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Biomedical subjects

Franco Berrino

Publications and source records attributed to Franco Berrino.

At least 55 records · Page 3Linked to original sources

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.

Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.

Adult↗

Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.

Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.

Adult↗

Fruits and vegetables and lung cancer: Findings from the European Prospective Investigation into Cancer and Nutrition.

Intake of fruits and vegetables is thought to protect against the development of lung cancer. However, some recent cohort and case-control studies have shown no protective effect. We have assessed the relation between fruit and vegetable intake and lung cancer incidence in the large prospective investigation on diet and cancer, the European Prospective Investigation Into Cancer and Nutrition (EPIC). We studied data from 478,021 individuals that took part in the EPIC study, who were recruited from 10 European countries and who completed a dietary questionnaire during 1992-1998. Follow-up was to December 1998 or 1999, but for some centres with active follow-up to June 2002. During follow-up, 1,074 participants were reported to have developed lung cancer, of whom 860 were eligible for our analysis. We used the Cox proportional hazard model to determine the effect of fruit and vegetable intake on the incidence of lung cancer. We paid particular attention to adjustment for smoking. Relative risk estimates were obtained using fruit and vegetable intake categorised by sex-specific, cohort-wide quintiles. After adjustment for age, smoking, height, weight and gender, there was a significant inverse association between fruit consumption and lung cancer risk: the hazard ratio for the highest quintile of consumption relative to the lowest being 0.60 (95% Confidence Interval 0.46-0.78), p for trend 0.0099. The association was strongest in the Northern Europe centres, and among current smokers at baseline, and was strengthened when the 293 lung cancers diagnosed in the first 2 years of follow-up were excluded from the analysis. There was no association between vegetable consumption or vegetable subtypes and lung cancer risk. The findings from this analysis can be regarded as re-enforcing recommendations with regard to enhanced fruit consumption for populations. However, the effect is likely to be small compared to smoking cessation.

Adult↗

Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC).

We examined the association between self-reported consumption of fruits and vegetables and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow-up for cancer incidence were available for 130544 men in 7 countries recruited into EPIC between 1993 and 1999. After an average of 4.8 years of follow-up, there were 1104 incident cases of prostate cancer. The associations of consumption of total fruits, total vegetables, cruciferous vegetables and combined total fruits and vegetables with prostate cancer risk were examined using Cox regression, stratified for recruitment center and adjusted for height, weight and energy intake. There was a wide range in consumption of fruits and vegetables: mean intakes (g/day) in the bottom and top fifths of the distribution, as estimated from 24-hr recalls in a subsample of participants, were 53.2 and 410.7 for fruits, 97.1 and 242.1 for vegetables and 169.0 and 633.7 for fruits and vegetables combined. No significant associations between fruit and vegetable consumption and prostate cancer risk were observed. Relative risks (95% confidence intervals) in the top fifth of the distribution of consumption, compared to the bottom fifth, were 1.06 (0.84-1.34) for total fruits, 1.00 (0.81-1.22) for total vegetables and 1.00 (0.79-1.26) for total fruits and vegetables combined; intake of cruciferous vegetables was not associated with risk. These results suggest that total consumption of fruits and vegetables is not associated with the risk for prostate cancer.

Adult↗

Dietary patterns and risk of breast cancer in the ORDET cohort.

The aim of this study was to evaluate the association between dietary patterns and risk of developing breast cancer in an Italian cohort. Women volunteers were recruited from 1987 to 1992 from residents in Varese province, northern Italy, an area covered by a cancer registry. Participants completed a semiquantitative food frequency questionnaire, and anthropometric and other data were collected systematically. Using nutritional data from 8984 women with an average follow up of 9.5 years and 207 incident cases of breast cancer, we conducted an exploratory factor analysis to identify major dietary patterns. Four dietary patterns, which explained 30% of the variance, emerged: salad vegetables (mainly consisting of raw vegetables and olive oil); western (mainly consisting of potatoes, red meat, eggs and butter); canteen (pasta and tomato sauce); and prudent (cooked vegetables, pulses, and fish, with negative loading on wines and spirits). After adjustment for potential confounders, only the salad vegetables pattern was associated with significantly lower (34-35%) breast cancer incidence (RR = 0.66, CI(95%) = 0.47+/-0.95 comparing highest with lowest tertile) with a significant linear trend (P = 0.016). Women with body mass index <25 had an even greater risk reduction in the highest tertile of the salad vegetables pattern (>50% less risk than the lowest tertile, RR = 0.39, CI(95%) = 0.22-0.69) with a significant trend (P = 0.001); whereas women with body mass index > or =25 had no protective effect for the consumption of salad vegetables. These findings suggest that a diet rich in raw vegetables and olive oil protects against breast cancer.

