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Associations of hormone replacement therapy and oral contraceptives with risk of colorectal cancer defined by clinicopathological factors, beta-catenin alterations, expression of cyclin D1, p53, and microsatellite-instability

Brändstedt, Jenny LU ; Wangefjord, Sakarias LU ; Nodin, Björn LU ; Eberhard, Jakob LU ; Jirström, Karin LU and Manjer, Jonas LU (2014) In BMC Cancer 14(1). p.371-371
Abstract

BACKGROUND: Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.

METHOD: In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and... (More)

BACKGROUND: Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.

METHOD: In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never use among all women in the cohort. A multivariate Cox regression model was applied to determine hazard ratios for risk of CRC, overall and according to molecular subgroups, in relation to HRT and OC use.

RESULTS: There was no significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T-stage 1-2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09-0.77).Analysis stratified by tumour location revealed a reduced overall risk of rectal, but not colon, cancer among CHRT and ERT users, including T stage 1-2, lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative tumours.In unadjusted analysis, OC use was significantly associated with a reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar risk reduction was seen for the majority of clinicopathological and molecular subgroups.

CONCLUSION: Our findings provide information on the relationship between use of HRT and OC and risk of clinicopathological and molecular subsets of CRC.

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keywords
Biomarkers, Tumor, Colorectal Neoplasms, Contraceptives, Oral, Hormonal, Cyclin D1, Estrogen Replacement Therapy, Female, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Microsatellite Instability, Middle Aged, Multivariate Analysis, Neoplasm Staging, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sweden, Time Factors, Tissue Array Analysis, Tumor Suppressor Protein p53, beta Catenin, Journal Article, Research Support, Non-U.S. Gov't
in
BMC Cancer
volume
14
issue
1
pages
371 - 371
publisher
BioMed Central
external identifiers
  • pmid:24885829
  • wos:000336816700001
  • scopus:84901917862
ISSN
1471-2407
DOI
10.1186/1471-2407-14-371http://dx.doi.org/10.1186/1471-2407-14-371
language
English
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yes
id
775db729-79f3-45e1-8a1f-a6b482a0ce4a (old id 4529510)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24885829?dopt=Abstract
date added to LUP
2014-07-04 12:29:41
date last changed
2017-08-06 03:57:32
@article{775db729-79f3-45e1-8a1f-a6b482a0ce4a,
  abstract     = {<p>BACKGROUND: Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.</p><p>METHOD: In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never use among all women in the cohort. A multivariate Cox regression model was applied to determine hazard ratios for risk of CRC, overall and according to molecular subgroups, in relation to HRT and OC use.</p><p>RESULTS: There was no significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T-stage 1-2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09-0.77).Analysis stratified by tumour location revealed a reduced overall risk of rectal, but not colon, cancer among CHRT and ERT users, including T stage 1-2, lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative tumours.In unadjusted analysis, OC use was significantly associated with a reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar risk reduction was seen for the majority of clinicopathological and molecular subgroups.</p><p>CONCLUSION: Our findings provide information on the relationship between use of HRT and OC and risk of clinicopathological and molecular subsets of CRC.</p>},
  articleno    = {371},
  author       = {Brändstedt, Jenny and Wangefjord, Sakarias and Nodin, Björn and Eberhard, Jakob and Jirström, Karin and Manjer, Jonas},
  issn         = {1471-2407},
  keyword      = {Biomarkers, Tumor,Colorectal Neoplasms,Contraceptives, Oral, Hormonal,Cyclin D1,Estrogen Replacement Therapy,Female,Genetic Predisposition to Disease,Humans,Immunohistochemistry,Microsatellite Instability,Middle Aged,Multivariate Analysis,Neoplasm Staging,Proportional Hazards Models,Prospective Studies,Risk Assessment,Risk Factors,Sweden,Time Factors,Tissue Array Analysis,Tumor Suppressor Protein p53,beta Catenin,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {1},
  pages        = {371--371},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Associations of hormone replacement therapy and oral contraceptives with risk of colorectal cancer defined by clinicopathological factors, beta-catenin alterations, expression of cyclin D1, p53, and microsatellite-instability},
  url          = {http://dx.doi.org/10.1186/1471-2407-14-371http://dx.doi.org/10.1186/1471-2407-14-371},
  volume       = {14},
  year         = {2014},
}