Vitamin A and lung cancer.

Retrospective dietary and smoking data were gathered by interview of 292 white male patients with lung cancer and 801 control patients with nonrespiratory, nonneoplastic diseases at Roswell Park Memorial Institute, Buffalo, New York. A computed index of vitamin A intake was used to differentiate lung cancer patients from controls. Lung cancer patients had lower values than did controls. The reduced relative risk (RR) of lung cancer associated with vitamin A was most evident among men who smoked heavily. For them, a dose-response relationship increasing to an RR of 2.4 for low values of the index was observed. Frequency of daily milk drinking was lower among patients with lung cancer. Lower RR was found among the men who smoked heavily and frequently consumed carrots. These findings are consistent with evidence from animal studies on inhibition of tumor incidence by retinoids and with previous findings in prospective and retrospective epidemiologic studies.

A case-control study of dietary and nondietary factors in ovarian cancer.

A case-control study is presented that estimates ovarian cancer risk for various factors, including diet. Data collected by interview between 1957 and 1965 for 274 white women aged 30-79 years with epithelial carcinoma of the ovary are compared to data similarly collected for 1,034 hospital controls. Relative risk estimates are presented for the total group as well as for premonopausal (ages 30-49) and postmenopausal (ages 50-79) are groups. In the total group, cancer risk increased with increasing age at first marriage (P less than .01) and previous history of benign breast disease (P less than 0.1), and risk decreased with increasing number of previous pregnancies (P less than .01). In the 50- to 79-year age group, a marginally significant trend for decreasing risk with increasing obesity was observed (P less than .10). There was no significant risk (i.e., P less than .10) associated with the consumption of alcohol, cigarettes, coffee, tea, total dietary protein, vitamin C, or fat at any age. In the 30- to 49-year age group only, increased risk (P less than .01) was seen in women reporting diets low in fiber and vitamin A from fruit and vegetable sources. Multiple regression analysis demonstrated that the apparent protective effect of vitamin A in the 30- to 49-year age group (but not dietary fiber) was independent of the nondietary factors analyzed in this study (P less than .05).

Diet in the epidemiology of carcinoma of the prostate gland.

In vivo, in vitro, prospective, and retrospective epidemiologic inquiries have suggested that retinoids inhibit cancer, and fats have been hypothesized to enhance and ascorbic acid to reduce cancer risk. Comparison of 260 patients from Buffalo with cancer of the prostate gland was made with two different control series of similar size and age distribution. Regardless of the control group, risk of prostate cancer gained with increases in ingestion of retinoids, animal fats, and vitamin C. These anomalous findings may be due to peculiarities in methodology. From the possible specificity of effect of the nutrients studied, as shown in experimental animals and in vitro, a hypothesis could be made that a substance like vitamin A or C, which may inhibit certain cancers, also may enhance risk of other cancer types or have neither effect.

p53 mutations in bladder tumors from arylamine-exposed workers.

In this study we compared the frequency and pattern of p53 mutations in 34 bladder tumors from people with high-level occupational exposure to arylamines to those in 30 bladder tumors from people without such exposure. No differences were observed for p53 mutations between the two groups. The frequency of mutation was similar at 47% for arylamine-exposed individuals and 53% for unexposed individuals and showed a similar pattern of mutation, with GC to AT transitions accounting for the majority of the mutations in both groups. This finding suggests that arylamine exposure does not leave a mutational "footprint" in the p53 gene. However, compared to other tumors, bladder tumors from both exposed and unexposed individuals had a high frequency of multiple mutations and it is interesting that these mutations were highly concordant. We suggest that one explanation of this pattern of mutations could be from decreased DNA repair fidelity within tumor cells. The frequency of mutation in p53 is closely linked to tumor grade and stage and so may be a late event in the development of bladder tumors.

Regular use of analgesic drugs and ovarian cancer risk.

