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M Jenab,
S Salvini,
C H van Gils,
M Brustad,
S Shakya-Shrestha,
B Buijsse,
H Verhagen,
M Touvier, C Biessy,
P Wallström, [......],
R Travis,
M C Boutron-Ruault,
M Niravong,
H B Bueno-de-Mesquita,
Y T van der Schouw,
M J Tormo,
A Barricarte,
E Riboli,
S Bingham,
N Slimani
[show abstract]
[hide abstract]
ABSTRACT: To describe the intake of the fat-soluble nutrients retinol, beta-carotene, vitamin E and vitamin D and their food sources among 27 redefined centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Between 1995 and 2000, 36,034 subjects (age range: 35-74 years) completed a single standardized 24-h dietary recall using a computerized interview software program (EPIC-SOFT). Intakes of the fat-soluble nutrients were estimated using the standardized EPIC Nutrient Database.
For all the nutrients, in most centres, men had a higher level of intake than did women, even after adjustments for total energy intake and anthropometric confounders. Distinct regional gradients from northern to southern European countries were observed for all nutrients. The level intake of beta-carotene and vitamin E also showed some differences by level of education, smoking status and physical activity. No meaningful differences in the nutrient intake were observed by age range.
These results show differences by study centre, gender, age and various lifestyle variables in the intake of retinol, beta-carotene, vitamin E and vitamin D between 10 European countries.
European journal of clinical nutrition 11/2009; 63 Suppl 4:S150-78. · 3.07 Impact Factor
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P Ferrari,
A Roddam,
M T Fahey,
M Jenab,
C Bamia,
M Ocké,
P Amiano,
A Hjartåker, C Biessy,
S Rinaldi, [......],
C L Parr,
T Braaten,
M Dorronsoro,
T Berenguer,
B Gullberg,
I Johansson,
A A Welch,
E Riboli,
S Bingham,
N Slimani
[show abstract]
[hide abstract]
ABSTRACT: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, the performance of 24-h dietary recall (24-HDR) measurements as reference measurements in a linear regression calibration model is evaluated critically at the individual (within-centre) and aggregate (between-centre) levels by using unbiased estimates of urinary measurements of nitrogen and potassium intakes.
Between 1995 and 1999, 1072 study subjects (59% women) from 12 EPIC centres volunteered to collect 24-h urine samples. Log-transformed questionnaire, 24-HDR and urinary measurements of nitrogen and potassium intakes were analysed in a multivariate measurement error model to estimate the validity of coefficients and error correlations in self-reported dietary measurements. In parallel, correlations between means of 24-HDR and urinary measurements were computed. Linear regression calibration models were used to estimate the regression dilution (attenuation) factors.
After adjustment for sex, centre, age, body mass index and height, the validity coefficients for 24-HDRs were 0.285 (95% confidence interval: 0.194, 0.367) and 0.371 (0.291, 0.446) for nitrogen and potassium intakes, respectively. The attenuation factors estimated in a linear regression calibration model were 0.368 (0.228, 0.508) for nitrogen and 0.500 (0.361, 0.639) for potassium intakes; only the former was different from the estimate obtained using urinary measurements in the measurement error model. The aggregate-level correlation coefficients between means of urinary and 24-HDR measurements were 0.838 (0.637, 0.932) and 0.756 (0.481, 0.895) for nitrogen and potassium intakes, respectively.
This study suggests that 24-HDRs can be used as reference measurements at the individual and aggregate levels for potassium intake, whereas, for nitrogen intake, good performance is observed for between-centre calibration, but some limitations are apparent at the individual level.
European journal of clinical nutrition 11/2009; 63 Suppl 4:S179-87. · 3.07 Impact Factor
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M M E van Bakel,
R Kaaks,
E J M Feskens,
S Rohrmann,
A A Welch,
V Pala,
K Avloniti,
Y T van der Schouw,
D L van der A,
H Du, [......],
E Sonestedt,
I Johansson,
M Schulze,
E Ardanaz,
G Buckland,
A Tjønneland,
K Overvad,
S Bingham,
E Riboli,
N Slimani
[show abstract]
[hide abstract]
ABSTRACT: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics.
Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall.
GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries.
GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.
