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High follicular phase luteinizing hormone levels in young healthy BRCA1 mutation carriers: Implications for breast and ovarian cancer risk.

Jernström, Helena LU ; Borg, Åke LU and Olsson, Håkan LU (2005) In Molecular Genetics and Metabolism 86(1-2). p.320-327
Abstract
BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer and 20-40% risk of developing ovarian cancer. High LH levels have been linked to increased risks of both breast and ovarian cancers in some studies and it is unknown whether gonadotropin levels are associated with BRCA1 mutation status. The aim of the study was to explore whether gonadotropin levels were associated with BRCA1 mutation status among healthy <= 40-year-old-women from hereditary breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured height, weight, breast volumes, and plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5-10 and once again... (More)
BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer and 20-40% risk of developing ovarian cancer. High LH levels have been linked to increased risks of both breast and ovarian cancers in some studies and it is unknown whether gonadotropin levels are associated with BRCA1 mutation status. The aim of the study was to explore whether gonadotropin levels were associated with BRCA1 mutation status among healthy <= 40-year-old-women from hereditary breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured height, weight, breast volumes, and plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5-10 and once again during cycle days 18-23 in 43 non-carriers from BRCA1 families, 20 BRCA1 mutation carriers, and 101 women from non-BRCA1/2 families. The strongest predictors of high LH levels among BRCA1 mutation carriers and non-carriers during cycle days 5-10 were being a BRCA1 mutation carrier (p = 0.002), lack of current OC use (p = 0.003), and being nulliparous (p = 0.01), adjusted for age and menstrual cycle day when the samples were obtained. This association was seen both in non-OC users and current OC users but was only significant in the former group (p = 0.005). Because of multiple analyses it is possible that our finding is a result of a Type 1 statistical error. After a permutation test the new adjusted p value in non-OC users was 0.05. FSH and E2 were similar in non-carriers, BRCA1 mutation carriers and women from non-BRCA1/2 families. We found significantly elevated LH levels in the follicular phase among young healthy BRCA1 mutation carriers compared with non-carriers from BRCA1 families. This is a small study and confirmatory studies are warranted to establish whether elevated LH levels are part of the BRCA1 phenotype and may be manipulated in order to reduce cancer risks in BRCA1 mutation carriers. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FSH, oral, estradiol, breast cancer, BRCA1, ovarian cancer, LH, contraceptive use
in
Molecular Genetics and Metabolism
volume
86
issue
1-2
pages
320 - 327
publisher
Elsevier
external identifiers
  • wos:000232705900039
  • scopus:26244440241
ISSN
1096-7192
DOI
10.1016/j.ymgme.2005.06.007
language
English
LU publication?
yes
id
adcfbf3b-10a8-4359-a4e0-d405b165adad (old id 142932)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16084122&dopt=Abstract
date added to LUP
2007-07-23 11:58:32
date last changed
2017-01-01 05:02:40
@article{adcfbf3b-10a8-4359-a4e0-d405b165adad,
  abstract     = {BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer and 20-40% risk of developing ovarian cancer. High LH levels have been linked to increased risks of both breast and ovarian cancers in some studies and it is unknown whether gonadotropin levels are associated with BRCA1 mutation status. The aim of the study was to explore whether gonadotropin levels were associated with BRCA1 mutation status among healthy &lt;= 40-year-old-women from hereditary breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured height, weight, breast volumes, and plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5-10 and once again during cycle days 18-23 in 43 non-carriers from BRCA1 families, 20 BRCA1 mutation carriers, and 101 women from non-BRCA1/2 families. The strongest predictors of high LH levels among BRCA1 mutation carriers and non-carriers during cycle days 5-10 were being a BRCA1 mutation carrier (p = 0.002), lack of current OC use (p = 0.003), and being nulliparous (p = 0.01), adjusted for age and menstrual cycle day when the samples were obtained. This association was seen both in non-OC users and current OC users but was only significant in the former group (p = 0.005). Because of multiple analyses it is possible that our finding is a result of a Type 1 statistical error. After a permutation test the new adjusted p value in non-OC users was 0.05. FSH and E2 were similar in non-carriers, BRCA1 mutation carriers and women from non-BRCA1/2 families. We found significantly elevated LH levels in the follicular phase among young healthy BRCA1 mutation carriers compared with non-carriers from BRCA1 families. This is a small study and confirmatory studies are warranted to establish whether elevated LH levels are part of the BRCA1 phenotype and may be manipulated in order to reduce cancer risks in BRCA1 mutation carriers.},
  author       = {Jernström, Helena and Borg, Åke and Olsson, Håkan},
  issn         = {1096-7192},
  keyword      = {FSH,oral,estradiol,breast cancer,BRCA1,ovarian cancer,LH,contraceptive use},
  language     = {eng},
  number       = {1-2},
  pages        = {320--327},
  publisher    = {Elsevier},
  series       = {Molecular Genetics and Metabolism},
  title        = {High follicular phase luteinizing hormone levels in young healthy BRCA1 mutation carriers: Implications for breast and ovarian cancer risk.},
  url          = {http://dx.doi.org/10.1016/j.ymgme.2005.06.007},
  volume       = {86},
  year         = {2005},
}