Nachimuthu Natarajan

Beta‐carotene and animal fats and their relationship to prostate cancer risk. A case—control study

A case—control study of 371 prostate cancer patients and comparable control subjects admitted to Roswell Park Memorial Institute (RPMI), Buffalo, New York, was conducted. Data were obtained from routine epidemiologic questionnaires administered to all patients on admission. An index of beta‐carotene intake was computed based on the vitamin A activity of 27 fruits and vegetables included in a food frequency checklist. A similar measure of fat intake from meats was computed based on nine meats included in the checklist. Intake frequencies of common and alcoholic beverages also were studied. A significant age‐adjusted and residence‐adjusted protective effect for high levels of beta‐carotene intake was observed (relative risk [RR], 0.60; 95% confidence interval [CI], 0.37 to 0.99). This effect was evident particularly among men 68 years of age and younger (RR, 0.30; 95% CI, 0.13 to 0.66), but not among subjects older than 68 years of age. A trend toward increased risk for fat intake was not significant. However, the reported usual consumption of high‐fat milk was associated with increased risk (RR, 1.92; 95% CI, 1.05 to 3.50). A greater reported frequency of whole milk intake was similarly associated with increased risk. Men who reported drinking three or more glasses of whole milk daily had an RR of 2.49 (95% CI, 1.27 to 4.87), compared with men who reported never drinking whole milk. When these findings are evaluated in the context of other recent studies, the weight of the evidence appears to favor the hypothesis that animal fat intake is related to increased risk of prostate cancer.

Race‐related differences in breast cancer patients results of the 1982 national survey of breast cancer by the american college of surgeons

Data from the 1982 breast cancer survey of the American College of Surgeons were used to evaluate factors related to clinical, epidemiologic, and survival differences between black and white patients. Breast cancer in blacks was not discovered as early as in whites. Distribution of pathologic types of tumors were similar for both races with the exception of medullary carcinoma, which was more frequent in blacks than in whites. Estrogen receptor‐positive tumors were found significantly less frequently in blacks compared with whites. Survival was better for whites compared with blacks within each axillary nodes group 0, 1 to 3, and 4+. Black women with negative or positive estrogen receptors had lower survival rates than white women of the same receptor status. A regression analysis using Coxs proportional hazards model showed race, clinical stage or axillary nodal status, age at diagnosis, and estrogen receptor status as significant predictors of survival. Significant differences between black and white patients were also observed with respect to the report of family history of breast cancer, age at first pregnancy, number of pregnancies, and age at cessation of menses. Cancer 56: 1704‐1709, 1985.

The Nutritional Prevention of Cancer: 400 Mcg Per Day Selenium Treatment

Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.

MCM2 Is an Independent Predictor of Survival in Patients With Non–Small-Cell Lung Cancer

PURPOSE Minichromosome maintenance protein 2 (MCM2) is a component of the prereplicative complex. It is essential for eukaryotic DNA replication and is only expressed in proliferating cells. The prognostic utility of MCM2 compared with Ki-67, another marker of proliferating cells, on survival of patients with non-small-cell lung cancer (NSCLC) was studied. PATIENTS AND METHODS We examined the immunohistochemical expression of MCM2 and Ki-67 in primary pathologic tumor specimens from 221 NSCLC patients. For each marker, the fraction of tumor cells with positive staining was assessed as a percentage and categorized into four groups: 0% to 24%, 25% to 49%, 50% to 74%, and > or = 75%. MCM2 and Ki-67 immunoreactivities were compared with each other, and associations with pathologic and clinical parameters predictive of survival were analyzed with the chi(2) test. Cox regression models were used to assess associations between MCM2 and Ki-67 and survival while controlling for confounders. RESULTS Independent variables significantly associated with survival were tumor stage, performance status, and staining category. Patients with less than 25% MCM2 immunoreactivity had a longer median survival time than patients with > or = 25% MCM2 immunoreactivity (46 v 31 months; P =.039) and a lower relative risk (RR) of death (RR, 0.55, 95% confidence interval, 0.34 to 0.88). There was no significant association between survival and Ki-67 expression. CONCLUSION Immunostaining of tumor cells for MCM2 is an independent prognostic parameter of survival for patients with NSCLC. Interpretable results can be obtained on more than 96% of paraffin-embedded specimens, and approximately 35% will be in the favorable subgroup, with less than 25% positively stained tumor cells. Whether MCM2 is predictive of response to therapy needs to be studied.

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.

Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment

Background: This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high-risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre-malignant central airway lesions. Methods: 402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) ⩾20 pack year history of tobacco use, (2) asbestos-related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV1) <70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for >2 years. All eligible patients underwent AFB, a low-dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT-detected pulmonary nodules and surveillance-detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures. Results: Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre-malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma-in-situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre-malignant changes on AFB (p<0.001). Conclusion: Bimodality surveillance will detect central lung cancer and pre-malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high-risk patients, regardless of sputum cytology findings.

Patterns of milk consumption and risk of cancer

The reported milk consumption habits of 3,334 cancer patients and 1,300 comparable control subjects seen at Roswell Park Memorial Institute were studied. The cancer patient group included persons diagnosed with cancers of the oral cavity, stomach, colon, rectum, lung, breast, uterus, cervix, prostate, or bladder. Data were obtained by means of a standardized admissions questionnaire. As a group, control patients were more likely to report never drinking whole milk; cancer patients more often reported frequent consumption of whole milk. Relative risks of different patterns of milk consumption for specific cancer diagnoses, adjusted for sex, age, smoking history, education, and county of residence, were calculated with multiple logistic regression analysis. Elevated risks for frequent consumption of whole milk relative to not drinking milk were observed for cancers of the oral cavity, stomach, colon, rectum, lung, bladder, breast, and cervix. Reduced risks for frequent consumption of 2% milk relative to not drinking milk were observed for cancers of the oral cavity, stomach, rectum, lung, and cervix. Preference for exclusive consumption of reduced-fat milk was linked to significant risk reduction for oral and cervical cancers, and drinking only whole milk was linked to significant risk increases for cancers of the oral cavity, stomach, rectum, lung, and breast. Some associations were observed for a computed index of milk fat intake, but the overall pattern of effects was not fully explained by variations in fat content. The effects observed for some sites may be confounded by other dietary or nondietary correlates of risk.

Carcinoma of prostate in men less than fifty years old Data from American College of Surgeons' national survey☆

Abstract The data of the long-term survey on prostate cancer of the Commission on Cancer of the American College of Surgeons were analyzed to assess differences in stage of disease, diagnostic and therapeutic procedures, and survival in men with prostate cancer less than fifty years of age compared with older men. Of 20,156 patients, 168, 0.8 per cent of the survey group, were less than fifty years old. There was significantly greater incidence of metastatic disease in the younger age group, with a concomitant deficit in Stage A or occult prostate cancer in those less than fifty years old. Diagnosis was made most frequently by needle biopsy of the prostate in younger patients, while the older patients underwent transurethral resection of the prostate as a diagnostic procedure in the majority of cases. There was a more frequent use of radical prostatectomy and radiation therapy for all stages of disease in the less than fifty-year-old group, while transurethral resection of the prostate alone or hormone therapy alone was the predominant therapeutic modality in those fifty and older. Comparison of survival by stage of disease showed significantly better survival for younger patients with Stage B disease at five years (84% vs 68%) and at ten years (70% vs 48%). Survival was slightly better in younger patients at five years for other stages of disease. Although prostate cancer is more likely to be metastatic at the time of diagnosis in men less than fifty, there does not appear to be any significant biologic differences in prostate cancer in men less than fifty years old when compared with older men.

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.

Hormone Replacement Therapy as a Risk Factor for Non-Small Cell Lung Cancer : Results of a Case-Control Study

Purpose: It was the aim of this study to assess the risk of lung cancer in postmenopausal women who received hormone replacement therapy (HRT). Experimental Design: This case-control study involves women who received medical services at Roswell Park Cancer Institute (RPCI) in Buffalo, New York, between 1982 and 1998, and who agreed to complete an epidemiological questionnaire. Participants with missing smoking data were excluded. The case group consisted of 595 women with primary lung cancer. Controls included 1,195 women, randomly selected from a pool of 5,845 eligible individuals, who received medical services at RPCI for non-neoplastic conditions; they had come to RPCI with a suspicion of neoplastic disease, but were diagnosed with neither benign nor malignant conditions. Controls were frequency matched 2:1 to cases on 5-year age intervals and exposure to smoking (ever/never). Cases and controls were comparable for age (means 61.3 and 61.0 years) and ever smoking (90%). Results: There were more former smokers among the cases (67 vs. 59% in controls); cases were less likely to be high school educated, were thinner, and were less likely to report HRT use compared with controls. Overall, hormone use was associated with a significant reduction in risk of lung cancer (adjusted odds ratio = 0.67; 95% confidence interval 0.53–0.85). Stratified analyses showed significant reductions in lung cancer risk in former smokers and women with normal to low body mass index. Conclusion: This study supports the hypotheses that there is a protective effect of HRT use on lung cancer risk in women.