European journal of clinical nutrition 11/2009; 63 Suppl 4:S188-205. · 3.07 Impact Factor
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N Slimani,
G Deharveng,
D A T Southgate, C Biessy,
V Chajès,
M M E van Bakel,
M C Boutron-Ruault,
A McTaggart,
S Grioni,
J Verkaik-Kloosterman, [......],
M C Ocké,
Y T van der Schouw,
B Bendinelli,
C Lauria,
M Brustad,
A Hjartåker,
A Tjønneland,
A M Jensen,
E Riboli,
S Bingham
[show abstract]
[hide abstract]
ABSTRACT: To describe the contribution of highly processed foods to total diet, nutrient intakes and patterns among 27 redefined centres in the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Single 24-hour dietary recalls were collected from 36,034 individuals (aged 35-74 years) using a standardized computerized interview programme (EPIC-SOFT). Centre-specific mean food intakes (g/day) were computed according to their degree of food processing (that is, highly, moderately and non-processed foods) using a specifically designed classification system. The contribution (%) of highly processed foods to the centre mean intakes of diet and 26 nutrients (including energy) was estimated using a standardized nutrient database (ENDB). The effect of different possible confounders was also investigated.
Highly processed foods were an important source of the nutrients considered, contributing between 61% (Spain) and 78-79% (the Netherlands and Germany) of mean energy intakes. Only two nutrients, beta-carotene (34-46%) and vitamin C (28-36%), had a contribution from highly processed foods below 50% in Nordic countries, in Germany, the Netherlands and the United Kingdom, whereas for the other nutrients, the contribution varied from 50 to 91% (excluding alcohol). In southern countries (Greece, Spain, Italy and France), the overall contribution of highly processed foods to nutrient intakes was lower and consisted largely of staple or basic foods (for example, bread, pasta/rice, milk, vegetable oils), whereas highly processed foods such as crisp bread, breakfast cereals, margarine and other commercial foods contributed more in Nordic and central European centres.
Highly industrially processed foods dominate diets and nutrient patterns in Nordic and central European countries. The greater variations observed within southern countries may reflect both a larger contribution of non/moderately processed staple foods along with a move from traditional to more industrialized dietary patterns.
European journal of clinical nutrition 11/2009; 63 Suppl 4:S206-25. · 3.07 Impact Factor
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S Rinaldi,
P H M Peeters,
I D Bezemer,
L Dossus, C Biessy,
C Sacerdote,
F Berrino,
S Panico,
D Palli,
R Tumino, [......],
M Koliva,
G Kyriazi,
A Thrichopoulou,
M C Boutron-Ruault,
F Clavel-Chapelon,
P Ferrari,
N Slimani,
R Saracci,
E Riboli,
R Kaaks
[show abstract]
[hide abstract]
ABSTRACT: Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC).
Serum levels of testosterone (T), androstenedione (Delta4), dehydroepiandrosterone sulphate (DHEAS), estrone (E1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires.
Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta4, and E1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers.
This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood.
Cancer Causes and Control 11/2006; 17(8):1033-43. · 2.88 Impact Factor
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S Rinaldi,
P H M Peeters,
F Berrino,
L Dossus, C Biessy,
A Olsen,
A Tjonneland,
K Overvad,
F Clavel-Chapelon,
M C Boutron-Ruault, [......],
J R Quiros,
S Bingham,
K T Khaw,
T Key,
N E Allen,
A Lukanova,
N Slimani,
R Saracci,
E Riboli,
R Kaaks
[show abstract]
[hide abstract]
ABSTRACT: Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.
Endocrine Related Cancer 07/2006; 13(2):593-605. · 4.36 Impact Factor
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F Canzian,
J D McKay,
R J Cleveland,
L Dossus, C Biessy,
S Rinaldi,
S Landi,
C Boillot,
S Monnier,
V Chajès, [......],
N Larrañaga,
C Martínez-García,
N E Allen,
T J Key,
S A Bingham,
K-T Khaw,
N Slimani,
T Norat,
E Riboli,
R Kaaks
[show abstract]
[hide abstract]
ABSTRACT: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.
