Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer

Chi Chen Hong, Henry J. Thompson, Cheng Jiang, Geoffrey L. Hammond, David Tritchler, Martin Yaffe, Norman F. Boyd

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL→MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/detoxification of catecholestrogens. Subjects were recruited across five categories of breast density. Risk factor information, anthropometric measures, and blood samples were obtained; sex hormone and growth factor levels were measured, and COMT genotypes determined. Mammograms were digitized and measured using a computer-assisted method. After adjustment for age and ethnicity, among pre- but not postmenopausal subjects, each low-activity COMT*2 allele was associated with lower levels of percentage breast density. The statistical significance of this association was lost after further adjustment for serum growth factors [growth hormone, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3)], hormones [follicle-stimulating hormone (FSH) and progesterone], and body size (body mass index and waist:hip ratio). The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.

Original languageEnglish (US)
Pages (from-to)838-847
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume12
Issue number9
StatePublished - Sep 1 2003

Fingerprint

Catechol O-Methyltransferase
Breast Neoplasms
Follicle Stimulating Hormone
Alleles
Insulin-Like Growth Factor Binding Protein 3
Waist-Hip Ratio
Genes
Genotype
Gonadal Steroid Hormones
Body Size
Somatomedins
Progesterone
Intercellular Signaling Peptides and Proteins
Body Mass Index
Catechol Estrogens
Sex Factors
Serum
Growth Hormone
Cross-Sectional Studies
Breast Density

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Hong, C. C., Thompson, H. J., Jiang, C., Hammond, G. L., Tritchler, D., Yaffe, M., & Boyd, N. F. (2003). Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer. Cancer Epidemiology Biomarkers and Prevention, 12(9), 838-847.
Hong, Chi Chen ; Thompson, Henry J. ; Jiang, Cheng ; Hammond, Geoffrey L. ; Tritchler, David ; Yaffe, Martin ; Boyd, Norman F. / Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2003 ; Vol. 12, No. 9. pp. 838-847.
@article{581d9cc793474ac184c5d1286f6666d5,
title = "Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer",
abstract = "Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL→MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/detoxification of catecholestrogens. Subjects were recruited across five categories of breast density. Risk factor information, anthropometric measures, and blood samples were obtained; sex hormone and growth factor levels were measured, and COMT genotypes determined. Mammograms were digitized and measured using a computer-assisted method. After adjustment for age and ethnicity, among pre- but not postmenopausal subjects, each low-activity COMT*2 allele was associated with lower levels of percentage breast density. The statistical significance of this association was lost after further adjustment for serum growth factors [growth hormone, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3)], hormones [follicle-stimulating hormone (FSH) and progesterone], and body size (body mass index and waist:hip ratio). The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.",
author = "Hong, {Chi Chen} and Thompson, {Henry J.} and Cheng Jiang and Hammond, {Geoffrey L.} and David Tritchler and Martin Yaffe and Boyd, {Norman F.}",
year = "2003",
month = "9",
day = "1",
language = "English (US)",
volume = "12",
pages = "838--847",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

Hong, CC, Thompson, HJ, Jiang, C, Hammond, GL, Tritchler, D, Yaffe, M & Boyd, NF 2003, 'Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 12, no. 9, pp. 838-847.

Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer. / Hong, Chi Chen; Thompson, Henry J.; Jiang, Cheng; Hammond, Geoffrey L.; Tritchler, David; Yaffe, Martin; Boyd, Norman F.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 12, No. 9, 01.09.2003, p. 838-847.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer

AU - Hong, Chi Chen

AU - Thompson, Henry J.

AU - Jiang, Cheng

AU - Hammond, Geoffrey L.

AU - Tritchler, David

AU - Yaffe, Martin

AU - Boyd, Norman F.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL→MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/detoxification of catecholestrogens. Subjects were recruited across five categories of breast density. Risk factor information, anthropometric measures, and blood samples were obtained; sex hormone and growth factor levels were measured, and COMT genotypes determined. Mammograms were digitized and measured using a computer-assisted method. After adjustment for age and ethnicity, among pre- but not postmenopausal subjects, each low-activity COMT*2 allele was associated with lower levels of percentage breast density. The statistical significance of this association was lost after further adjustment for serum growth factors [growth hormone, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3)], hormones [follicle-stimulating hormone (FSH) and progesterone], and body size (body mass index and waist:hip ratio). The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.

AB - Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL→MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/detoxification of catecholestrogens. Subjects were recruited across five categories of breast density. Risk factor information, anthropometric measures, and blood samples were obtained; sex hormone and growth factor levels were measured, and COMT genotypes determined. Mammograms were digitized and measured using a computer-assisted method. After adjustment for age and ethnicity, among pre- but not postmenopausal subjects, each low-activity COMT*2 allele was associated with lower levels of percentage breast density. The statistical significance of this association was lost after further adjustment for serum growth factors [growth hormone, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3)], hormones [follicle-stimulating hormone (FSH) and progesterone], and body size (body mass index and waist:hip ratio). The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.

UR - http://www.scopus.com/inward/record.url?scp=0141563677&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141563677&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 838

EP - 847

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 9

ER -