Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer

BACKGROUND: In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake. METHODS: In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided. RESULTS: The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03). CONCLUSIONS: Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted.     

Is low selenium status a risk factor for lung cancer?

The hypothesis that low selenium may in some circumstances be a risk factor for lung cancer was investigated in a case-control study nested within a longitudinal study. Serum samples from 9,101 cancer-free individuals were collected and stored at -20 degrees C by the Finnish Mobile Clinic in 1968-1971 and 1973-1976. During follow-up until the end of 1991, 95 cases of lung cancer were diagnosed. Selenium concentrations were determined from the serum samples of the cases and 190 controls, individually matched for sex, age, and place of residence. Mean levels of serum selenium in cases and controls were 53.2 microg/liter and 57.8 microg/liter, respectively. The relative risk of lung cancer between the highest and lowest tertiles of serum selenium, adjusted for smoking, serum alpha-tocopherol, serum cholesterol, serum copper, serum orosomucoid, and body mass index (kg/m2), was 0.41 (95% confidence interval (CI) 0.17-0.94). The association was stronger at lower levels (<5.9 mg/liter) of alpha-tocopherol (relative risk=0.24, 95% CI 0.07-0.85). The association was also pronounced among current smokers and at higher levels of serum orosomucoid and serum copper. The relative risk for smokers who were twice ranked in higher selenium tertiles, at an interval of 4-7 years, in comparison with smokers who remained in the lowest tertile was 0.16 (95% CI 0.04-0.74). In accordance with the hypothesis, the findings suggest that very low selenium status may contribute to the risk of lung cancer.     

Serum fatty acids and the risk of fatal cancer. MRFIT Research Group. Multiple Risk Factor Intervention Trial

To examine the relation between serum fatty acids and cancer, the authors conducted a nested case-control study of 108 middle-aged men who died of cancer and 215 men without cancer, who were enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) between 1973 and 1976. Control subjects were matched to case subjects on age, smoking status, treatment assignment, date of randomization, and clinical center. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and analyzed their association with cancer. In stepwise logistic regression analyses that controlled for the MRFIT selection criteria variables and for alcohol consumption, no fatty acid was significantly associated with overall risk of cancer death (all p > 0.05). Serum levels of phospholipid dihomogammalinolenic acid (20:3), an essential fatty acid, were inversely associated with the risk of dying from lung cancer; a standard deviation increase was associated with a 32% decrease in risk (p = 0.05). Dietary cholesterol intake was associated with the risk of nonlung, non-digestive tract cancers; a standard deviation increase (331 mg/day) was associated with a 75% increase in risk (p = 0.02). The authors found no evidence to suggest that increased dietary intake or serum levels of polyunsaturated fatty acids were associated with an increased risk of fatal cancer among middle-aged men at high risk for coronary heart disease. The clinical significance of the inverse association between dihomogammalinolenic acid and lung cancer death is uncertain and requires confirmation.     

Lessons from basic research in selenium and cancer prevention

The article reviews the progress in basic research of selenium and cancer prevention during the past decade. Special emphasis is placed on the following four major areas of discussion: 1) chemical forms of selenium and anticarcinogenic activity; 2) selenium-enriched food; 3) in vitro effects of selenite vs. monomethylated selenium; and 4) aromatic selenium compounds. It is clear that basic research has contributed new knowledge to our understanding of selenium biochemistry, anticancer efficacy and regulation of cell growth. Some of this information could be ready for incorporation into the design of a second-generation selenium trial in humans.     

High risk of HIV-related mortality is associated with selenium deficiency

The management of mild to severe croup has undergone dramatic changes in the last 5 years, primarily due to the increased understanding of the benefits of treating it with steroids. Steroids have been used in the treatment of croup for many years, but, until recently, their use has remained controversial. Earlier studies were often not blinded or used inappropriate outcome measures, such as respiratory rate, which have not proven appropriate. Two attempts to review the literature in 1980 and 1989 cautiously supported the use of steroids. Despite these recommendations many practitioners continued to view croup in most cases as a benign self-limited condition, and since steroids have potential side-effects, their use was not considered justified. More recently, however, a number of developments such as the successful use of the inhaled steroid budesonide and oral dexamethasone have reinforced the argument for using steroids. Recent work has also shown that both inhaled and systemic steroids work by 1 hour and dramatically reduce morbidity and hospitalization time. The demonstration that an oral dose of 0.15 mg/kg dexamethasone is as effective as larger doses has made the use of systemic steroids more acceptable to many practitioners. All children with croup severe enough to be admitted to hospital should receive steroids. Two recent studies have shown that steroids also benefitted children who presented to emergency departments for treatment, but whose croup was not considered severe enough for admission. The type of steroid, the dose, and the mode of administration will need to be decided by the attending clinician.     