Adult↗

Circulating soluble Fas levels and risk of ovarian cancer.

BACKGROUND: Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. METHODS: The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. RESULTS: Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4-10.2) and in controls (median, 6.8 ng/mL; range, 4.5-10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42-1.82). CONCLUSION: The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer.

Biomarkers, Tumor↗

Stage at diagnosis is a key explanation of differences in breast cancer survival across Europe.

We used multiple regression models to assess the influence of disease stage at diagnosis on the 5-year relative survival of 4,478 patients diagnosed with breast cancer in 1990-1992. The cases were representative samples from 17 population-based cancer registries in 6 European countries (Estonia, France, Italy, Netherlands, Spain and UK) that were combined into 9 regional groups based on similar survival. Five-year relative survival was 79% overall, varying from 98% for early, node-negative (T1N0M0) tumours; 87% for large, node-negative (T2-3N0M0) tumours; 76% for node-positive (T1-3N+M0) tumours and 55% for locally advanced (T4NxM0) tumours to 18% for metastatic (M1) tumours and 69% for tumours of unspecified stage. There was considerable variation across Europe in relative survival within each disease stage, but this was least marked for early node-negative tumours. Overall 5-year relative survival was highest in the French group of Bas-Rhin, Côte d'Or, Hérault and Isère (86%), and lowest in Estonia (66%). These geographic groups were characterised by the highest and lowest percentages of women with early stage disease (T1N0M0: 39% and 9%, respectively). The French, Dutch and Italian groups had the highest percentage of operated cases. The number of axillary nodes examined, a factor influencing nodal status, was highest in Italy and Spain. After adjusting for TNM stage and the number of nodes examined, survival differences were greatly reduced, indicating that for these women, diagnosed with breast cancer in Europe during 1990-1992, the survival differences were mainly due to differences in stage at diagnosis. However, in 3 regional groups, the relative risks of death remained high even after these adjustments, suggesting less than optimal treatment. Screening for breast cancer did not seem to affect the survival patterns once stage had been taken into account.

Adenocarcinoma↗

Circulating levels of sex steroid hormones and risk of ovarian cancer.

Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre-diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case-control study nested within 3 cohorts, in New York (USA), Umeå (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81-6.82.), but the small number of subjects in the sub-group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk.

Adult↗

Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in an international case-control study in France, Italy, Spain and Switzerland.

OBJECTIVE: To investigate the effect of exposure to occupational agents on the risk of hypopharyngeal/laryngeal cancer. METHODS: Case-control study conducted during 1979-1982 in six centres in South Europe. An occupational history and information on exposure to non-occupational factors were collected for 1010 male cases of hypopharyngeal/ laryngeal cancer as well as for 2176 population controls. The exposure to 10 occupational agents was assessed through a job-exposure matrix. As occupational histories had been collected since 1945 major analyses were restricted to subjects aged less than 55 years (315 cases and 819 controls). RESULTS: Significant elevated risks adjusted for non-occupational variables (smoking, alcohol consumption and diet) and other occupational exposures were consistently found for organic solvents (odds ratio (OR) for ever-exposure: 1.7, 95% confidence interval: 1.1-2.5) and asbestos (OR: 1.6, 1.0-2.5). A significant positive trend for both probability of exposure and duration was found for exposure to solvents. A positive association between exposure to formaldehyde and laryngeal cancer was also suggested. No association was found for exposure to arsenic and compounds, chromium and compounds, and polycyclic aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7). CONCLUSIONS: In our study occupational exposure to solvents was associated with an increased risk of hypopharyngeal/laryngeal cancer. Results also provide additional evidence of an excess of risk for exposure to asbestos.

Adult↗

Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).

OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.

Adult↗

Occupation and larynx and hypopharynx cancer: an international case-control study in France, Italy, Spain, and Switzerland.

