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One hundred seventy-five women 49-65 y old with Wolfe's P2 or DY mammographic patterns were randomly assigned to receive an isoflavone tablet (40 mg isoflavones; Promensil; Novogen Ltd., Stamford, CT) or placebo daily for 1 y. The primary outcome was mammographic breast density; secondary outcomes were circulating levels of estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Women taking hormone replacement therapy or with previous breast cancer or breast surgery were ineligible. The percentage densities on mammograms at recruitment and after 1 y of intervention were visually estimated. Estradiol, FSH and LH were measured in fasting blood samples taken at baseline and 1 y; hormonal changes were assessed only in postmenopausal women. There were no baseline differences between treatment groups. At 1 y, breast density in postmenopausal women and in pre- and perimenopausal women (combined into one group) had decreased in both treatment groups but differences between treatments were not significant (P > 0.01). When divided into tertiles of age, there was a significantly greater decrease in breast density in the isoflavone group than in the placebo group among women in the highest tertile of age (56-65 y; P < 0.05). Among postmenopausal women, estradiol increased nonsignificantly in both treatment groups but the difference between treatments was not significant (P > 0.05). FSH and LH decreased significantly in both treatment groups but changes did not differ significantly between treatments (P > 0.05). In conclusion, and in contrast with hormone replacement therapy, clover-derived isoflavones did not increase breast density; a significant reduction in density was seen in women aged 56-65 y. However, sample sizes within tertiles of age were small and a larger study is needed to confirm these findings. There were no treatment effects for estradiol, FSH or LH in postmenopausal women.

Abstract: Prospective phytoestrogen exposure was assessed using both biomarkers and estimates of intake in 89 British men recruited into the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition study, men who subsequently developed prostate cancer. Results were compared with those from 178 healthy men matched by age and date of recruitment. Levels of seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in spot urine and serum samples. Five single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genes were genotyped. Urinary levels of all phytoestrogens correlated strongly with serum levels. Correlation coefficients ranged from 0.63 (glycitein) to 0.88 (daidzein) ( P < 0.001). Urinary and serum levels correlated significantly with isoflavone intake assessed from food diaries (R = 0.15–0.20; P < 0.05) but not with that from a food-frequency questionnaire. Odds ratios for phytoestrogen exposure, as assessed using the four methods, were not significantly associated with prostate cancer risk ( P = 0.15–0.94). Men with the CC genotype for the ESRI PvuII polymorphism had significantly higher risk for prostate cancer compared with men with the TT genotype [adjusted odds ratio = 4.65 (1.60–13.49); P = 0.005]. Our results utilizing a combined prospective exposure provide no evidence that phytoestrogens alter prostate cancer risk in British men, whereas the C allele for the PvuII polymorphism may be associated with increased risk. [ABSTRACT FROM AUTHOR]

A response by Arjen Dondorp, Nick White and Nick Day to a letter to the editor about their article " "Estimation of the Total Parasite Biomass in Acute Falciparum Malaria From Plasma," in a 2005 issue is presented.

Background: Plasmodium vivax malaria accounts for approximately 60% of malaria cases in Kolkata, India. There has been limited information on the genotypic polymorphism of P. vivax in this malaria endemic area. Three highly polymorphic and single copy genes were selected for a study of genetic diversity in Kolkata strains. Methods: Blood from 151 patients with P. vivax infection diagnosed in Kolkata between April 2003 and September 2004 was genotyped at three polymorphic loci: the P. vivax circumsporozoite protein (pvcs), the merozoite surface protein 1 (pvmsp1) and the merozoite surface protein 3- lpha (pvmsp3-alpha). Results: Analysis of these three genetic markers revealed that P. vivax populations in Kolkata are highly diverse. A large number of distinguishable alleles were found from three genetic markers: 11 for pvcs, 35 for pvmsp1 and 37 for pvmsp3-alpha. These were, in general, randomly distributedamongst the isolates. Among the 151 isolates, 142 unique genotypes were detected the commonest genotype at a frequency of less than 2% (3/151). The overall rate of mixed genotype infections was 10.6%. Conclusion: These results indicate that the P. vivax parasite population is highly diverse in Kolkata, despite the low level of transmission. The genotyping protocols used in this study may be useful for differentiating re-infection from relapse and recrudescence in studies assessing of malarial drug efficacy in vivax malaria. [ABSTRACT FROM AUTHOR]