Physical activity and the risk of breast cancer

BACKGROUND: Because physical activity may affect hormonal concentrations and energy balance, we decided to investigate whether everyday exercise is related to the risk of breast cancer. METHODS: During 1974 to 1978 and 1977 to 1983, a total of 25,624 women, 20 to 54 years of age at entry, enrolled in health surveys and answered questionnaires about leisure-time and work activity. RESULTS: During a median follow-up of 13.7 years, we identified 351 cases of invasive breast cancer among the 25,624 women in the cohort. Greater leisure-time activity was associated with a reduced risk of breast cancer, after adjustments for age, body-mass index (the weight in kilograms divided by the square of the height in meters), height, parity, and county of residence (relative risk, 0.63; 95 percent confidence interval, 0.42 to 0.95), among women who exercised regularly, as compared with sedentary women (P for trend=0.04). In regularly exercising women, the reduction in risk was greater in premenopausal women than in postmenopausal women, and greater in younger women (<45 years at study entry) than in older women (> or =45 years) (relative risk, 0.38; 95 percent confidence interval, 0.19 to 0.79). In stratified analyses the risk of breast cancer was lowest in lean women (body-mass index, <22.8) who exercised at least four hours per week (relative risk, 0.28; 95 percent confidence interval, 0.11 to 0.70). The risk was also reduced with higher levels of activity at work, and again there was a more pronounced effect among premenopausal than postmenopausal women. CONCLUSIONS: Physical activity during leisure time and at work is associated with a reduced risk of breast cancer.     

Dietary factors and the risk of endometrial cancer

BACKGROUND: Endometrial cancer is associated with overweight, but little is known on its possible relationship with specific aspects of diet. METHODS: The relationship between dietary factors and the risk of endometrial cancer was investigated in a case-control study conducted in Switzerland and Northern Italy on 274 patients with histologically confirmed endometrial cancers and 572 control subjects admitted to the hospital for acute nongynecologic disorders that were not hormone related, metabolic, or neoplastic. RESULTS: Significant direct associations were observed with (1) the total energy intake (odds ratio [OR] for the highest versus the lowest consumption tertile = 2.7) and, after allowance for energy intake, (2) the frequency of consumption of most types of meats, eggs, beans or peas, added fats (OR for total added fat = 2.5), and sugar (OR = 2.5). Significant protection, of the order of 40-60% reduction in the highest versus the lowest consumption tertile, was conferred by elevated intake of most vegetables and fresh fruit and whole grain bread and pasta. This was reflected in the low OR for the highest tertiles of intake of beta-carotene and ascorbic acid (OR for the highest versus the lowest consumption tertile after allowance for energy intake = 0.5). CONCLUSIONS: The current study suggests that, aside from the predictable adverse effects of overeating and consequent overweight, some qualitative aspects of the habitual diet may also be associated with the risk of endometrial cancer, chiefly, the intake of animal proteins and fat (directly) and of fresh fruit, vegetables, and fibers (inversely).     

Iron intake and the risk of colorectal cancer

Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period. Subsite analysis showed that the risk of colon cancer due to iron intake was elevated throughout the colon for both men and women, with the highest adjusted risks for the interquartile range seen in the proximal colon for females (relative risk, 1.51; 95% confidence interval, 1.41-1.60). The risk of rectal cancer was not significantly elevated for men or women. Elevated serum iron was also associated with increased risk; however, this effect was strongest in the distal (rather than proximal) colon and was significant only among females (adjusted relative risk, 1.73; 95% confidence interval, 1.03-2.92). The mean transferrin saturation was higher among cases than controls (30.7 versus 28.7%), but total iron-binding capacity did not seem to predict the occurrence of colorectal cancer. Proportional hazards models confirmed that the effects of iron and serum iron were not confounded by age, gender, energy consumption, fat intake, or other known risk factors for colorectal cancer. These data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. These differences may be due to such factors as oxidation state, binding proteins and the presence of other cofactors such as bile acids, products of bacterial metabolism.     

