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Genetic polymorphisms in breast cancer in relation to risk and prognosis

Bågeman, Erika LU (2008) In Lund University Faculty of Medicine Doctoral Dissertation Series 2008:86.
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... (More)
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. (Less)
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author
supervisor
opponent
  • Professor Hall, Per, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
age at diagnosis, breast cancer, polymorphism, CYP1A2, IGF1, GSTM1, CYP2C9, CYP2C8, coffee, GSTT1, ER, parity
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2008:86
pages
138 pages
publisher
Department of Oncology, Clinical Sciences, Lund University
defense location
Segerfalk Lecture Hall, Wallenberg Neuroscience Center, Lund
defense date
2008-10-23 13:00
ISSN
1652-8220
ISBN
978-91-86059-39-2
language
English
LU publication?
yes
id
2410b827-cd88-4341-81cb-f954c6120eea (old id 1242291)
date added to LUP
2008-10-01 08:36:40
date last changed
2016-09-19 08:44:51
@phdthesis{2410b827-cd88-4341-81cb-f954c6120eea,
  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<br/><br>
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.},
  author       = {Bågeman, Erika},
  isbn         = {978-91-86059-39-2},
  issn         = {1652-8220},
  keyword      = {age at diagnosis,breast cancer,polymorphism,CYP1A2,IGF1,GSTM1,CYP2C9,CYP2C8,coffee,GSTT1,ER,parity},
  language     = {eng},
  pages        = {138},
  publisher    = {Department of Oncology, Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University Faculty of Medicine Doctoral Dissertation Series},
  title        = {Genetic polymorphisms in breast cancer in relation to risk and prognosis},
  volume       = {2008:86},
  year         = {2008},
}