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P Toniolo

Publications and source records attributed to P Toniolo.

At least 19 recordsLinked to original sources
PubMed2004

Circulating enterolactone and risk of breast cancer: a prospective study in New York.

It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.

4-Butyrolactone↗
PubMed2004

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study.

We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production.

Aged↗
PubMed2004

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Adult↗
PubMed2003

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aged↗
PubMed2002

Aspirin and lung cancer in women.

The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type.

Adult↗
PubMed2001

Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: the gonadotropin hypothesis revisited.

The gonadotropin hypothesis postulates that excessive gonadotropin stimulation results in increased proliferation and subsequent malignant transformation of ovarian epithelium. The authors evaluated this hypothesis by analyzing the association between serum levels of wild-type luteinizing hormone (LH) and ovarian cancer risk. They also examined the relation between a variant of LH containing two missense point mutations (Trp(8)Arg and Ile(15)Thr) in its beta-subunit and ovarian cancer risk. Fifty-eight cases of epithelial ovarian cancer and 116 controls matched on age, menopausal status, and date of blood donation were included in a case-control study nested within the New York University Women's Health Study, a prospective cohort enrolled between 1985 and 1991 in New York City. Wild-type serum levels and variant LH status were determined by immunofluorometric assays in which monoclonal antibodies specific for wild-type and variant LH were used. Compared with women in the lowest tertile of wild-type LH, women in the highest tertile had a lower risk of ovarian cancer, after adjustment for potential confounders (odds ratio = 0.42, 95% confidence interval: 0.09, 2.09). Women heterozygous for variant LH were not at increased risk (adjusted odds ratio = 0.95, 95% confidence interval: 0.27, 3.34). The results suggest that neither wild-type LH levels nor variant LH status is associated with increased risk of epithelial ovarian cancer.

Adult↗
PubMed2001

A prospective study of insulin-like growth factor-I, IGF-binding proteins-1, -2 and -3 and lung cancer risk in women.

Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic properties and has been implicated in the development of breast, colorectum, prostate and lung cancer. IGF binding proteins (IGFBPs) are not only carrier proteins for IGFs but also hold a central position in IGF ligand-receptor interactions through influences on the bioavailability and distribution of IGFs in the extracellular environment. A case-control study nested within the New York University Women's Health Study Cohort included 93 women diagnosed with lung cancer at least 6 months after recruitment into the study. Two controls (n = 186) were matched to each case on age, date of blood sampling, menopausal status, day of menstrual cycle and questionnaire data of smoking status at the time of blood donation. Serum IGF-I, IGFBP-1, -2 and -3, insulin and cotinine were measured. Mean serum levels of IGF-I, IGFBP-1, -2 and -3 were not significantly different between the case and control groups. Univariate logistic regression analyses showed no association of lung cancer risk with serum levels of IGF-I or any of the IGFBPs. These results remained virtually the same in multivariate analyses, including adjustment for cotinine, time since last meal, BMI, IGF-I or IGFBP-3, respectively. Exclusion of cases diagnosed within 3 years of recruitment in the cohort, or restriction of the analyses to adenocarcinomas only, did not alter these results. Our study does not offer evidence in support of an association between prediagnostic serum levels of IGF-I or IGFBP-1, -2 and -3 and lung cancer risk in women.

Adult↗
PubMed2001

Serum carotenoids and breast cancer.

The consumption of vegetables and fruit may protect against many types of cancer, but research evidence is not compelling for breast cancer. Carotenoids are pigments that are present in most plants and have known antioxidant properties. Blood concentrations of carotenoids have been proposed as integrated biochemical markers of vegetable, fruit, and synthetic supplements consumed. In a case-control study (270 cases, 270 controls) nested within a cohort in New York during 1985-1994, the carotenoids lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene were measured in archived serum samples using liquid chromatography. There was an evident increase in the risk of breast cancer for decreasing beta-carotene, lutein, alpha-carotene, and beta-cryptoxanthin. The risk of breast cancer approximately doubled among subjects with blood levels of beta-carotene at the lowest quartile, as compared with those at the highest quartile (odds ratio = 2.21; 95% confidence interval (CI): 1.29, 3.79). The risk associated with the other carotenoids was similar, varying between 2.08 (95% CI: 1.11, 3.90) for lutein and 1.68 (95% CI: 0.99, 2.86) for beta-cryptoxanthin. The odds ratio for the lower quartile of total carotenoids was 2.31 (95% CI: 1.35, 3.96). These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes.

