Consumption of non-alcoholic beverages and prostate cancer risk.

Our objective was to investigate the relations between the consumption of coffee, tea and carbonated beverages and the development of prostate cancer. The design was a population-based case-control study set in Montreal. The analysis was restricted to the subset of men, aged 45-70 years, who underwent interviews in which aspects of lifelong consumption of non-alcoholic beverages were ascertained. There were 399 incident cases of prostate cancer, 476 population controls and 621 cancer controls. There was no association between the consumption of either coffee or carbonated beverages and the development of prostate cancer. Among daily tea drinkers, the odds ratio associated with the highest tertile of cumulative consumption was 2.0 (95% confidence interval (CI) 1.3-3.0) when using population controls and 1.6 (95% CI 1.0-2.4) when using cancer controls. In conclusion, the consumption of coffee or carbonated beverages does not influence the risk of prostate cancer. Our findings provide no support to the hypothesis that tea consumption may be protective. While tea consumption may increase prostate cancer risk, we were unable to rule out alternative explanations for the positive association that we observed.

The effects of tricyclic antidepressants on breast cancer risk.

To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case-control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged 35 years from 1981-995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23,517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11-15 years later (2.02, 95% confidence interval: 1.34-3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use.

Case-control study of alcohol consumption and prostate cancer risk in Montréal, Canada.

OBJECTIVES: to estimate the risk of prostate cancer associated with alcohol consumption. METHODS: Between 1979 and 1985 a population-based case-control study was carried out in Montréal, which accrued over 4000 men in total, including cases of prostate cancer, other cancers, and population controls. The present analysis was restricted to the subset, aged 45-70 years. who underwent face-to-face interviews, in which aspects of lifelong alcohol consumption were ascertained. The cancer control series was further restricted to men whose tumor types were considered unrelated to alcohol consumption. There were 399 incident cases of prostate cancer, 476 population controls, and 674 cancer controls. RESULTS: When using the population controls, risk increased with increasing cumulative consumption of alcohol. There was no decrease in risk after quitting. Risk was particularly high among those who reported having started before age 15 years (odds ratio = 3.8; 95% confidence interval: 1.6-9.3). The results obtained using the cancer controls were less pronounced, but still indicated an excess risk associated with alcohol consumption. Beer was the most prevalent type of alcohol consumed in this population and showed the strongest association with prostate cancer. CONCLUSIONS: The results are consistent with an increase in the risk of prostate cancer due to alcohol consumption.

Joint effects of smoking and body mass index on prostate cancer risk.

Between 1979 and 1985, a population-based case-control study of cancer at multiple sites was carried out in Montréal. A total of 399 cases with histologically confirmed prostate cancer and 476 population controls, 45-70 years of age, gave face-to-face interviews and provided adequate smoking histories. We analyzed the effects of smoking cigarettes only and of smoking cigars, or pipes, or both, with or without cigarettes, on the risk of prostate cancer. Overall, the associations between smoking cigarettes and prostate cancer were weak and compatible with no effect; the associations with cigar and pipe smoking were stronger. Among men with high body mass index, however, we found appreciable associations between cigarette smoking and prostate cancer risk. A history of ever smoking daily was associated with an odds ratio of 2.31 (95% confidence interval = 1.09-4.89). Risk increased with the amount smoked per day and with the duration of smoking. Taken together, the findings of increased risk associated with cigar and pipe smoking and the findings of increased risk associated with cigarette smoking among obese men suggest that tobacco smoking may be a risk factor for prostate cancer.

Activities and exposures during leisure and prostate cancer risk.

