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- Kaaks, Rudolf, et al.
(författare)
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Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in Northern and Southern Sweden
- 2002
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Ingår i: Cancer Causes and Control. - 1573-7225 .- 0957-5243. ; 13:4, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. Methods: Within two prospective cohorts in Umea and Malmo we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. Results: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umea cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; p(trend) = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. Conclusions: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-1 and IGFBP-2, are associated with increased breast cancer risk.
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| 2. |
- Lukanova, Annekatrin, et al.
(författare)
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Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden).
- 2002
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Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 13:6, s. 509-516
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In this study we test the hypothesis of a nonlinear relationship of IGF-I with indices of body fat such as body mass index (BMI), insulin, and leptin.METHODS: The controls used in three case-control cancer studies nested in the Northern Sweden Health and Disease Cohort, were combined for this analysis. Measurements of plasma IGF-I, IGFBP-3, insulin, and leptin were available for 445 men and 391 women.RESULTS: In both men and women we found the highest mean IGF-I levels in subjects with BMI between 24 and 26. IGF-I concentrations decreased toward BMI < or = 20 and BMI > 30 in men; however, the results for women did not reach statistical significance. The molar ratio of IGF-I/IGFBP-3 showed a similar profile to that of IGF-I, although much less pronounced. The observed peak mean IGF-I levels in the second quintiles of insulin and leptin in men supported these findings. No significant variation of mean IGF-I levels across quintiles of insulin and leptin were observed in women.CONCLUSIONS: The results of this study provide evidence that IGF-I plasma concentrations vary substantially over a wide range of body weight and that the relationship is nonlinear.
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| 3. |
- Stattin, Pär, et al.
(författare)
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Plasma leptin and colorectal cancer risk : a prospective study in Northern Sweden.
- 2003
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 10:6, s. 2015-2021
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with an increased risk of colorectal cancer. Circulating levels of leptin are high in obesity and strongly correlated to levels of insulin. Leptin stimulates growth of colon cancer cells. In a nested case-control study, we measured leptin levels in prediagnostic plasma from 75 men and 93 women who were diagnosed with colorectal cancer mean time 3.4 years (SD 2.4) after recruitment and among 327 control subjects. Logistic regression analyses showed increases in colorectal cancer risk in men with increasing levels of leptin, odds ratios (OR) were 1.00 (ref), 0.85 (95% C.I.=0.33-2.23), 1.04 (0.43-2.53), and 2.15 (0.89-5.22), (pfor trend=0.08). There was a distinct threshold between the third and fourth quartile of leptin, and the odds ratio for top quartile vs. three bottom quartiles was 2.28 (1.09-4.76). Adjustment for body mass index and insulin did not affect risk estimates. In separate analysis, odds ratio for top vs. bottom tertile of colon cancer was 1.96 (95% C.I.=0.72-5.29), whereas no increase was seen for rectal cancer. In women, no association between leptin and risk was seen. These data support the hypothesis that leptin is a risk marker for colorectal cancer in men, but not in women.
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| 5. |
- Bianchini, Franca, et al.
(författare)
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Inverse correlation between alcohol consumption and lymphocyte levels of 8-hydroxydeoxyguanosine in humans
- 2001
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Ingår i: Carcinogenesis. - 0143-3334. ; 22:6, s. 885-890
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Tidskriftsartikel (refereegranskat)abstract
- In a cross-sectional study of 115 premenopausal non-smoking women, we examined the relationship between lymphocyte levels of 8-hydroxy-2'-deoxyguanosine (8-oxodGuo) and habitual alcohol consumption. The study was conducted in four different regions of Europe, including Potsdam (Germany), Turin (Italy), Malmo (Sweden) and Granada (Spain). Mean 8-oxodGuo levels differed significantly across study centres (P = 0.001), with the highest levels in Granada [2.17 8-oxodGuox10(-6) 2'-deoxyguanosine (95% confidence interval 1.27-4.40)] and lowest levels in Turin [1.19 (0.36-4.29)]. Mean levels of total alcohol intake and of types of alcoholic beverages consumed (wine, fortified wines, beer and cider) also differed across the study centres (P < 0.05), with the highest total alcohol consumption in Turin, and the lowest intake in GRANADA: When combining all the data, but adjusting for study centre, individual 8-oxodGuo level correlated inversely with alcohol intake. This inverse association remained unaltered after further adjustment for Quetelet Index, fruit and vegetable consumption, and plasma carotenoid levels. Furthermore, the inverse association was also observed for each of the study centres separately, and for different beverage types, with the exception of Granada, where the majority of women were non-drinkers and where alcohol intakes were also very low for the consumers. Finally, on a group level, mean levels of 8-oxodGuo and alcohol intake were also inversely associated between the four study centres. The finding of a relationship between alcohol consumption and 8-oxodGuo in lymphocytes was unexpected and not based on a prior hypothesis. This finding consequently requires confirmation from a randomized intervention study.