Adult↗
PubMed2001

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Breast Neoplasms↗
PubMed2001

Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study.

We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median of 5.5 years after blood donation. Each case was compared to 4 controls matched on age, menopausal status at enrolment, and serum storage duration. Endometrial cancer risk increased with higher levels of oestradiol (odds ratio = 2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR = 0.39, P = 0.01). Trends remained in the same directions after adjusting for height and body mass index. A positive association of body mass index with risk was substantially reduced after adjusting for oestrone level. Our results indicate that risk of endometrial cancer increases with increasing postmenopausal oestrogen levels but do not provide strong support for a role of body mass index independent of its effect on oestrogen levels.

Adult↗
PubMed2001

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies.

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

Adult↗
PubMed2001

Aspirin and epithelial ovarian cancer.

BACKGROUND: Epidemiological evidence suggests that chronic inflammation may influence ovarian carcinogenesis. The study objective was to examine the association between the commonly used anti-inflammatory drug aspirin and epithelial ovarian cancer. METHODS: The authors conducted a case-control study based in the New York University Women's Health Study cohort enrolled between 1985 and 1991 in New York City. After a median follow-up period of 12 years, 68 incident cases of epithelial ovarian cancer were identified. Data about regular aspirin use were collected during the 1994-1996 follow-up questionnaire. Using a case-control study design, 10 controls per case were randomly selected among study participants who matched the case by age and menopausal status. Conditional logistic regression analysis was used to study the relationships between aspirin and epithelial ovarian cancer by generating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Relative to no aspirin use, the OR for epithelial ovarian cancer among women who reported aspirin use three or more times per week for a period of at least 6 months was 0.60 (95% CI 0.26, 1.38), after adjustment for age at menarche, parity, oral contraceptive use, and first-degree family history of breast cancer before age 50. Among recent, within the previous 5 years, users of aspirin, the adjusted OR was 0.36 (95% CI 0.11, 1.18). CONCLUSION: Although confidence intervals included unity, the observed risk estimates seem to be compatible with previous studies suggesting that regular aspirin use could be inversely associated with risk of epithelial ovarian cancer.

Adult↗
PubMed2001

Serum carotenoids as biomarkers of fruit and vegetable consumption in the New York Women's Health Study.

OBJECTIVE: To investigate the usefulness of serum carotenoids as biomarkers of fruit and vegetable consumption. DESIGN: : Reproducibility study on three repeat measurements of serum carotenoids. Correlation analysis of carotenoids and dietary food intake, and regression analysis of potential predictive parameters for serum carotenoid levels. SETTING: New York, USA. SUBJECT: : Women participating in the New York Women's Health Study, a prospective study of sex hormones, diet and breast cancer. Forty-eight women with three repeat blood samples and 302 women having a blood sample and a dietary history questionnaire (including 47 subjects from the reproducibility study). RESULTS: Serum carotenoid concentrations were highly reproducible between one- and two-year repeat samples. Estimated fruit and vegetable consumption was positively correlated with serum carotenoid concentrations but correlation coefficients were low. Consumption of fruit was predictive for serum levels of beta-carotene, alpha-carotene and beta-cryptoxanthin, while vegetable consumption was predictive for serum beta-carotene, lutein, zeaxanthin and lycopene. Serum concentrations of cholesterol and triglycerides were predictive for serum carotenoids but adjustment for their levels had little or no influence on the correlation between fruit and vegetable consumption and serum carotenoid concentrations. CONCLUSIONS: One single serum measurement of alpha-carotene, beta-carotene and lutein can accurately rank subjects according to their usual serum level. Serum concentrations, however, correlate only moderately with estimated dietary intake of fruits or vegetables and should therefore be used with caution as biomarkers of fruit and vegetable intake.

Biomarkers↗
PubMed2001

A cross-sectional study of IGF-I determinants in women.