The objective of this study was to identify activities and exposures during leisure that might be associated with the development of prostate cancer. We analyzed data derived from a population-based case-control study that was carried out in Montreal between 1979 and 1985. Men (>4000) were interviewed, including cases of prostate cancer, other cancers, and population controls. The present analysis was restricted to the subset, aged 45-70 years, who underwent face-to-face interviews in which aspects of activities and exposures during leisure were ascertained. There were 400 incident cases of prostate cancer and 476 population controls. We calculated odds ratios (OR) for prostate cancer, adjusted for age, ethnic origin, respondent status, family income, body mass index, cigarette smoking, and alcohol consumption. Home or furniture maintenance was associated with an increased risk [OR, 1.4; 95% confidence interval (CI), 1.0-1.9], as was painting, stripping, or varnishing furniture (OR, 2.1; 95% CI, 0.7-6.7). Exposure during leisure to metal dust was associated with prostate cancer (OR, 3.2; 95% CI, 1.0-9.9), as was exposure to lubricating oils or greases (OR, 2.2; 95% CI, 1.2-3.7) and exposure to pesticides or garden sprays (OR, 2.3; 95% CI, 1.3-4.2). These findings are consistent with results derived from studies of occupational exposures.

Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage.

We carried out a nested case-control study to measure the rate ratio (RR) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug (NSAID) use. The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970. Four controls/case, matched on age and sampling time, were randomly selected. Dispensing rates during successive time periods characterized NSAID exposure. RRs associated with exposure during each period were adjusted for exposure during the others. Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing samples of subjects accrued from mid-1991 to mid-1995. We accrued 5882 cases and 23,517 controls. Increasing NSAID exposure 2-5 years preceding diagnosis was associated with a trend towards a decreasing RR (P-trend = 0.003); for the highest exposure level RR = 0.76, 95% confidence interval 0.63-0.92. This protective effect could not be attributed to confounding by other determinants. In analyses involving only the cases, NSAID exposure 2-5 and 6-10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour (> 5 cm diameter) or distant metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis.

The influence of parental age on the risk of Wilms' tumour.

The Brazilian Wilms' Tumour Study Group carried out a hospital-based multicentre case-control study of potential risk factors for the disease between April 1987 and January 1989. The parents of 109 cases of Wilms' tumour (WT) were interviewed when they were admitted to hospital for diagnosis and treatment. Also interviewed were the parents of two controls per case, matched for age, sex and interviewer, who were admitted to the same or nearby hospitals for treatment of non-neoplastic conditions. Odds ratios adjusted for family income and parental education were calculated by conditional logistic regression. Among cases diagnosed before 25 months of age there was a marked gradient of increasing risk of WT with increasing maternal age at the time of the child's birth. There was no increased risk for cases diagnosed after 25 months of age. The effects of paternal age were less marked. Possible explanations for these results are discussed.

The influence of parental age on the risk of Wilms tumour

The Brazilian Wilms' Tumour Study Group carried out a hospital-based multicentre case-control study of potential risk factors for the disease between April 1987 and January 1989. The parents of 109 cases of Wilms' tumour (WT) were interviewed when they were admitted to hospital for diagnosis and treatment. Also interviewed were the parents of two controls per case, matched for age, sex and interviewer, who were admitted to the same or nearby hospitals for treatment of non-neoplastic conditions. Odds ratios adjusted for family income and parental education were calculated by conditional logistic regression. Among cases diagnosed before 25 months of age there was a marked gradient of increasing risk of WT with increasing maternal age at the time of the child's birth. There was no increased risk for cases diagnosed after 25 months of age. The effects of paternal age were less marked. Possible explanations for these results are discussed.

The expression of XIF3 in undifferentiated anterior neuroectoderm, but not in primary neurons, is induced by the neuralizing agent noggin.

The gene XIF3 encodes a neural-specific type-III intermediate filament protein whose expression in the embryo precedes that of the neurofilaments by several hours. We now show, by in situ hybridization, that it is expressed at the neurula stage in primary neurons and, to a lesser extent, in undifferentiated anterior neuroectoderm. At the swimming tadpole stage, strong expression is restricted to the midbrain-hindbrain boundary, even-numbered rhombomeres of the hindbrain and the Vth and VIIth cranial ganglia. XIF3 gene expression can be induced in ectodermal cells (animal caps) derived from blastula when grown to the neurula stage in the presence of the neuralizing agent noggin. In agreement with the proposed ability of noggin to neuralize, but not to promote neuronal differentiation, we find that the pattern of noggin-inducible XIF3 expression in animal caps is consistent with expression in undifferentiated anterior neuroectoderm but not in primary neurons.