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| 10. |
- Lukanova, Annekatrin, 1966-
(författare)
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Endogenous hormones in the etiology of ovarian and endometrial cancers
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this thesis was to examine the relationship of pre-diagnostic circulating levels of sex-steroids (androgens and estrogens), sex hormone binding globuline (SHBG), insulin-like growth factor-I (IGF-I), IGF binding proteins (BP) and C-peptide (as a marker of pancreatic insulin secretion) with risk of ovarian and endometrial cancer. Additionally, the interrelationships of body mass index (BMI), sex-steroids, IGF-I and IGFBP-3 were examined. Two case-control studies were nested within 3 prospective cohort studies centered in New York (USA), Umeå (Sweden) and Milan (Italy). The ovarian study included 132 cancer cases. The endometrial study included 166 cancer cases in the IGF-I and C-peptide component and 124 postmenopausal cases in the sex-steroids component. For each case, two controls matching the case for cohort, age, menopausal status and date at recruitment were selected. In total 286 and 315 controls were included in the ovarian and endometrial cancer studies, respectively. Odds ratios (OR) and their 95% confidence intervals (CI) for cancer risk associated with increasing hormone concentrations were estimated by conditional logistic regression. The cross-sectional analysis was based on anthropometric and hormonal data from 620 controls selected for the two nested case-control studies. There was no association of prediagnostic androstenedione, testosterone, DHEAS, SHBG or estrone with ovarian cancer risk in the whole study population or in women who were pre- or postmenopausal at blood donation. In the premenopausal group, risk appeared to increase with increasing androstenedione (OR (95% CI) for the highest tertile: 2.35 (0.81-6.82), p=0.12). There was no association of IGF-I, IGFBP-1, 2, 3 or C-peptide concentrations with risk of ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at an early age (<55), circulating IGF-I was directly and strongly associated with risk (OR (95% CI): 4.74 (1.20-18.7), p<0.05 for the highest IGF-I tertile). In the endometrial study, previous observations were confimed that elevated circulating estrogens and androgens and decreased SHBG increase risk of developing endometrial malignancy after menopause. Multivariate ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels were: 4.13 (1.76-9.72), p<0.001 for estradiol; 3.67 (1.71-7.88), p=0.001 for estrone; 2.15 (1.05-4.40), p<0.04 for androstenedione; 1.74 (0.88-3.46), p=0.06 for testosterone; 2.90 (1.42-5.90), p<0.01 for DHEAS and 0.46 (0.20-1.05), p<0.01 for SHBG. Prediagnostic IGF-I, IGFBP-1, -2 and –3 were not related to risk of endometrial cancer in the whole study population. In postmenopausal women, levels of IGFBP-1 were inversely related to risk with an OR for the highest quartile of 0.36 (0.13-0.95), p<0.05. Endometrial cancer risk increased with increasing levels of C-peptide (p<0.01), up to an OR of 4.40 (1.65-11.7) for the highest quintile after adjustment for BMI and other confounders. The cross-sectional analyses showed that in both pre- and postmenopausal women SHBG decreased with increasing BMI. In the postmenopausal group, estrogens, testosterone and androstenedione increased with BMI, while the association with IGF-I was non-linear, the highest mean IGF-I concentration being observed in women with BMI between 24 and 25. In postmenopausal women, IGF-I was positively related to androgens, inversely correlated with SHBG, and was not correlated with estrogens. In conclusion, elevated pre-diagnostic sex-steroids, IGF-I or C-peptide increase risk of developing ovarian and endometrial cancer. BMI influences the circulating levels of these hormones, especially after menopause.
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