Biomedical subjects

Sabina Sieri

Publications and source records attributed to Sabina Sieri.

At least 19 recordsLinked to original sources

PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University Münster.

Journal Article↗

PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

Journal Article↗

PubMed2007

Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

OBJECTIVES: To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach. METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520 000 participants mostly aged 35-70 years. Information on diet and lifestyle was collected at recruitment. After an average follow-up of 6.5 years, 268 cases with adenocarcinoma of the stomach and 56 of the oesophagus were confirmed. We examined the effect of socioeconomic position on cancer risk by means of educational data and a computed Relative Index of Inequality (RII). In a nested case-control study, adjustment for Helicobacter pylori (H. pylori) infection was performed. RESULTS: Higher education was significantly associated with a reduced risk of gastric cancer [vs lowest level of education, hazard ratio (HR): 0.64, 95% Confidence intervals (CI): 0.43-0.98]. This effect was more pronounced for cancer of the cardia (HR: 0.42, 95% CI: 0.20-0.89) as compared to non-cardia gastric cancer (HR: 0.66, 95% CI: 0.36-1.22). Additionally, the inverse association of educational level and gastric cancer was stronger for cases with intestinal (extreme categories, HR: 0.13, 95% CI: 0.04-0.44) rather than diffuse histological subtype (extreme categories, HR: 0.71 95% CI: 0.37-1.40). In the nested case-control study, inverse but statistically non-significant associations were found after additional adjustment for H. pylori infection [highest vs lowest level of education: Odds ratio (OR) 0.53, 95% CI: 0.24-1.18]. Educational level was non-significantly, inversely associated with carcinoma of the oesophagus. CONCLUSION: A higher socioeconomic position was associated with a reduced risk of gastric adenocarcinoma, which was strongest for cardia cancer or intestinal histological subtype, suggesting different risk profiles according to educational level. These effects appear to be explained only partially by established risk factors.

Adenocarcinoma↗

PubMed2007

Development and validation of a food frequency questionnaire for the assessment of dietary total antioxidant capacity.

The total antioxidant capacity (TAC) of the diet may be an important tool to monitor the protective effect of plant foods in epidemiological studies. We developed a semi-quantitative FFQ for the assessment of dietary TAC by 3 different assays, i.e., Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). The FFQ consists of 53 questions about the major sources of dietary TAC in Northern Italy and was validated against a 3-d weighed food record (3D-WR) in 285 individuals (159 males and 126 females) aged 35-88 y and living in the province of Parma (Italy). Plasma TAC was also evaluated in a subgroup of subjects using the TEAC and FRAP assays. The FFQ was associated with 3D-WR (quadratic-weighted kappa = 0.49 for TEAC, 0.53 for TRAP, and 0.49 for FRAP; P < 0.0001) and proved reasonably accurate to classify individuals into quartiles of TAC intake. The FFQ had a good repeatability when readministered after 1 y in 55 subjects (quadratic-weighted kappa for intertertile agreement = 0.66 for TEAC, 0.70 for TRAP and 0.68 for FRAP; P < 0.0001). With both dietary instruments, the main contributors to TAC intake were coffee and tea in women and alcoholic beverages in men, followed by fruits and vegetables in both sexes. Plasma TAC and dietary TAC were not associated. In conclusion, our FFQ has the potential for being used to rank subjects on the basis of their antioxidant intake as determined by dietary TAC in large epidemiological studies. The FFQ should be validated in external populations before being used for research purposes.

Adult↗

PubMed2006

Ethanol intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (> or =60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.

Adult↗

PubMed2006

Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.

Adult↗

PubMed2006

Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).

BACKGROUND: Body weight and body mass index (BMI) are positively related to risk of colon cancer in men, whereas weak or no associations exist in women. This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy (HRT) in women. METHODS: We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospective Investigation Into Cancer and Nutrition. All statistical tests were two-sided. RESULTS: During 6.1 years of follow-up, we identified 984 and 586 patients with colon and rectal cancer, respectively. Body weight and BMI were statistically significantly associated with colon cancer risk in men (highest versus lowest quintile of BMI, relative risk [RR] = 1.55, 95% confidence interval [CI] = 1.12 to 2.15; P(trend) = .006) but not in women. In contrast, comparisons of the highest to the lowest quintile showed that several anthropometric measures, including waist circumference (men, RR = 1.39, 95% CI = 1.01 to 1.93; P(trend) = .001; women, RR = 1.48, 95% CI = 1.08 to 2.03; P(trend) = .008), waist-to-hip ratio (WHR; men, RR = 1.51, 95% CI = 1.06 to 2.15; P(trend) = .006; women, RR = 1.52, 95% CI = 1.12 to 2.05; P(trend) = .002), and height (men, RR = 1.40, 95% CI = 0.99 to 1.98; P(trend) = .04; women, RR = 1.79, 95% CI = 1.30 to 2.46; P(trend)<.001) were related to colon cancer risk in both sexes. The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100,000 men and 129 and 86 cases per 100,000 women in the highest and lowest quintiles of WHR, respectively. Upon further stratification, no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT. None of the anthropometric measures was statistically significantly related to rectal cancer. CONCLUSIONS: Waist circumference and WHR, indicators of abdominal obesity, were strongly associated with colon cancer risk in men and women in this population. The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women; however, these findings require confirmation in future studies.