A developmental hypothesis to explain the multicentricity of breast cancer.

In this article the author proposes that the multicentricity of breast cancer might be explained by a developmental hypothesis. Genetic alterations ("hits") occurring in epithelial stem cells during the development of the breast may be transmitted to populations of daughter cells during growth. As a result, areas of the breast may be predisposed to malignant transformation with the occurrence of further genetic hits. Areas with the same predisposition should be anatomically connected, and earlier hits during breast development should result in larger areas of predisposition. The multicentricity of breast cancer would be explained if multiple lesions--monoclonal for the predisposing genetic hit and polyclonal for subsequent hits--developed within a predisposed area. Multiple lesions arising from the spread of disease by extension would be expected to share many genetic hits. The author discusses the implications that further evidence supporting the developmental hypothesis would have for the prevention and treatment of breast cancer.

Retinoid receptors promote primary neurogenesis in Xenopus.

Retinoid receptors, which are members of the nuclear hormone receptor superfamily, act as ligand-dependent transcription factors. They mediate the effects of retinoic acid primarily as heterodimers of retinoic acid receptors (RARs) and retinoid X receptors (RXRs). To analyse their function, xRXR beta synthetic mRNA was injected into Xenopus embryos in combination with normal and mutated xRAR alpha transcripts. Two informative phenotypes are reported here. Firstly, over-expression of xRXR beta with xRAR alpha results in the formation of ectopic primary neurons. Secondly, blocking retinoid signalling with a mutated xRAR alpha results in a lack of primary neurons. These two phenotypes, from contra-acting manipulations, indicate a role for retinoid signalling during neurogenesis.

Use of dipyrone during pregnancy and risk of Wilms' tumor. Brazilian Wilms' Tumor Study Group.

We evaluated the risk of Wilms' tumor in the offspring of women taking various medications during pregnancy in a case, control study conducted in Brazil. The study accrued 109 cases and 218 age- and gender-matched hospital controls. After adjustment for known confounders, we found a strong association with ingestion of dipyrone (odds ratio = 10.9; 95% confidence interval = 2.4-50) particularly in women from low-income families. Although dipyrone-containing analgesics are banned in Europe and North America, they are widely prescribed in Brazil and are given as free samples in neighborhood clinics providing free health care. The strong effect specific to low-income women may result from higher individual consumption compared with women at higher income levels.

Use of dipyrone during pregnancy and risk of Wilms tumor

We evaluated the risk of Wilms' tumor in the offspring of women taking various medications during pregnancy in a case, control study conducted in Brazil. The study accrued 109 cases and 218 age- and gender-matched hospital controls. After adjustment for known confounders, we found a strong association with ingestion of dipyrone (odds ratio = 10.9; 95% confidence interval = 2.4-50) particularly in women from low-income families. Although dipyrone-containing analgesics are banned in Europe and North America, they are widely prescribed in Brazil and are given as free samples in neighborhood clinics providing free health care. The strong effect specific to low-income women may result from higher individual consumption compared with women at higher income levels.

A Xenopus c-kit-related receptor tyrosine kinase expressed in migrating stem cells of the lateral line system.

The mammalian c-kit receptor tyrosine kinase gene is required during embryogenesis for the survival and/or proliferation of three migrating stem cell populations: primordial germ cells, haematopoietic stem cells and neural crest-derived melanoblasts. We have cloned a Xenopus gene, XKrk1, whose closest relative is c-kit. Differences in the expression pattern suggest that XKrk1 is not the Xenopus homologue of c-kit; however, it is expressed in a migrating stem cell population, the precursor cells for the mechanosensory lateral line system. XKrk1 is the first reported marker for lateral line stem cells.

Parental exposures to pesticides and risk of Wilms' tumor in Brazil.