Analgesics have been shown to reduce risk for colorectal cancer. Results from three recent reports (D. W. Cramer et al., Lancet, 351: 104-107, 1998; C. Rodriguez et. al., Lancet, 352: 1354-1355, 1998; L. Rosenberg et al., Cancer Epidemiol. Biomark. Prev., 9: 933-937, 2000) suggest that these drugs might be associated with decreased risk for ovarian cancer. In this hospital-based case-control study, we compared 547 patients with ovarian cancer to 1094 age-matched patients with nonneoplastic conditions. All of the participants received treatment at the Roswell Park Cancer Institute between 1982 and 1998 and completed a comprehensive epidemiological questionnaire that included information on demographics, life-style factors, and reproductive characteristics as well as frequency and duration of aspirin and acetaminophen use. Women who reported that they had used one or more of these agents at least once a week for at least 6 months were classified as analgesic users. Logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Aspirin users were not at reduced risk of ovarian cancer compared with nonusers (adjusted OR, 1.00; CI, 0.73-1.39). There was also no evidence of a decrease in risk as a function of greater frequency of use or prolonged duration of use. Regular acetaminophen use was associated with a reduced risk (adjusted OR, 0.56; 95% CI, 0.34-0.86), and risk reductions were observed for women with the greatest frequency of use (adjusted OR, 0.32; 95% CI, 0.09-1.08) and longest duration of use (adjusted OR, 0.51; 95% CI, 0.27-0.97). These data suggest that regular use of acetaminophen, but not aspirin, may be associated with lower risk of ovarian cancer.

Familial and nutritional risk factors for p53 overexpression in colorectal cancer.

Although familial and dietary factors are recognized as important risk determinants for colorectal tumorigenesis, the specific causes of colorectal cancer remain unclear. Studies of p53 genetic alterations have provided clues concerning the etiology of many cancers. This study was designed to determine whether overexpression of the p53 protein is associated with familial and dietary risk factors. Epidemiological data were obtained from 163 colorectal cancer cases and 326 healthy controls. Tumors of all patients were analyzed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Of patient tumors, 44.8% showed p53 nuclear reactivity. Colorectal cases versus controls were three times more likely to report a family history of colorectal cancer [odds ratio (OR), 3.12; 95% confidence interval (CI), 1.77-5.52]. Only cruciferous vegetables exhibited a significant inverse association (OR, 0.59; 95% CI, 0.34-1.02; trend test, P = 0.03) for the highest versus lowest quartiles. Both meat and beef displayed an elevated increase in risk. When cases with p53 overexpression (p53 positive) were compared with cases without p53 overexpression (p53 negative), etiological heterogeneity was suggested for family history of colorectal cancer (OR, 0.39; 95% CI, 0.16-0.93), cruciferous vegetables (trend test, P = 0.12), and beef consumption (trend test, P = 0.08). To estimate the individual relative risks for p53-dependent and p53-independent pathways, each p53 subtype was compared with controls. Cruciferous vegetables exhibited a significant association (OR, 0.37; 95% CI, 0.17-0.82; trend test, P = 0.03) when p53 positive cases were compared with controls. When p53 negative cases were compared with controls, a significant increase in risk was observed for family history of cancer (OR, 4.46; 95% CI, 2.36-8.43) and beef (OR, 3.17; 95% CI, 1.83-11.28; trend test, P = 0.006). The p53 (positive) dependent pathway was characterized by an inverse association with cruciferous vegetables, and p53-independent tumors were characterized by family history and beef consumption. These data may indicate the significance of linking epidemiology and molecular biology in assessing specific etiological pathways.

Recent developments in the epidemiology of prostate cancer.

The purpose of this review is to examine the implications of recent trends in prostate cancer incidence and mortality and to consider recent progress of epidemiological research on this disease. The incidence and mortality rates for prostate cancer are changing throughout the world at an accelerating pace. Much of the increase in incidence is related to changes in detection technology, but increases in mortality rates suggest other factors are involved. Recent research has focused on race-related difference, diet and related lifestyle exposures, the aetiologic significance of vasectomy and, patterns of familial aggregation. Continued monitoring of trends in incidence and mortality will be important as prostate cancer becomes a greater public health burden worldwide. Epidemiological research has identified several possible risk factors which may be useful for prostate cancer prevention and targeting high-risk individuals for early detection intervention. Additional research may confirm and refine understanding of prostate cancer aetiology.