Abdominal Fat↗

PubMed2006

Fruits and vegetables and renal cell carcinoma: findings from the European prospective investigation into cancer and nutrition (EPIC).

We examined the association between fruits and vegetables and risk of renal cell carcinoma (RCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake data and complete follow-up information on cancer incidence were available for 375,851 participants recruited in EPIC centers of 8 countries. During an average follow-up of 6.2 years, 306 incident cases of RCC were identified. The associations of consumption of total vegetables, total fruits, combined total fruits and vegetables and specific subtypes of vegetables with RCC risk were analyzed using Cox proportional hazards, stratified by centre and adjusted for potential confounders. No significant associations between fruit and vegetable consumption and RCC risk were observed despite a wide range of intake. The estimated relative risks (95% confidence intervals [CI]) in men and women combined were 0.97 (0.85-1.11) per 40 g increase in vegetable intake, 1.03 (0.97-1.08) per 40 g increase in fruit intake and 1.02 (0.93-1.11) per 80 g increase in fruit and vegetable intake combined. Among the vegetable subtypes, an inverse association was observed for root vegetables (RR per 8 g increase: 0.88; 95% CI: 0.78-0.99). These results suggest that total consumption of fruits and vegetables is not related to risk of RCC, although we cannot exclude the possibility that very low consumption is related to higher risk. The relationship of specific fruit and vegetable subgroups with RCC risk warrant further investigation.

Adult↗

PubMed2006

Associations between dietary pattern and lifestyle, anthropometry and other health indicators in the elderly participants of the EPIC-Italy cohort.

INTRODUCTION: Epidemiological studies have shown that dietary behaviour is an important aetiological factor in various chronic diseases. We used principal component factor analysis to identify dietary patterns and to examine the associations of these patterns with health-related variables in a sample of elderly (> or =60 years) Italians participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: Exploratory factor analysis was applied to the intake of food groups as estimated by semi-quantitative food questionnaires. Individual participants were assigned factor scores, indicating the extent to which their diet conformed to each of the four dietary patterns identified: prudent (cooked vegetables, pulses, cabbage, seed oil and fish); pasta & meat (pasta, tomato sauce, red meat, processed meat, bread and wine); olive oil & salad (raw vegetables, olive oil, soup and chicken); and sweet & dairy (sugar, cakes, ice cream, coffee and dairy). Highly educated people had high scores on prudent and low scores on pasta & meat. The pasta & meat and prudent patterns were strongly positively associated with body mass index (BMI) and waist-to-hip ratio (WHR) in men and women. Hyperlipidaemic men and women consumed more of the prudent and olive oil & salad patterns and less of the sweet & dairy pattern than those with normal lipids. The olive oil & salad was significantly higher and the pasta & meat and sweet & dairy patterns significantly lower in men and women who had dieted over the previous year, suggesting awareness of the health consequences of these patterns. CONCLUSIONS: Dietary pattern analysis provides a characterization of recurrent dietary behaviour in elderly people, and can be used to provide tangible dietary advice to elderly people.

Anthropometry↗

PubMed2006

Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 incident cases of RCC. Relative risks were calculated using Cox regression, stratified by age and study center and adjusted for smoking status, education, alcohol consumption, physical activity, menopausal status, and hormone replacement therapy use. Among women, an increased risk of RCC was conferred by body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95% confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94-2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p-trend = 0.01); however, waist and hip circumference were no longer significant after controlling for body weight. Among men, hip circumference (RR = 0.44; 95% CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk only after accounting for body weight. Height was not related significantly to RCC risk. Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women, whereas low hip circumference is related to increased RCC risk among men. Our data give further credence to public health efforts aiming to reduce the prevalence of obesity to prevent RCC, in addition to other chronic diseases.

Body Composition↗

PubMed2006

Protein intake in Parkinsonian patients using the EPIC food frequency questionnaire.

The dietary habits of 45 Italian patients with Parkinson's disease (PD) and their spouses were investigated using the EPIC food frequency questionnaire. Average daily energy intake was similar, but PD patients consumed significantly more vegetable proteins and carbohydrates (both +18%; P = 0.01 and P = 0.001, respectively). Daily protein intake, which interferes with levodopa absorption, was 50% higher than the recommended daily allowance (1.2 vs. 0.8 g/kg) in both PD patients and spouses and was significantly higher in patients with moderate/severe symptoms (1.27 +/- 0.29 vs. 1.07 +/- 0.28 g/kg; P < 0.001). In patients taking levodopa, there was a correlation between daily levodopa dosage and protein intake (P = 0.027). Dietary habits of patients with advanced and/or fluctuating PD should always be checked, with particular reference to protein intake.

