| 1. |
- Arslan, Alan A., et al.
(författare)
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Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women
- 2014
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:7, s. 1290-1297
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16 alpha-hydroxylation pathway may be inversely associated with breast cancer risk. Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and the 2-OHE1: 16 alpha-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16 alpha-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation. Results: Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16 alpha-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P <= 0.03). We observed a protective association of 2-OHE1 with ER + breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)]. Conclusions: In this study, higher levels of 2-OHE1 were associated with reduced risk of ER + breast cancer in postmenopausal women after adjustment for circulating estrone. Impact: These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.
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| 2. |
- Clendenen, Tess, et al.
(författare)
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Genetic variants in hormone-related genes and risk of breast cancer
- 2013
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Ingår i: PLOS ONE. - SAN FRANCISCO : PLoS, Public Library of Science. - 1932-6203. ; 8:7, s. e69367-
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.
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| 3. |
- Clendenen, Tess V., et al.
(författare)
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Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
- 2015
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Ingår i: PLOS ONE. - : PLOS one. - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
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| 4. |
- Lukanova, Annekatrin, et al.
(författare)
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Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:3, s. 425-432
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.
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| 5. |
- Lukanova, Annekatrin, et al.
(författare)
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Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:2, s. 262-268
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Tidskriftsartikel (refereegranskat)abstract
- Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
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| 6. |
- Lundin, Eva, et al.
(författare)
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Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer
- 2012
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:5, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (ORper allele = 1.22, 95% CI = 1.01-1.47, p(trend) = 0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (ORper allele = 1.20, 95% CI = 0.99-1.45, p(trend) = 0.06). PGR rs1042838 was also marginally associated with risk (ORper allele = 1.25, 95% CI = 0.96-1.61, p(trend) = 0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer. (C) 2012 Elsevier Ltd. All rights reserved.
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| 7. |
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| 8. |
- Scarmo, Stephanie, et al.
(författare)
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Circulating levels of 25-hydroxyvitamin D and risk of breast cancer : a nested case-control study
- 2013
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 15:1, s. R15-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH) D) in breast cancer development, but the results of epidemiological studies have been inconsistent.Methods: We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH) D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.Results: No association was observed between circulating levels of 25(OH) D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile, ptrend = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH) D > 0.70). An inverse association between 25(OH) D levels and breast cancer risk was observed among women who were = 45 years of age (ORQ5-Q1 = 0.48, 95% CI = 0.30-0.79, ptrend = 0.01) or premenopausal at enrollment (ORQ5-Q1 = 0.67, 95% CI = 0.48-0.92, ptrend = 0.03).Conclusions: Circulating 25(OH) D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention.
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| 9. |
- Zeleniuch-Jacquotte, Anne, et al.
(författare)
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Circulating enterolactone and risk of endometrial cancer
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:10, s. 2376-2381
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.
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