OBJECTIVE: To estimate risks for laryngeal/hypopharyngeal cancer associated with occupational titles and industrial activities. METHODS: A multicentre population-based case-control study was conducted in the early 1980s in six southern European areas. Analyses included 1010 male cases and 2176 controls. Odds ratios (ORs) (adjusted for age, study area, tobacco consumption, and alcohol consumption) were estimated for 156 occupations and 70 industrial activities. RESULTS: An excess risk has been confirmed for categories of construction workers, potters (OR: 5.91, 95% confidence intervals 1.46-24.0), butchers (2.53, 1.22-5.22), barbers (2.33, 1.00-5.40), laborers not otherwise specified (1.52, 1.12-2.06), as well as for men who had been employed in railway transport (1.52, 0.97-2.39), shipbuilding (2.05, 0.89-4.94), and hotels (2.06, 0.89-4.75). An association was also found for shoe finishers (3.23, 0.75-13.9), loggers (2.07, 0.87-4.90), and some groups of metal workers. ORs for loggers, butchers, railway transport workers, laborers, and reinforced concreters increased with duration of employment. The suggestion of a risk for machine operators among woodworkers (3.10, 0.92-10.5) conflicts with previous findings. No significant excess of risk was found for categories previously reported to be associated with laryngeal and hypopharyngeal cancer, such as drivers, mechanics, welders, machinists, and painters. CONCLUSIONS: The present study provides additional evidence to the hypothesis of a risk of cancer of the larynx/ hypopharynx for workers engaged in jobs in the construction, metal, textile, ceramic, and food industries and in railway transport. Loggers were also found at risk; a previously unreported finding.

Adolescent↗

Pleural mesothelioma incidence in Europe: evidence of some deceleration in the increasing trends.

OBJECTIVE: To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries. MATERIAL AND METHODS: The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40-74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986-1990 and 1991-1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988-1997) were compared with trends in the previous decade. Fitted rates in younger (40-64) and older adults (65-74) in the most recent period were also compared. RESULTS: There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings. CONCLUSIONS: While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.

Asbestos↗

Women's perception of the benefits of mammography screening: population-based survey in four countries.

BACKGROUND: Screening programmes are often actively promoted to achieve high coverage, which may result in unrealistic expectations. We examined women's understanding of the likely benefits of mammography screening. METHODS: Telephone survey of random samples of the female population aged > or =15 years in the US, UK, Italy, and Switzerland using three closed questions on the expected benefits of mammography screening. RESULTS: A total of 5964 women were contacted and 4140 women (69%) participated. Misconceptions were widespread: a majority of women believed that screening prevents or reduces the risk of contracting breast cancer (68%), that screening at least halves breast cancer mortality (62%), and that 10 years of regular screening will prevent 10 or more breast cancer deaths per 1000 women (75%). In multivariate analysis higher number of correct answers was positively associated with higher educational status (odds ratio [OR] = 1.44, 95% CI: 1.25, 1.66) and negatively with having had a mammography in the last 2 years (OR = 0.86, 95% CI: 0.73, 1.01). Compared with US women (reference group) and Swiss women (OR = 0.98, 95% CI: 0.82, 1.18) respondents in Italy (OR = 0.61, 95% CI: 0.50, 0.74) and the UK (OR = 0.73, 95% CI: 0.60, 0.88) gave fewer correct answers. CONCLUSION: In the US and three European countries a high proportion of women overestimated the benefits that can be expected from screening mammography. This finding raises doubts on informed consent procedures within breast cancer screening programmes.

Adolescent↗

Common and country-specific dietary patterns in four European cohort studies.

The association between diet and cancer, predominantly investigated univariately, has often been inconsistent, possibly because of the large number of candidate risk factors and their high intercorrelations. Analysis of dietary patterns is expected to give more insight than analysis of single nutrients or foods. This study aimed to develop and apply a common methodological approach to determine dietary patterns in four cohort studies originating in Finland, the Netherlands, Sweden and Italy. Food items on each of the food frequency questionnaires were aggregated into 51 food groups, defined on the basis of their position in the diet pattern and possible relevance to cancer etiology. Exploratory factor analysis was used to analyze dietary patterns. Using a standardized approach, 3-5 stable dietary patterns were identified, explaining 20-29% of total variance in consumption of the food groups. Two dietary patterns, which explained most of the variance, were consistent across the studies. The first pattern was characterized by high consumption of (salad) vegetables, the second by high consumption of pork, processed meat and potatoes. In addition, a few specifically national food patterns were identified. Sensitivity analyses showed that the identified patterns were robust for number of factors extracted, distribution of input variables and energy adjustment. Our findings suggest that some important eating patterns are shared by the four populations under study, whereas other eating patterns are population specific.

