Hormone therapy, DNA methylation and colon cancer.

Observational epidemiological studies and randomized trials have reported a protective effect of estrogen and progestin therapy (EPT) on the risk of colorectal cancer but the findings on estrogen-alone therapy (ET) are less consistent. The mechanism by which menopausal hormones influence risk of colorectal cancer has not been well studied. To further investigate the relationship between menopausal hormones and risk of colon cancer, we conducted a population-based case-control study in Los Angeles County involving 831 women with newly diagnosed colon cancer and 755 population-based control women. Risk of colon cancer decreased significantly with increasing duration of current use of ET and EPT; the adjusted relative risk was 0.83 [95% confidence interval (95% CI) = 0.76-0.99)] per 5 years of ET use and 0.88 (95% CI = 0.78-0.99) per 5 years of EPT use. Risk of colon cancer was unrelated to past ET or EPT use. We explored if current use of menopausal hormones is associated with DNA methylation of estrogen receptor (ESR1 and ESR2), progesterone receptor and other genes in the colonic tissues of a subset of colon cancer patients (n = 280) we interviewed. Our results suggest that current menopausal hormone users compared with non-current users displayed increased DNA methylation of progesterone receptor in the 'normal' colonic tissues (P = 0.055) and increased DNA methylation of ESR1 in the 'tumorous' colonic tissues (P = 0.056). These findings on DNA methylation and hormone therapy use need confirmation in larger studies.

[1]  S. Gruber,et al.  Use of hormone replacement therapy and the risk of colorectal cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  R. Prentice,et al.  Colorectal Cancer in Relation to Postmenopausal Estrogen and Estrogen Plus Progestin in the Women's Health Initiative Clinical Trial and Observational Study , 2009, Cancer Epidemiology Biomarkers & Prevention.

[3]  R. Shore,et al.  Postmenopausal Levels of Endogenous Sex Hormones and Risk of Colorectal Cancer , 2009, Cancer Epidemiology Biomarkers & Prevention.

[4]  J. Thigpen.  Menopausal Hormone Therapy and Risk of Colorectal Cancer , 2009 .

[5]  J. Stanford,et al.  Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial , 2008, Cancer Epidemiology Biomarkers & Prevention.

[6]  D. Winter,et al.  Oestrogen and the colon: potential mechanisms for cancer prevention. , 2008, The Lancet. Oncology.

[7]  J. Manson,et al.  Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. , 2007, Cancer research.

[8]  C. la Vecchia,et al.  Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  A. Meikle.  Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy , 2008 .

[10]  M. Slattery,et al.  Changing population characteristics, effect-measure modification, and cancer risk factor identification , 2007, Epidemiologic perspectives & innovations : EP+I.

[11]  J. Potter,et al.  Estrogen plus progestin use, microsatellite instability, and the risk of colorectal cancer in women. , 2007, Cancer research.

[12]  Dawei Xie,et al.  A simulation using data from a primary care practice database closely replicated the women's health initiative trial. , 2007, Journal of clinical epidemiology.

[13]  P. Newcomb,et al.  Exogenous hormones and colorectal cancer risk in Canada: associations stratified by clinically defined familial risk of cancer , 2007, Cancer Causes & Control.

[14]  A. Assmann,et al.  Colon cancer risk and different HRT formulations: a case-control study , 2007, BMC Cancer.

[15]  D. Hunter,et al.  O6-Methylguanine-DNA Methyltransferase Leu84Phe and Ile143Val Polymorphisms and Risk of Colorectal Cancer in the Nurses’ Health Study and Physicians’ Health Study (United States) , 2006, Cancer Causes & Control.

[16]  P. Laird,et al.  DNA methylation profiles of female steroid hormone-driven human malignancies. , 2006, Current topics in microbiology and immunology.

[17]  Christian B. Woods,et al.  Analysis of repetitive element DNA methylation by MethyLight , 2005, Nucleic acids research.

[18]  Gary L Rosner,et al.  Tumour vasculature: On the verge of collapse , 2005, Nature Reviews Cancer.

[19]  P. Laird,et al.  Gene-Specific Methylation and Subsequent Risk of Colorectal Adenomas among Participants of the Polyp Prevention Trial , 2005, Cancer Epidemiology Biomarkers & Prevention.

[20]  Jian Yu,et al.  Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. , 2004, World Journal of Gastroenterology.

[21]  K. Machens,et al.  Estrogen plus progestin and colorectal cancer in postmenopausal women. , 2004, The New England journal of medicine.

[22]  Martin Widschwendter,et al.  Association of Breast Cancer DNA Methylation Profiles with Hormone Receptor Status and Response to Tamoxifen , 2004, Cancer Research.

[23]  John Robbins,et al.  National cross sectional survey to determine whether the decision to delivery interval is critical in emergency caesarean section , 2004, BMJ : British Medical Journal.

[24]  J. Hanley,et al.  The effects of transdermal and oral oestrogen replacement therapy on colorectal cancer risk in postmenopausal women , 2004, British Journal of Cancer.

[25]  Peter Nürnberg,et al.  Distinct methylation profiles of glioma subtypes , 2003, International journal of cancer.

[26]  R Alexandra Goldbohm,et al.  Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. , 2003, Cancer research.

[27]  P. Laird,et al.  MethyLight: a high-throughput assay to measure DNA methylation. , 2000, Nucleic acids research.

[28]  P. Laird,et al.  CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. , 1999, Cancer research.

[29]  F. Grodstein,et al.  Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis , 1999 .

[30]  Malcolm C. Pike,et al.  Estrogen-Progestin Replacement Therapy and Endometrial Cancer , 1997 .

[31]  J. Gustafsson,et al.  The novel estrogen receptor‐β subtype: potential role in the cell‐ and promoter‐specific actions of estrogens and anti‐estrogens , 1997, FEBS letters.

[32]  A. Olek,et al.  A modified and improved method for bisulphite based cytosine methylation analysis. , 1996, Nucleic acids research.

[33]  J. Gustafsson,et al.  Cloning of a novel receptor expressed in rat prostate and ovary. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  S. Baylin,et al.  Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon , 1994, Nature Genetics.

[35]  M. Pike,et al.  Re-evaluating the role of progestogen therapy after the menopause. , 1988, Fertility and sterility.

[36]  J. Potter,et al.  Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. , 1980, Journal of the National Cancer Institute.