Aged↗

PubMed2006

The effect of occasional smoking on smoking-related cancers: in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung. METHODS: The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers. RESULTS: The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93-3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80-1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers. CONCLUSIONS: Occasional smoking should be discouraged.

Adult↗

PubMed2005

Erythrocyte membrane phospholipid composition as a biomarker of dietary fat.

BACKGROUND/AIMS: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. METHODS: Study participants were 204 women, aged 39-65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. RESULTS: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r=0.39, p<0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r=0.21 and r=0.43 (premenopausal), and r=0.41 and r=0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r=0.25, p<0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r=-0.29, p=0.01 and r=-0.22, p<0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r=-024, p<0.05). CONCLUSIONS: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.

Adult↗

PubMed2005

Consumption of vegetables and fruits and risk of breast cancer.

CONTEXT: The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. OBJECTIVE: To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 285,526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. MAIN OUTCOME MEASURES: Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. RESULTS: During 1,486,402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% CI , 0.94-1.25) for total fruit, and 1.05 (95% CI , 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. CONCLUSION: Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.

Adult↗

PubMed2005

Trace elements and melanoma.

Melanoma incidence has been steadily increasing in recent years in most western countries, thus suggesting a role of environmental risk factors. Among these determinants, it has been hypothesized that some trace elements of nutritional and toxicological interest may be implicated in the etiology of the disease. We examined patients with newly diagnosed melanoma of the skin and population controls from the Modena province northern Italy. Clinical and dietary data were collected through questionnaires, and toenails were sampled for trace element determination. Levels of cadmium, chromium, lead, selenium, zinc, copper and iron in toenails were measured by inductively coupled plasma optical emission spectrometry and by neutron activation analysis. Data obtained from 58 cases and 58 controls indicated higher levels of copper and lower concentrations of iron in melanoma patients, whilst no other differences were seen for the remaining elements. Patterns of correlations of zinc and copper with the estimated intake of some dietary factors were different between cases and controls. Results of the present study suggest that abnormal intake or metabolism of copper and of iron might be implicated in the etiology of melanoma, whilst they do not indicate an involvement of exposure to cadmium, chromium, lead, selenium and zinc in this disease.

Case-Control Studies↗

PubMed2005

A population-based case-control study of diet and melanoma risk in northern Italy.

OBJECTIVE: We aimed at examining the association between dietary constituents and risk of cutaneous melanoma. DESIGN: In an area of northern Italy we recruited 59 newly diagnosed melanoma patients and 59 age- and sex-matched population controls, to whom we administered a validated semi-quantitative food-frequency questionnaire. RESULTS: We found an excess risk of melanoma in subjects with a higher energy-adjusted intake of total polyunsaturated fatty acids and, in particular, of linoleic acid (relative risk = 2.16 for intake in the highest tertile compared with the lowest tertile, P for linear trend = 0.061). Conversely, disease risk was inversely associated with the consumption of soluble carbohydrates (relative risk = 0.34 for intake in the upper vs. the lowest tertile adjusting for total energy intake, P for linear trend = 0.046). No other dietary factors, including alcohol, vitamins and trace elements, correlated with melanoma risk. The association of melanoma risk with linoleic acid and soluble carbohydrates intakes was further strengthened in multivariate analysis, and when analysis was limited to females. CONCLUSIONS: Overall, these results indicate that an excess energy-adjusted intake of linoleic acid and a lower consumption of soluble carbohydrates may increase melanoma risk.

Case-Control Studies↗

PubMed2005

Serum fructosamine and subsequent breast cancer risk: a nested case-control study in the ORDET prospective cohort study.

There is evidence that abnormal glucose metabolism may contribute to the risk of breast cancer. The measurement of markers of glucose metabolism could help to identify women at risk for breast cancer. Serum fructosamine is one such marker. In this study, we investigated whether prediagnostic serum fructosamine was associated with breast cancer. Between 1987 and 1992, 10,786 women ages 35 to 69 were recruited in Italy for a prospective study. Women with a history of cancer or on hormone therapy were excluded at baseline. Blood samples were collected after 12 hours fasting from all participants at recruitment. After 5.5 years of follow-up, 144 breast cancer cases were identified and four matched controls were selected from the cohort; serum fructosamine levels were measured in both groups at baseline. Adjusted odds ratios (OR) for the highest tertile of serum fructosamine compared to the lowest was 1.60 [95% confidence interval (CI), 0.95-2.73]. In premenopausal women, the OR was 1.58 (95% CI, 0.76-3.40) and in postmenopausal women, the OR was 1.60 (95% CI, 0.76-3.48). Serum fructosamine levels tended to be positively associated with breast cancer risk independent of menopausal status.

Adult↗

PubMed2004

Endogenous sex hormones and subsequent breast cancer in premenopausal women.

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80 degrees C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% CI = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.

Adult↗