British Journal of Cancer 02/2006; 94(2):299-307. · 5.04 Impact Factor
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F Canzian,
J D McKay,
R J Cleveland,
L Dossus, C Biessy,
S Rinaldi,
S Landi,
C Boillot,
S Monnier,
V Chaj|[egrave]|s, [......],
N Larra|[ntilde]|aga,
C Mart|[iacute]|nez-Garc|[iacute]|a,
N E Allen,
T J Key,
S A Bingham,
K-T Khaw,
N Slimani,
T Norat,
E Riboli,
R Kaaks
[show abstract]
[hide abstract]
ABSTRACT: Material and methods Results Discussion References Acknowledgements Figures and TablesInsulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case–control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.Keywords: IGF-I, IGFBP-3, IGFBP-1, IGFALS, single nucleotide polymorphisms, breast cancer
British Journal of Cancer 01/2006; 94(2):299-307. · 5.04 Impact Factor
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R Kaaks,
S Rinaldi,
T J Key,
F Berrino,
P H M Peeters, C Biessy,
L Dossus,
A Lukanova,
S Bingham,
K-T Khaw, [......],
S Panico,
R Tumino,
P Vineis,
A Trichopoulou,
V Kalapothaki,
D Trichopoulos,
P Ferrari,
T Norat,
R Saracci,
E Riboli
[show abstract]
[hide abstract]
ABSTRACT: Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids -the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
Endocrine Related Cancer 01/2006; 12(4):1071-82. · 4.36 Impact Factor
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R Kaaks,
S Rinaldi,
T J Key,
F Berrino,
P H M Peeters, C Biessy,
L Dossus,
A Lukanova,
S Bingham,
K-T Khaw, [......],
S Panico,
R Tumino,
P Vineis,
A Trichopoulou,
V Kalapothaki,
D Trichopoulos,
P Ferrari,
T Norat,
R Saracci,
E Riboli
[show abstract]
[hide abstract]
ABSTRACT: Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (D4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids – the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk. Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
Endocrine Related Cancer 01/2005; 122813(12):1071-10826152. · 4.36 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To assess the effects of a comprehensive change in dietary composition on endogenous hormone metabolism. The specific aim was to examine whether this intervention could lead to favourable changes in insulin sensitivity, levels of IGF-I and IGF-binding proteins (IGFBPs), and total and bioavailable testosterone and estradiol, that would be expected to reduce breast cancer risk.
Randomised dietary intervention study; duration of 5 months.
From a total of 99 postmenopausal women, who had elevated baseline plasma testosterone levels, 49 women were randomly assigned to the dietary intervention arm and the other 50 to a control group.
Main aspects of the dietary intervention were reductions in the intake of total fat and refined carbohydrates, an increase in the ratio of n-3 over n-6 plus saturated fatty acids, and increased intakes of foods rich in dietary fibre and phytooestrogens.
Relative to the control group, women of the intervention group showed a significant reduction of body weight, waist circumference, fasting serum levels of testosterone, C peptide, glucose, and insulin area after glucose tolerance test, and a significant increase of serum levels of sex hormone-binding globulin, IGFBP-1, -2, and growth hormone-binding protein. Serum levels of IGF-I did not change.
This comprehensive dietary intervention strategy proved to be successful in inducing changes in endogenous hormone metabolism that might eventually result in reduced breast cancer risk. Additional studies are needed to show whether the dietary intervention and related hormonal changes can be both maintained over longer periods, of at least several years.
European Journal of Clinical Nutrition 10/2003; 57(9):1079-88. · 2.46 Impact Factor
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[show abstract]
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ABSTRACT: Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P<0.01), and a strong drop in the 5th quintile of BMI. However, levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I, with a significant increase in the second quintile of IGF-I compared with other levels. The absence of an association between plasma levels of androgens and prostate cancer risk in analytical studies, despite the strong indirect evidence of their tumour-stimulating effects, may reflect the complex and mostly inverse associations of androgenicity to IGF-I, insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer.