Wilms' tumor is one of the most common abdominal childhood malignancies. Wilms' tumor rates in Brazil are among the highest in the world. This prompted the Brazilian Wilms' Tumor Study Group to conduct a hospital-based, multicenter, case-control investigation of environmental risk factors for the disease. Between April 1987 and January 1989, the authors collected information on relevant occupational exposures by interviewing the parents of 109 Wilms' tumor cases admitted to hospitals in Sao Paulo, Salvador, Belo Horizonte, and Jau. Also interviewed were the parents of 218 age- and sex-matched control children who had been admitted for treatment of nonneoplastic diseases to the same or nearby hospitals. Odds ratios (ORs) adjusted for income and education were calculated by conditional logistic regression. Consistently elevated risks were seen for farm work involving frequent use of pesticides by both the father (OR = 3.24, 95% confidence interval (CI) 1.2-9.0) and the mother (OR = 128.6, 95% CI 6.4-2,569). These risk elevations were restricted to cases diagnosed after 2 years of age (ORs > 4), for paternal exposure, and after 4 years of age (OR = 14.8, 95% CI 2.2-98.8), for maternal exposure. Risk elevations were also more pronounced among boys (paternal exposure OR = 8.56, 95% CI 2.1-35.1; maternal exposure OR = 4.60, 95% CI 0.8-26.4) than among girls (paternal exposure OR = 1.31, 95% CI 0.4-4.1; maternal exposure OR = 2.03, 95% CI 0.5-8.9).

Etiology of Wilms' tumor.

Present knowledge of the pathogenesis of Wilms' tumor can be used to plan further epidemiologic investigations in a logical manner. Table 3 summarizes the epidemiologic evidence presently available that implicates various exposures. The proportion of cases of Wilms' tumor that arise from germline mutations is unknown. Future case-control studies could contribute to providing such information by systematically collecting and preserving constitutional genetic material from cases and their parents and neoplastic genetic material from their tumors. The studies that have demonstrated germline mutations so far have involved small numbers of subjects, being the equivalent of "case reports" (36, 37, 45-47, 50, 53). The techniques of molecular biology will be necessary to distinguish germline mutations or equivalent events that have been transmitted by parents from those that have arisen de novo. (Since it has already been shown that phenotypically unaffected parents can transmit relevant mutations to offspring who become affected (45, 46), the presence or absence of phenotypic abnormalities in the parents cannot be used to infer whether germinal mutations have arisen de novo.) Such studies will be laborious and expensive. The best strategy to minimize cost and labor would be restriction on age; the cases diagnosed relatively early in life (before the age of 2-3 years) are more likely to have arisen from germline mutations than those diagnosed later (34). The existence of de novo germline mutations relevant to the development of Wilms' tumor should prompt epidemiologists to search for causal exposures before conception. Preliminary evidence suggests that males have a higher germinal mutation rate (48). On the basis of the epidemiologic evidence to date, Olshan et al. have suggested the following: "paternal preconceptional exposures may play a more important role in the etiology of Wilm's tumor than maternal factors"(8,p.943). Pathologic and molecular biologic studies have shown that Wilm's tumor arises from nephrogenic rests that represent renal stem cells, the development of which has been arrested before normal differentiation occurs (2,44). Exposures that occur during intrauterine life are likely to be relevant to this process; these can be studied with epidemiologic methods, and clues have emerged (7,86,89). It is important to realize, however, that the fetus may be exposed in utero to substances to which the mother was exposed prior to conception, if these substances are excreted slowly or not at all, such as the persistent organochlorine pesticides (96,98). Study of the determinants of the growth behavior of nephrogenic rests (persistence, regression, generalized growth, or malignant transformation (2)) may be possible only in an animal model of Wilm's tumor, if one can be found in which nephroblastoma arises from nephrogenic rests. Ethylnitrosurea, an alkylating agent, causes renal tumors identical to Wilm's tumor in the opossum when given early in postnatal life (103) and in the rabbit when given transplacentally (104). Nephroblastoma in animals is one of the very few types of tumors that is inducible by chemicals via the transplacental route. This mode of induction should be regarded as as an etiologic possibility in humans as well as animals (105). As Hard, however, has pointed out, "nodular renal blastema [now known as nephrogenic rests] or nephroblastomatosis...have [sic] never been described in conjunction with nephroblastoma of animals" (105,p.184). the renal stem cells that give rise to Wilm's tumor normally disappear 4-6weeks prior to birth (19). If they persist after birth, as nephrogenic rests or otherwise, postnatal exposures could contribute to the development of Wilm's tumor. Cases diagnosed later, especially those presenting with lower stage disease, are more likely to have arisen from mutations occurring after birth. Potential carcinogens in children's diet and the home environment are worthy of close study.