Passive smoking and risk of cancer

During the last two decades there have been frequent discussions as to whether passive smoking causes cancer, or not. It is difficult to carry out satisfactory studies on this issue, partially because any increased risk of cancer seems modest. The tobacco industry has not only attempted to make the public aware of studies which conclude that passive smoking is harmless, but it has also tried to keep alive the discussion as to whether exposure to passive smoking is harmful, or not. A large number of studies has been carried out on the possible impact passive smoking may have on the risk of lung cancer, and it seems justifiable to conclude that passive smoking does increase the risk of this type of cancer. For other types of cancer too few studies have been performed to draw any firm conclusions.     

Catechol-O-methyltransferase and breast cancer risk

Recent studies suggest that a polymorphism in catechol-O-methyltransferase (COMT) is associated with increased risk of breast cancer. Methylation by COMT is the principal pathway for inactivation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis. We examined the association of COMT genotype and breast cancer risk in a population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 654 cases and 642 controls, with approximately equal numbers of African-American and white women and women under the age of 50 and aged 50 or over. Contrary to previous reports, we did not observe an association between one or more copies of the low activity COMT allele (COMT-L) and breast cancer risk. Multivariate relative risks (RRs) were 0.8 (95% confidence interval: 0.6-1.1) for COMT-HL and 0.8 (0.6-1.1) for COMT-LL, compared with the COMT-HH genotype. RRs for COMT did not differ among African-American and white women and we did not observe strong modification of RR estimates by menopausal status, body mass index, physical activity or other covariates. Our results suggest that COMT genotype is not related to breast cancer risk.     

Occupation and the risk of lung cancer in Uruguay

OBJECTIVES: The purpose of this study was to provide more information regarding the risk of lung cancer associated with asbestos, and other exposures in the Uruguayan work force. METHODS: This multisite case-referent study was part of a large project designed for evaluating the role of occupational exposures in cancer risk in Uruguay. According to the design employed, cases were a subset of the data base corresponding to a particular site (in this instance lung cancer), and they were compared with all other sites combined (referents). RESULTS: Significant increases in risk associated with workers in the construction industry were mainly observed for squamous-cell carcinoma. Asbestos, silica dust, and DDT (dichlorodiphenyltrichloroethane) exposure were also associated with increases in the risk of lung cancer. Pipefitters, bakers, and textile workers were also at increased risk of developing lung cancer. CONCLUSIONS: Workers employed in the construction industry, as well as those exposed to DDT may have an excess risk of lung cancer. These findings are particularly important in showing that developing countries like Uruguay display risk patterns of similar magnitude as those observed in developed communities.     

Well-done meat intake and the risk of breast cancer

BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.     

Rheumatoid arthritis and risk of cancer

In the current study we linked data from the Danish Hospital Discharge Register and the Danish Cancer Registry to estimate cancer occurrence among more than 20,000 patients hospitalized at least once with rheumatoid arthritis during 1977-1987. During a follow-up interval of up to 15 years, we found increased risks of non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer, while the risk of colorectal cancer was decreased. These findings were all in agreement with the results of previous studies from two other Nordic countries, which were based on a similar type of data. We also found an excess of non-melanoma skin cancer and a deficit of female breast cancer, of which only the breast cancer observation had been seen in an earlier study.     

A woman's build and the risk of breast cancer

A woman's build and the risk of breast cancer seem to be related. While relative overweight, as described by the body mass index, seems to be associated with increased breast cancer risk in postmenopausal women, overweight in premenopausal women seems slightly protective. Papers from a MEDLINE search are reviewed regarding the association between build and the development of breast cancer. Different aspects of build, such as height, weight, body mass index and body shape, are discussed. The more prominent associations found through this search are a positive association between height and breast cancer risk both in pre- and postmenopausal women. Regarding body mass index, the association is negative in premenopausal women and positive in postmenopausal women. Body shape described as masculine versus feminine seems to have no impact on breast cancer risk in premenopausal women, but seems to be positively associated with breast cancer in postmenopausal women. Possible biological mechanisms responsible for the associations with breast cancer risk are discussed, including endogenous oestrogens, androgens and glucose metabolic substances. Avoiding or reducing postmenopausal overweight may modify breast cancer risk indicators in a more favourable direction.     

Evaluating the genetic risk of breast cancer

Progress genetics has endless implication for primary care and for people at risk for hereditary breast cancer. Nurse practitioners will be increasingly challenged to order and interpret genetic tests, provide genetic counseling, and assume responsibility for protecting patient privacy. Yet primary care practitioners may not be completely prepared to provide the necessary background information. This article provides guidelines for evaluating family history risk for inherited breast cancer risk. Also discussed are implications for presymptomatic testing of the BRCA1 and BRCA2 genes for adult-onset breast and ovarian cancer.