Epidemiologic evidence of perinatal influence in the etiology of adult cancers.

Using data from 5489 cancer patients and 2647 patients without cancer we investigated whether parental age at the birth of the patient or the patient's rank within his sibship was related to the risk of cancer during adulthood. An increase of 10 years in maternal age was associated with an increase of 24% for the incidence of breast cancer (odds ratio = 1.24%; 95% CI = 1.09-1.41); the corresponding increase for paternal age was 19% (odds ratio = 1.19; 95% CI = 1.07-1.33). There was some evidence that the age of each parent may make an independent contribution to the risk of breast cancer. For certain types of genito-urinary cancers, the risk was higher when the parents were relatively young at the birth of the patient. These cancers included tumors arising in the prostate (odds ratios = 0.71 and 0.55 for maternal and paternal ages, respectively), testis (odds ratios = 0.57 and 0.52), penis (odds ratios = 0.37 and 0.45), kidney (odds ratios = 0.66 and 0.60), and bladder (odds ratio = 0.79 and 0.85). The associations for cancer of the prostate and bladder were stronger among patients who were diagnosed at a relatively young age. No statistically significant effects were found for birth order relative to adult cancers. The authors conclude that environmental factors that affect the parents or that operate in the perinatal period may have stronger influences on the incidence of adult cancers than have been previously recognized.

Cholesterol and cancer in a population of male civil service workers.

Cancer incidence and mortality were ascertained in a cohort of 1910 male participants of the Albany Cardiovascular Health Center (CVHC). The New York State Cancer Registry, vital records files, CVHC follow-up records, New York State Retirement System files, and New York State Department of Motor Vehicles driver's license files were used. Serum cholesterol measurements as well as values for other exposure variables were obtained from records of medical examinations which began in 1953-1954. The study cohort was divided into two groups, based on initial serum cholesterol measurement (less than or equal to 190 mg/100 ml and less than or equal to 190 mg/100 ml). For total cancers, both incidence and mortality were similar in these groups. For digestive cancer, both incidence and mortality were slightly lower in the less than or equal to 190 mg/100 ml group. The deficit was not statistically significant. For respiratory cancer, relative risk and rate ratio estimates were in the range of 1.4-1.7 for incidence and mortality. The excess risk in the less than or equal to 190 mg/100 ml group was of borderline statistical significance. The association was concentrated in the lowest cholesterol quintile rather than suggesting a strong dose-response relationship. The estimates were not found to be confounded by cigarette smoking, body mass index, education or age. A reduction in the crude rate ratio estimate from 1.5 to 1.2 was observed when early cases were excluded, suggesting that part of the observed excess may be due to preclinical cancer.

Impact of screening on prostate cancer rates and trends.

Widespread implementation of prostate cancer screening has affected several epidemiologic features of the disease including incidence, tumor and patient characteristics, patterns of care and outcomes. Some of these changes have been interpreted as evidence of the success of PSA testing as a cancer control strategy. Data are available from multiple sources to assess the association of early detection on recent prostate cancer rates and trends. National mortality data in the United States may be particularly informative because of the early and widespread adoption of PSA testing there. Incidence data from tumor registries and other regional resources are also relevant to this question. Case-control analyses and modeling of relevant rates and trends have recently been reported. Multiple sources of data show that prostate cancer incidence rates rose following the introduction of PSA testing. The average age at diagnosis has fallen, the proportion of advanced stage tumors has declined, the proportion of moderately differentiated tumors has increased, and patterns of care have changed accordingly. A decline in mortality began in the United States in 1991. The decline in mortality is well established but this recent trend may only retrace an increase in mortality that immediately preceded. The descriptive epidemiology of prostate cancer reveals many effects of the introduction of prostate cancer screening. Although the evidence suggests increased prostate cancer testing has yielded public health benefit, this has not yet been shown conclusively.

Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer.

OBJECTIVE: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. METHODS: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, chi2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. RESULTS: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. CONCLUSION: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.

Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study.

OBJECTIVE: To evaluate the role of hormone replacement therapy (HRT) as a risk factor for the development of epithelial ovarian cancer. METHODS: A case-control study was performed that used 491 patients with epithelial ovarian cancer frequency matched for age at diagnosis (+/-5 years) with a control population of 741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, and education. RESULTS: One hundred of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741 patients (21.6%) in the control population had ever used HRT (OR 0.85; 95% confidence interval [CI] 0.62, 1.2). A significant association between HRT and specific histologic subtypes of epithelial ovarian cancer was not demonstrable for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), Clear cell carcinoma (OR 1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A significant association between duration of use of HRT and the risk of developing epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI 0.5, 1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95% CI 0.3, 1.4). CONCLUSION: A significant association between the use of HRT and the risk of developing epithelial ovarian cancer, even with prolonged exposure, is not demonstrable.

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.

Familial Ovarian Cancer Registry.

Ninety-four families totaling 201 cases are reported in this first report of the Familial Ovarian Cancer Registry. The results of the Registry and future studies are presented.

Patterns of care survey data on family history and ulcerative colitis in rectal cancer.

Data from a short-term survey on rectal cancer, sponsored by the Commission on Cancer of the American College of Surgeons, were analyzed in order to assess the association between family history of bowel cancer, ulcerative colitis, and rectal cancer. Overall, 7.4% of rectal cancer patients had a positive family history of bowel cancer and 2.5% reported personal history of ulcerative colitis. The association between these two factors was statistically significant. Patients with a positive family history were significantly younger than those without a family history of bowel cancer. Significantly more white patients than black patients had positive family histories. Significantly greater proportions of patients with earlier stage disease and well differentiated tumors were observed among persons with a family history of bowel cancer. No such association was observed among patients with a history of ulcerative colitis.

Trends in treatment of localized prostate cancer by radical prostatectomy: observations from the Commission on Cancer National Cancer Database, 1985-1990.

OBJECTIVE: Tumor registry data were studied to assess the magnitude and nature of the trend toward increased use of radical prostatectomy for the treatment of newly diagnosed localized prostate cancer. METHODS: The Commission on Cancer of the American College of Surgeons National Cancer Data Base aggregates data from hospital tumor registries located throughout the United States. Data from this resource on 4,531 patients treated in 1985, 25,028 treated in 1988, and 21,697 treated in 1990 were reviewed. RESULTS: The data indicate that selection of radical prostatectomy increased markedly over this interval. Use of radical prostatectomy was greatest in younger men in every year studied. The proportion of patients treated by radical prostatectomy was greatest in the western United States and least in New England and the mid-Atlantic region. Radical prostatectomy was associated with patients' socioeconomic status and race as well as with the hospital's caseload of patients with cancer. CONCLUSIONS: The pattern of care for localized prostate cancer is changing significantly. Further research is needed to assess whether these variations reflect differences in access to care or patterns of patient preference.

Patterns of care for carcinoma of the prostate gland: results of a national survey of 1984 and 1990.

BACKGROUND: The annual incidence of carcinoma of the prostate gland increased from an estimated 76,000 cases in 1984 to 200,000 in 1994. Part of this increase may be the result of increased detection. Management of the disease has also changed. To measure such changes, the American College of Surgeons conducted a patient care evaluation study of carcinoma of the prostate gland. STUDY DESIGN: Information was voluntarily submitted by cancer registrars on forms designed by a team of specialists. Data were received from 730 hospitals (of 2,000 hospitals invited for the study) on 14,716 patients with newly diagnosed adenocarcinomas of the prostate gland in 1984 and from 1,035 hospitals for 23,214 patients with carcinoma of the prostate gland in 1990. RESULTS: From 1984 to 1990, there was increased diagnostic use of the prostate specific antigen (PSA) test (from 5.1 to 66.4 percent of incident carcinomas) and transrectal ultrasound (TRUS) (0.9 to 19.7 percent). Use of the prostatic acid phosphatase assay declined from 62.4 to 47 percent. Although the proportion of early stage (0, I, II) disease increased for all racial or ethnic groups combined, the greatest increase was for whites (from 57.3 to 60.6 percent), while the increase for African-Americans was less (from 46.9 to 48.3 percent). The use of radical prostatectomy without radiation therapy or chemotherapy increased from 7.3 to 20.3 percent and the proportion of patients receiving no carcinoma-directed treatment decreased from 37.8 to 30 percent. Radiation therapy remained the same. Hormone therapy without radical prostatectomy declined from 24.4 to 19.7 percent. African-Americans had a lower five-year survival rate than whites, even when stratified for stage. CONCLUSIONS: The diagnostic use of the PSA test and TRUS increased markedly by 1990 and may have contributed to the increased diagnosis of carcinomas of the prostate gland and the earlier stage at diagnosis. The overall use of radical prostatectomy has increased and the proportion of patients receiving no treatment has decreased. African-Americans had a lower five-year survival rate than other groups, even when stage was controlled.