European Journal of Cancer Prevention 08/2003; 12(4):309-15. · 2.13 Impact Factor
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ABSTRACT: Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such large-scale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5-androstane-3, 17-diol (ADIOL), estrone (E1), estradiol (E2), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16-hydroxyestrone (16(OH)-E1) and the ratio of 2(OH)-E and 16(OH)-E1, in a representative sub-sample of post-menopausal women (n = 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E1 and E2 were measured by radio immunoassay after enzymatic hydrolysis, solid-phase extraction and HPLC purification of the samples, while 2(OH)-E and 16(OH)-E1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r = 0.85), acceptable for E2, E1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16(OH)-E1 and their ratio (r < 0.46).="" the="" adjustment="" for="" creatinine="" concentrations="" did="" not="" increase="" these="">
European Journal of Epidemiology 04/2003; 18(5):417-424. · 4.71 Impact Factor
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[show abstract]
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ABSTRACT: Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such large-scale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5alpha-androstane-3alpha, 17beta-diol (ADIOL), estrone (E1), estradiol (E2), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16alpha-hydroxyestrone (16alpha(OH)-E1) and the ratio of 2(OH)-E and 16alpha(OH)-E1, in a representative sub-sample of post-menopausal women (n = 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E1 and E2 were measured by radio immunoassay after enzymatic hydrolysis, solid-phase extraction and HPLC purification of the samples, while 2(OH)-E and 16alpha(OH)-E1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r = 0.85), acceptable for E2, E1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16alpha(OH)-E1 and their ratio (r < 0.46). The adjustment for creatinine concentrations did not increase these correlations.
European Journal of Epidemiology 01/2003; 18(5):417-24. · 4.71 Impact Factor
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ABSTRACT: Insulin-like growth factor 1 (IGF-1) has antiapoptotic and mitogenic effects on various cell types, and raised IGF-1 levels are increasingly being implicated as potential risk factors for cancer.
To examine the relationship between IGF-1 and its major plasma binding protein, IGF binding protein 3 (IGFBP-3), and the risk of colorectal cancer.
We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort. IGF-1 and IGFBP-3 were measured in prediagnostic plasma samples from 168 men and women who developed cancers of the colon (n=110) or rectum (n=58), and from 336 matched controls.
Conditional logistic regression analyses showed an increase in colon cancer risk with increasing levels of IGF-1 (odds ratios (ORs) 1.00, 1.89, 2.30, 2.66; p(trend)=0.03) and IGFBP-3 (ORs 1.00, 0.91, 1.80, 1.93; p(trend)=0.02). Rectal cancer risk was inversely related to levels of IGF-1 (ORs 1.00, 0.45, 0.33, 0.33; p(trend)=0.09) and IGFBP-3 (ORs 1.00, 0.75, 0.66, 0.49; p(trend)=0.21). Mutual adjustments between IGF-1 and IGFBP-3 did not materially alter these relationships.
These results support earlier findings of increased risk of colon cancer in subjects with elevated plasma IGF-1. Our results however do not support the hypothesis that the risk of rectal cancer could also be directly related to IGF-1 levels.
Gut 06/2002; 50(5):642-6. · 10.11 Impact Factor
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S Rinaldi,
H Déchaud, C Biessy,
V Morin-Raverot,
P Toniolo,
A Zeleniuch-Jacquotte,
A Akhmedkhanov,
R E Shore,
G Secreto,
A Ciampi,
E Riboli,
R Kaaks
[show abstract]
[hide abstract]
ABSTRACT: 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.
Cancer Epidemiology Biomarkers & Prevention 08/2001; 10(7):757-65. · 4.12 Impact Factor
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ABSTRACT: 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.
International Journal of Cancer 07/2001; 92(6):888-92. · 5.44 Impact Factor
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ABSTRACT: Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.
We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.
Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).
Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.
JNCI Journal of the National Cancer Institute 10/2000; 92(19):1592-600. · 13.76 Impact Factor
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F Canzian,
J.D. McKay,
R J Cleveland,
L. Dossus, C. Biessy,
C Boillot,
S Rinaldi,
M. Llewellyn,
V. Chajes,
F. Clavel-Chapelon, [......],
N. Larrangara,
C. Martinez-Garcia,
N.E. Allen,
T.J. Key,
S Bingham,
K T Khaw,
N. Slimani,
T. Norat,
E Riboli,
R. Kaaks
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F Canzian,
J.D. McKay,
R J Cleveland,
L. Dossus, C. Biessy,
S Rinaldi,
S Landi,
C Boillot,
S Monnier,
V. Chajes, [......],
N. Larranaga,
C. Martinez-Garcia,
N.E. Allen,
T.J. Key,
S Bingham,
K T Khaw,
N. Slimani,
T. Norat,
E Riboli,
R. Kaaks