Evidence is accumulating that elevated circulating insulin-like growth factor I (IGF-I) is related to increased cancer risk. The identification of hormonal, reproductive and lifestyle characteristics influencing its synthesis and bioavailability is of particular interest. Data from 400 women, who served as controls in two case-control studies nested within the same prospective cohort study, were combined. IGF-I, IGF-binding proteins 1, 2 and 3 (IGFBP-1, -2, -3) and insulin were measured in serum samples from all subjects and cotinine in 186 samples. Age appears to be the most important determinant of total IGF-I levels in women. Anthropometric measures, such as body mass index (BMI) or waist-to-hip ratio (WHR) do not seem to influence total IGF-I concentrations in peripheral blood, but may modulate IGF-I bioavailability through insulin-dependent changes in IGFBP-1 and -2 concentrations. Age at menarche, phase of the menstrual cycle at blood draw, parity, menopause, past oral contraceptive or hormone replacement therapy use, and tobacco smoking do not appear to exert an independent effect on IGF-I and its binding proteins. There was some suggestion that regular physical activity may increase total IGF-I and that women with positive family history of breast cancer might have higher IGF-I levels than those without such diagnosis in their relatives.

Age Factors↗
PubMed2001

Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives.

Endometrial carcinoma is the most common cancer of the female reproductive organs in the United States. International comparisons reveal that the incidence of endometrial cancer vary widely between different countries with the highest rates observed in North America and Northern Europe, intermediate rates in Eastern Europe and Latin America, and lowest rates in Asia and Africa. International variation in endometrial cancer rates may represent differences in the distribution of known risk factors, which include obesity, postmenopausal estrogen replacement, ovarian dysfunction, diabetes mellitus, infertility, nulliparity, and tamoxifen use. Most of the risk factors for endometrial cancer can be explained within the framework of the unopposed estrogen hypothesis, which proposes that exposure to estrogens unopposed by progesterone or synthetic progestins leads to increased mitotic activity of endometrial cells, increased number of DNA replication errors, and somatic mutations resulting in malignant phenotype. Although the impact of exogenous hormone replacement was intensively studied during the last two decades, less is known about the effects of endogenous hormones in endometrial cancer. A review of available experimental, clinical, and epidemiologic data suggests that in addition to estrogens, other endogenous hormones, including progesterone, androgens, gonadotropins, prolactin, insulin, and insulin-like growth factors, may play a role in the pathogenesis of different histopathologic types of endometrial cancer.

Animals↗
PubMed2001

Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women.

In large-scale epidemiological studies on endogenous sex steroids and cancer risk, direct immunoassays of circulating hormone levels have the advantage of being fast and comparatively inexpensive while requiring only small sample volumes. On the other hand, indirect assays after organic extraction and chromatographic prepurification have the advantage of reducing specific interferences and matrix effects and hence are thought to have better validity. We compared direct assays of testosterone (T, six different assays), Delta4-androstenedione (A, four assays), estrone (E(1), one assay), and 17beta-estradiol (E(2), five assays) with measurements obtained by an indirect assay in a representative subset of 20 postmenopausal women who were part of a large prospective cohort study. Within-batch reproducibilities of the subject rankings by relative hormone levels were good (intraclass correlations >0.89) for all direct assays tested. Between batches, reproducibilities generally were also acceptable (r > 0.80) to good (r > 0.90) in terms of Pearson's correlations. The between-batch reproducibility in terms of intraclass correlations was systematically lower in terms of Pearson's correlations, however, because of between-batch variations in the absolute scale of measurements. The relative validity of direct versus indirect assays in terms of the subjects' ranking by relative hormone levels was also high for most of the kits tested for T, A, and E(1) (Pearson's correlations between 0.70 and 0.89) but was high for only two kits of five tested for E(2) (correlations of 0.86 and 0.84). On an absolute scale, mean measurement values were generally higher for direct assays than for the indirect assay and, for each hormone, varied substantially, depending on the kit used. Overall, the results of this study show that, with careful selection, commercial kits for direct radioimmunoassays of steroid hormones in postmenopausal serum can be found that may allow a reliable estimation of relative risks in epidemiological studies. However, standardization of the absolute scale of assays remains problematic.

Aged↗