| 1. |
- Bågeman, Erika, et al.
(författare)
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Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women.
- 2007
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 96, s. 712-717
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Tidskriftsartikel (refereegranskat)abstract
- Multiparity decreases the risk of breast cancer in white women, whereas it is a risk factor in black women < 50 years. Early-onset breast cancer (< 50 years) has been associated with high insulin-like growth factor-I (IGF-I) levels. Absence of the common IGFI 19 cytosine-adenine ( CA)- repeat allele (IGFI-19/-19) inverts the effect of several non-genetic factors on breast cancer risk but the interaction between IGFI-19/-19 and multiparity on breast cancer risk is unknown. As IGFI-19/-19, multiparity and early-onset breast cancer are more common in black than in white women, we aimed to study whether multiparity combined with IGFI-19/-19 increases the risk of early-onset breast cancer. Four hundred and three breast cancer patients diagnosed in Lund, Sweden, at age 25 - 99 years were genotyped for the IGFI CA-repeat length using fragment analysis. Overall, 12.9% carried the IGFI-19/-19 genotype. There was a highly significant interaction between multiparity and IGFI-19/-19 on age at breast cancer diagnosis ( P = 0.007). Among IGFI-19/-19 patients, multiparity was associated with a 9.2 year earlier age at diagnosis compared with uniparity or nulliparity ( P = 0.006). Multiparity combined with IGFI-19/-19 was associated with an early age at breast cancer diagnosis. If confirmed, IGFI-19/-19 may help identify a subgroup of women for earlier breast cancer screening.
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| 2. |
- Bågeman, Erika, et al.
(författare)
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Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status.
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 17:4, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16alpha-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16alpha-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (>/=2 cups per day) combined with the CYP1A2*1F A/A genotype would be associated with a later age at diagnosis and a greater proportion of ER-negative (ER-) tumors among patients with breast cancer. We genotyped 458 patients with breast cancer (age, 25-99 years) in Lund, Sweden, for CYP1A2*1F. Information on lifestyle factors and tumor characteristics were obtained from preoperative questionnaires and pathology reports. Among patients with CYP1A2*1F A/A (51.3%), moderate to high consumption was associated with a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, P = 0.0004). These patients were also more likely to have ER- tumors than patients with low consumption (14.7% versus 0%, P = 0.018). Coffee was not associated with ER status or age at diagnosis in patients with at least one C allele. Age at diagnosis was not associated with ER status in patients with CYP1A2*1F A/A, but younger patients (<50 years) with at least one C allele were more likely to have ER- tumors compared with older patients (odds ratio, 4.2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed.
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| 3. |
- Bågeman, Erika
(författare)
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Genetic polymorphisms in breast cancer in relation to risk and prognosis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common cancer in women living in Sweden and the second most common cancer in the rest of the world. The risk of developing breast cancer is modified by environment, lifestyle, genetics and a combination of these factors. In this thesis work the combination of lifestyle and genetic polymorphisms on tumor characteristics and early recurrence have been studied. Absence of the common 19 CA repeat allele in the insulin-like growth factor 1 gene (IGF1-19/-19) has been shown to modify the effect of several breast cancer risk factors. In Study I multiparous patients with IGF1-19/-19 were 5.9 years younger at diagnosis than all other patients (P=0.007). Women with this combination may thus benefit from earlier breast cancer screening. In Study II concomitant tamoxifen and radiation therapy, increasing alcohol intake and moderate to high coffee consumption were all associated with an increased 2-hydroxyestrogen (2-OHE) to 16α-hydroxyestrone (16αOHE1) ratio between the pre- and post-operative samples from the same patients. CYP1A2*1F C were correlated with a lower ratio at both the pre-and the post-operative visit. Since a high 2-OHE/16αOHE1 ratio has been associated with improved survival the identified factors may modify breast cancer prognosis. In Study III the combined effect of CYP1A2*1F and coffee consumption was evaluated in relation to age at diagnosis and estrogen receptor (ER) status. In patients with CYP1A2*1F A/A who had never used hormone replacement therapy, higher coffee consumption was associated with a later age at diagnosis (57.7 versus 48.0 years; P=0.001) than in patients with lower consumption. Higher coffee consumption was also associated with a higher proportion of ER negative tumors (14.7% versus 0%, P=0.018). In Study IV the frequencies of CYP2C8*3, CYP2C8*4, CYP2C9*2, CYP2C9*3, GSTM1*0 and GSTT1*0 were evaluated and haplotype blocks constructed. CYP2C8/9 *1/*4/*1/*1 was associated with a lower frequency of axillary lymph node involvement as compared with the wild type in tumors larger than 20 mm, OR 0.13 (95% CI 0.04-0.45; P=0.001). CYP2C8*3 was associated with an increased risk of early recurrence, especially in women who had received tamoxifen, HR 2.93 (95% CI 1.25-6.85; P=0.013). In conclusion, both genetic and lifestyle factors are important for breast cancer.