Phytoestrogens have been hypothesized to protect against prostate cancer via modulation of circulating androgen concentrations. We conducted a cross-sectional study of 267 men in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with 2 aims: first, to investigate the association between phytoestrogen exposure (measured from diet, urine, and serum) and plasma concentrations of sex hormone-binding globulin (SHBG), androstanediol glucuronide, testosterone and Free Androgen Index (FAI); and second, whether the association may be modified by polymorphisms in CYP19 and SHBG genes. Dietary daidzein and genistein intakes were obtained from food diaries and computed using an in-house food composition database. Urinary and serum concentrations of 3 isoflavones (daidzein, genistein, glycitein), 2 daidzein metabolites O-desmethylangolensin (O-DMA) and 2 lignan metabolites (enterodiol and enterolactone) were measured using mass spectrometry. There was no association between dietary, urinary, and serum phytoestrogens and plasma SHBG concentrations. Enterolactone was positively associated with plasma androstanediol glucuronide concentrations (urinary enterolactone: r = 0.127, P = 0.043; serum enterolactone: r = 0.172, P = 0.006) and FAI (urinary enterolactone: r = 0.115, P = 0.067; serum enterolactone: r = 0.158, P = 0.011). Both urinary and serum equol were associated with plasma testosterone (urinary equol: r = 0.332, P = 0.013; serum equol: r = 0.318, P = 0,018) and FAI (urinary equol: r 0.297, P = 0.027; serum equol: r = 0.380, P = 0.004) among men with the TT genotype but not the CC or CT genotypes (r = -0.029 to -0.134, P = 0.091-0.717) for the CYP19 3'untranslated region (UTR) T-C polymorphism. Urinary and serum enterolactone showed similar genotype-dependent associations with testosterone but not with FAI. In this first study on phytoestrogen-gene associations in men, we conclude that enterolactone and equol are positively associated with plasma androgen concentrations, and interactions with CYP19 gene may be involved. [ABSTRACT FROM AUTHOR]

Objective To propose principles of design and measures of effect for cancer screening as a public health policy. Material Finnish routine screening programme with mammography. Design Evaluation of mortality from breast cancer by before-after time trends among Finnish women, by geographical (by municipalities) comparisons, and by intention to screen at an individual level with individual controls who were cluster randomised and matched for age. Outcome measuresStandardised mortality ratios (SMRs) from breast cancer (total), SMRs from breast cancers diagnosed during the screening programme (refined), deaths prevented, prolongation of life for each breast cancer detected, for each death prevented, for each compliant woman, for each screen, and for each invitation. Relative prolongation of life—that is, time gained versus time spent. Results SMRs only at an individual level with deaths from cancers diagnosed during the screening programme and individually selected controls showed 24% protection, whereas the other SMR measures were too crude or biased because of dilution and selection. Prolongation of life varied from 15 years for each death prevented to two days for each woman screened, with approximation for the prolongation relative to time spent of 3 to 1. Conclusions A public health policy should be introduced gradually. Those not covered immediately by the policy serve as controls and they should be randomly allocated. The most relevant outcome measure is prolongation of life, and for public health purposes it should be given per unit of intervention, such as screen or invitation, and also related to the time spent for the intervention. Such gains are often small in a Western society, which implies that medicine, including research, should focus more on other aspects of life than length. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact of the National Health Service breast screening programme on overall and stage-specific incidence of breast cancer in East Anglia; also, to predict the magnitude of the screening induced reduction in breast cancer mortality. Setting Women resident in East Anglia aged 50–69, diagnosed between 1976 and 1995. Methods Comparison of numbers and incidence of breast cancer by age, stage, and mode of detection; investigation of relative contributions of advanced (stages II, III, and IV) cancers to total incidence by detection mode; estimation of the reduction in advanced cancer incidence. Results There has been a large increase in early stage incidence in the age group 50–64 targeted by the screening programme. By 1995, the estimated decrease in advanced cancer incidence was between 7 and 19%. In 1995, of all breast cancers arising in the age group 50–69 years, 33% were screen detected, 27% were interval cancers, 15% were in non-attenders, 9% were in lapsed attenders, 7% occurred before invitation, and 4% arose in women outside the birth year range for invitation. Of the advanced cancers diagnosed in 1995, 31% were interval cancers, 20% were screen detected, 19% were in non-attenders, 12% were in lapsed attenders, 8% occurred before invitation, and 4% presented in women outside the birth year range for invitation. Conclusions Screening has brought about a large increase in detection of early stage cancers. This increase has not yet been fully matched by a corresponding deficit in advanced cancers, possibly because the full effect of screening has not yet been achieved. Reducing the proportion of interval cancers is necessary to increase the effect of screening on mortality. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to an article about the relation between childhood cancer and the distance of birth residence to high voltage power lines.

Recently, we completed a second biostatistical study of urinary tract tumors (UTT) in areas with Balkan endemic nephropathy (BEN) in the Vratza district, Bulgaria, during the period 1975 to 1991. We confirmed the positive correlation between the incidence of urinary tract tumors (UTT) and BEN demonstrated in our first population-based case control 1977 study. A UTT incidence of 98.9 per 100,000 men and 74.7 per 100,000 women was found in villages most affected by BEN when compared with 11.0 and 6.7 for men and women, respectively, in nonendemic villages. The relative risk (RR) of UTT in BEN villages showed tumorsof kidney pelvis and ureters 29 in men and 35 in women and urinary bladder tumors 4 in men and 11 in women. The percentage of food andblood samples containing nephrotoxic and carcinogenic mycotoxin Ochratoxin A (OTA) correlated with the origin of the samples. The most contaminated samples were found in BEN villages and households, and theurinary excretion of OTA was higher in the group of BEN/UTT patients. The UT`T DNAs were studied by the32P-postlabeling methodfor the presence of OTA-DNA adducts. Some OTA-DNA adducts characteristic for endemic UTT and absent in control nonendemic UTT and nontumorous el tissues were described for the first time. [ABSTRACT FROM AUTHOR]