Parental exposures to pesticides and risk of Wilms tumor in Brazil

Wilms' tumor is one of the most common abdominal childhood malignancies. Wilms' tumor rates in Brazil are among the highest in the world. This prompted the Brazilian Wilms' Tumor Study Group to conduct a hospital-based, multicenter, case-control investigation of environmental risk factors for the disease. Between April 1987 and January 1989, the authors collected information on relevant occupational exposures by interviewing the parents of 109 Wilms' tumor cases admitted to hospitals in Sao Paulo, Salvador, Belo Horizonte, and Jau. Also interviewed were the parents of 218 age- and sex-matched control children who had been admitted for treatment of nonneoplastic diseases to the same or nearby hospitals. Odds ratios (ORs) adjusted for income and education were calculated by conditional logistic regression. Consistently elevated risks were seen for farm work involving frequent use of pesticides by both the father (OR = 3.24, 95% confidence interval (CI) 1.2-9.0) and the mother (OR = 128.6, 95% CI 6.4-2,569). These risk elevations were restricted to cases diagnosed after 2 years of age (ORs > 4), for paternal exposure, and after 4 years of age (OR = 14.8, 95% CI 2.2-98.8), for maternal exposure. Risk elevations were also more pronounced among boys (paternal exposure OR = 8.56, 95% CI 2.1-35.1; maternal exposure OR = 4.60, 95% CI 0.8-26.4) than among girls (paternal exposure OR = 1.31, 95% CI 0.4-4.1; maternal exposure OR = 2.03, 95% CI 0.5-8.9).

Nonsense-mediated mRNA decay in Xenopus oocytes and embryos.

Mutant mRNAs carrying a premature stop codon have a reduced half-life in the cells of many species, probably due to the presence of "surveillance" pathways, which selectively target such mRNAs for degradation. It is reported here that this phenomenon may also occur in Xenopus. In vitro-synthesised transcripts encoding a Xenopus POU-domain protein, XLPOU-60, are stable after injection into the oocyte and embryo. However, introduction of a premature stop codon into these transcripts results in their rapid degradation following injection. In contrast, mutant transcripts with additional or deleted codons but retaining a correct reading frame are stable. These results suggest that RNA stability should be considered when designing control mRNAs for Xenopus injection experiments.

Smoking among oral contraceptive users in Quebec in 1987.

To determine whether an association exists between oral contraceptive (OC) use and cigarette smoking, the data base of the 1987 Québec Health Survey, a cross-sectional study of a provincial population, was sampled to provide a self-weighted subsample. This study population consisted of 292 OC users and a comparison group of 294 non-users, who would have been eligible to use OCs by virtue of their lacking contraindications to their use. 50.5% (95% CI: 44.8%-56.2%) of OC users smoked, as opposed to 41.0% (95% CI: 35.3%-46.7%) of non-users. There was a significant association between OC use and smoking; crude OR = 1.47, 95% CI: 1.06-2.04, p = 0.02. Controlling for effect modifiers and confounders by logistic regression revealed that the positive association prevails mainly in younger married, separated, and single women, whereas in women over 30 and cohabiting women the association is negative. While the negative association in women over 30 may reflect the efforts of physicians to prevent the adverse interactions between OC use and smoking by preventing older smokers from using OCs, the positive association in younger women indicates that physicians may be unable to prevent younger OC users from smoking.