Adult↗

A plant food-based diet modifies the serum beta-sitosterol concentration in hyperandrogenic postmenopausal women.

Plant sterols or phytosterols are common components of plant foods, especially plant oils, seeds and nuts, cereals and legumes. The most common phytosterols are campesterol, beta-sitosterol and stigmasterol. Phytosterols have anticarcinogenic properties. Previous studies have suggested that populations with low breast cancer incidence often consume diets high in phytosterols. The present study evaluated whether consumption of a plant food-based diet, low in animal fat, may increase serum phytosterol levels in postmenopausal women. One hundred and four women volunteers were randomized to dietary intervention or control groups. The dietary intervention included intensive dietary counseling to replace animal products with plant-based foods. Subjects in the dietary intervention group participated twice a week for 18 wk in workshops about the preparation and consumption of a plant food-based diet. The absolute change in serum total phytosterol concentration was greater in the dietary intervention group than in the control group. The percent change tended to differ between groups (P = 0.06). However, only for beta-sitosterol did the absolute and percent changes within a group differ significantly between groups (P = 0.0017). The decrease in serum total cholesterol in the dietary intervention group (-14%) was greater than that in the control group (-4%; P = 0.0005). The results of this study show that circulating levels of phytosterols can be affected by dietary modification. These findings indicate that phytosterols, in particular beta-sitosterol, can be used as biomarkers of exposure in observational studies or as compliance indicators in dietary intervention studies of cancer prevention.

Cholesterol↗

Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study.

Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. We investigated the role of SNPs in three DNA repair genes (X-ray repair cross-complementing group 1-Arg399Gln, exon 10; X-ray repair cross-complementing group 3-Thr241Met, exon 7; and xeroderma pigmentosum-D-Lys751Gln, exon 23) and their combination, in modulating the levels of "bulky" DNA adducts in a population sample of 628 Italian healthy individuals belonging to the prospective European project "European Prospective Investigation into Cancer and Nutrition." DNA-adduct levels were measured as relative adduct level per 10(9) nucleotides by (32)P-post DNA labeling assay in WBCs from peripheral blood. Genotyping was performed by PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. We found a dose-response relationship between the number of at-risk alleles and levels of adducts (P = 0.0046). Individuals with at least three variant alleles had a statistically significant odds ratio (OR) for being in the highest tertile of adducts compared with those with undetectable adducts [three alleles, adjusted OR = 5.07, 95% confidence interval (CI) = 1.29-19.9; four alleles, adjusted OR = 5.03, 95% CI = 1.18-21.45; five alleles, adjusted OR = 7.65, 95% CI = 0.94-62.2]. Our study suggests that the combined effect of multiple variant alleles may be more important than the investigation of single SNP in modulating DNA repair capacity.

Alleles↗

Toenail selenium as biomarker: reproducibility over a one-year period and factors influencing reproducibility.

We assessed the reproducibility of selenium levels in toenails, comparing concentrations in two sets of specimens collected about a year apart, from 80 women (40 pre-menopausal and 40 post-menopausal) in the period October 1990 to February 1992. The women were participants in a prospective study on hormones and diet in relation to prediagnostic breast cancer (the ORDET study) conducted in northern Italy. Toenail selenium was determined by electrothermal atomic absorption spectrometry. The data were log-transformed as they were not normally distributed. To assess reproducibility Pearson correlation coefficients (r) for the two selenium determinations were calculated in pre- and post-menopausal women, according to smoking status and acetone treatment. A weighted kappa statistic (k) assessed inter-quintile agreement between the two sets of measures. Toenail selenium levels were highly reproducible (r = 0.57, p < 0.001), especially in pre-menopausal women (r = 0.66, p <0.001). Smoking lowered selenium levels (mean difference of 0.24 microg/g, p < 0.05 between smokers and non smokers) but did not significantly influence reproducibility. Acetone treatment to remove nail polish did not modify selenium levels but affected inter-quintile agreement, with moderate agreement (k = 0.58, p < 0.001) when acetone was used at both or neither samplings; and fair non significant agreement (k = 0.39, p = 0.06) when acetone was used at one sampling but not the other. As selenium levels in toenails are highly reproducible, notwithstanding variation in selenium levels in food and long-term changes in individuals' food choices, toenail selenium may be a useful biomarker of selenium exposure, particularly since toenail samples provide a measure of long-term exposure. However age, smoking status and acetone treatment are possible causes of misclassification.

Acetone↗