| 1. |
- Bradlow, HL, et al.
(författare)
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Comparison of plasma and urinary levels of 2-hydroxyestrogen and 16 alpha-hydroxyestrogen metabolites
- 2006
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 87:2, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- A modified ELISA assay for measurement of the two estrogen metabolites 2-hydroxyestrone (2OHE1) and 16 alpha-hydroxyestrone (16 alpha OHE1) in plasma and serum has been developed. Previously, these have only been measured in urine. It is not known how well the measurements of these metabolites in urine and plasma are correlated. The goal of this study was to compare urinary and plasma levels of 2OHE1 and 16 alpha OHE1 and their ratios and to explore how they were affected by ethnicity, dietary and genetic factors, and medication use. Blood and urine samples were obtained from 511 nulliparous women, aged 17-35, from four ethnic groups during the same visit at the study center, on a random day of the menstrual cycle. The overall correlation between the 2OHE1/16 alpha OHE1 ratio in plasma and urine was fair (r(s) = 0.52; p < 0.0001). In general, the correlation between the 2OHE1/16 alpha OHE1 ratio in urine and plasma was higher among women not using oral contraceptives (OCs) (r(s) = 0.58; p < 0.0001) than among women currently using OCs (r(s) = 0.34; p < 0.0001). The correlation was highest for samples obtained during the mid-cycle in among non-OC users (r(s) = 0.83; p < 0.0001). Among non-OC users, the urinary 2OHE1/160 alpha OHE1 ratio was stable over the menstrual cycle while there was an increase in the plasma 2OHE1/16 alpha OHE1 ratio. The strongest factors predicting discordance between the urinary and plasma 2OHE1/16 alpha OHE1 ratios among non-OC users were a baseline urinary 20HE1/16 alpha OHE1 ratio in the three upper quartiles (p < 0.001), the menstrual cycle phase (p = 0.001), and the number of cups of coffee consumed per day (p = 0.006). Among current OC users, the strongest predictors of discordance between the urinary and plasma 2OHE1/16 alpha OHE1 ratios were a baseline urinary 2IHE1/16 alpha OHE1 ratio in the three lower quartiles (p < 0.001), being black (p = 0.001), and being Asian (p = 0.014). In conclusion, we found that the correlation between the two methods was fair and varied according to the baseline urinary 2OHE1/16 alpha OHE1 ratio, ethnic group, OC status, coffee consumption, and time of menstrual cycle when the samples were obtained. (C) 2005 Elsevier Inc. All rights reserved.
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| 2. |
- Cullinane, CA, et al.
(författare)
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Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 117:6, s. 988-991
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Tidskriftsartikel (refereegranskat)abstract
- Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.
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| 3. |
- Gronwald, J, et al.
(författare)
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Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:9, s. 2281-2284
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Tidskriftsartikel (refereegranskat)abstract
- Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of similar to 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is similar to 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.304.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95% CI, 0.242.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65). (c) 2005 Wiley-Liss, Inc.
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