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| 4. |
- Henningson, Maria, et al.
(författare)
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Absence of the common IGF1 19 CA-repeat allele is more common among BRCA1 mutation carriers than among non-carriers from BRCA1 families.
- 2007
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:4, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 mutations predispose to early-onset breast cancer. We previously reported an association between absence of the common IGF1 19 CA-repeat allele (IGF1-19/-19) and being a BRCA1 mutation carrier in young women from breast cancer high-risk families. Others have reported a four-fold risk of premenopausal breast cancer in women with a family history and the IGF1-19/-19 genotype. The aim of this study was to investigate whether the IGF1-19/-19 genotype was associated with being a BRCA1 mutation carrier among women from BRCA1 families. DNA was available from 268 women with known BRCA1 status from the South Swedish Health Care Region. IGF1 genotyping was successfully performed with fragment analysis in 211 women from 96 families. The IGF1-19/-19 genotype was significantly more common among BRCA1 mutation carriers (14.2%) than among non-carriers (4.8%), OR 3.3 (95%CI 1.11-9.78, P = 0.03) adjusted for family clustering. We confirmed our previous finding of an association between the IGF1-19/-19 genotype and BRCA1 mutation status. Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.
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| 5. |
- Henningson, Maria, et al.
(författare)
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Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.
- 2010
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; Dec, s. 432-437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1 deletions, and GSTP1*1B and current oral contraceptive (OC) status. DESIGN: Questionnaires on reproductive factors and OC use were completed and blood samples were obtained during menstrual cycle day 18-23 in healthy women (≤40years) from breast cancer high-risk families. IGF-1 was analyzed with radioimmunoassay. Genetic analyses were done with PCR based methods. Initially 258 women were included. After exclusion 229 women were finally included in the analyses of IGF-1 in relation to GSTM1 and GSTT1. RESULTS: Among the 142 non-OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels (P(interaction)=0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had lower IGF-1 levels (P(interaction)=0.010). Among all 229 women, a three-way interaction model showed an interaction between the GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P(interaction)=0.003). GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was associated with early growth (P=0.003). CONCLUSION: Both OC use and GSTT1 and GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to confirm our finding and elucidate the clinical importance.
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| 6. |
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| 7. |
- Jernström, Helena, et al.
(författare)
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CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients
- 2009
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 101:11, s. 1817-1823
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Tidskriftsartikel (refereegranskat)abstract
- CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. Methods: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. Results: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11–5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53–51.1). Conclusion: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients.
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| 8. |
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| 9. |
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| 10. |
- Klug, T. L., et al.
(författare)
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Moderate coffee and alcohol consumption improves the estrogen metabolite profile in adjuvant treated breast cancer patients: A pilot study comparing pre- and post-operative levels
- 2006
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 89:4, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Most, but not all, studies have found that women with a high urinary 2-hydroxyestrogen (2OHE) to 16 alpha-hydroxyestrone (16 alpha OHE1) ratio are at reduced risk for breast cancer and have a better prognosis. The aim was to identify factors associated with the pre-operative 2OHE to 16 alpha OHE1 ratio and factors that predicted the change in the ratio between the pre-operative visit and first follow-up visit three to six months post-o.peratively among 59 women with primary ER positive breast cancer tumors. Body measurements, questionnaires and blood samples for measurements of the 2OHE and 16 alpha OHE1 plasma levels and CYP1A2*1F genotyping were collected at both visits. Post-operatively, 15 women received tamoxifen, 30 women tamoxifen and radiotherapy concomitantly, and 14 women radiotherapy. The pre-operative ratio was not correlated with tumor characteristics, but was significantly higher in women who consumed three or more cups of coffee daily (p = 0.009). The number of CYP1A2*1F Galleles was correlated with a lower ratio at both visits (p = 0.13 and p = 0.02, respectively). The ratio increased between the two visits in 69.5% of the women, The factors associated with a significant increase in the ratio were concomitant tamoxifen and radiotherapy (p = 0.006), increasing alcohol consumption (p = 0.006), and a high coffee consumption (p = 0.03), but not age or CYP1A2*1F genotype. In this pilot study, breast cancer patients who started tarnoxifen during radiotherapy and who had a moderate coffee and alcohol consumption demonstrated a significant improvement in their estrogen metabolite profile between the pre- and post-operative visits. (c) 2006 Elsevier Inc. All rights reserved.
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