Reported family history of cancer in 1,271 prostate cancer cases and 1,909 controls.

Prostate cancer risk has been associated with a family history of the disease. A two- to three-fold increase in risk has been observed in several studies. Details concerning modification of this risk by age, type of familial history of prostate cancer, and possible involvement of history of cancer at other sites have been less well documented. This case-control study of 1,271 prostate cancer patients and 1,909 control subjects admitted to Roswell Park Cancer Institute in Buffalo, NY, found age-adjusted increased risk associated with reporting a history of prostate cancer in a father (RR = 2.3, 95% Cl 1.4-3.3) or brother (RR = 2.5, 95% Cl 1.6-3.9). Subjects with both a father and brother affected had a 6.5-fold (95% Cl 1.4-30.5) increased risk of prostate cancer. Greater risk were observed at younger ages of diagnosis. Risks associated with reporting a father or a brother affected were not significantly elevated for patients over age 70 at diagnosis. No significant differences in patients reporting histories of cancer other than prostate cancer were observed regardless of relationship, age at diagnosis, or type of cancer examined. These observations from a large cancer patient population may be useful when making recommendations for cost-effective prostate cancer screening and for directing investigators to the potentially most informative subjects.

National survey of patterns of care for brain-tumor patients.

An excellent response by participating institutions was realized in this survey of patterns of care for patients with primary brain tumors. Since the histopathology of the tumor is such a strong predictor of outcome and influences care so greatly, most analyses were performed not only on the overall series of patients but also by World Health Organization histological classification. Several factors that influence outcome were identified: tumor type, patient age, patient Karnofsky rating, tumor location, and therapy. Very few cases were coded as regards the American Joint Committee on Cancer clinical stage, and few potentially eligible cases were placed in investigative protocols. It behooves those centers providing investigative protocol opportunities to develop liaisons with practicing physicians nearby as well as at some distance and to provide an organizational framework that will make participation in these protocols practical for a larger segment of our brain-tumor patient population. Between 1980 and 1985, the increased use of magnetic resonance imaging in neuroradiology is apparent as well as the increased use of stereotactic biopsy and interstitial radiotherapy. Complications of therapy seem acceptably low. Five-year survival for benign brain tumor is high, while that for the most common primary tumor, glioblastoma multiforme, is only 5.5%. Some of the findings in this survey confirm those from the literature while others, particularly the pattern of care, represent new data.

Pretreatment transurethral resection of prostate cancer and disease-free survival.

Data from the American College of Surgeons' national survey on prostate cancer were analyzed to determine whether recurrence-free survival differs between those patients diagnosed by transurethral resection of the prostate (TURP) and those diagnosed by needle biopsy. Only patients who received radiation therapy as treatment were included in this analysis. There were 461 patients diagnosed by TURP and 541 patients by needle biopsy. Disease free survival was calculated according to the state and tumor differentiation. Except in stage B1, none of the groups showed a statistically significant difference in recurrence-free survival between the two diagnostic procedures. The results of this analysis suggest that the disease-free survival of patients with radiation-treated prostate cancer diagnosed by TURP and needle biopsy are similar.