarging the tool box for population science.

Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors: preliminary data from the prostate, lung, colon, and ovarian cancer screening trial.

OBJECTIVE: We assessed whether asymptomatic ovarian abnormalities detected on ultrasonography in postmenopausal women are precursors to ovarian cancer. STUDY DESIGN: We compared the transvaginal ultrasonographic findings from the initial examination of 20,000 postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening with data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suggestive characteristic(s) of a septum, a solid component, or an irregular or thick wall ("complex cysts") from simple sonolucent cysts with none of those features. RESULTS: High parity, a strong ovarian cancer protective factor, was negatively associated with complex cysts (odds ratio for > or =5 births vs no births, 0.72; 95% confidence interval, 0.53-0.97), but long-term oral contraceptive use, another strong ovarian cancer protective factor, was not associated with complex cysts (odds ratio, 0.96; 95% confidence interval, 0.76-1.20). A family history of ovarian cancer or multiple breast cancers, a strong risk factor for cancer, was not associated with complex cysts (odds ratio, 0.99; 95% confidence interval, 0.68-1.44). Other abnormalities found on ultrasonography (including simple cysts, bilateral cysts, or all abnormalities combined) also did not share the established risk factors for ovarian malignancy. We did not identify any combination of features of abnormalities (septum, echogenicity, size, or papillary projections) that manifested the cancer risk factor profile. CONCLUSIONS: Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasonography are determined to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer. The eventual identification of such precursors will yield opportunities for earlier diagnosis, screening of high-risk groups, and better understanding of the cause of this often lethal malignancy.