An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer

Jackie A. Lavigne, Kathy J. Helzlsouer, Han Yao Huang, Paul T. Strickland, Douglas A. Bell, Ornella Selmin, Mary A. Watson, Sandra Hoffman, George W. Comstock, James D. Yager

Research output: Contribution to journalArticle

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Abstract

Mounting evidence suggests that catechol metabolites of estradiol may contribute to the development of estrogen-induced cancers. O-Methylation, catalyzed by catechol-O-methyltransferase (COMT), inactivates catechol estrogens. COMT is polymorphic in the human population, with 25% of Caucasians being homozygous for a low activity allele of the enzyme (COMT(LL)). We hypothesized that low activity COMT may be a risk factor for human breast cancer and designed a PCR-based RFLP assay to determine COMT genotype in a cohort of 112 matched, nested case-control samples. In the total study population, the odds ratios for the association of breast cancer risk with COMT(HL) and COMT(LL) genotypes were 1.30 [confidence interval (CI), 0.66-2.58] and 1.45 (CI, 0.69-3.07), respectively. Postmenopausal COMT(LL) women had a greater than 2-fold increased risk of developing breast cancer [odds ratio (OR), 2.18; CI, 0.93-5.11]. The association of COMT(LL) with the development of postmenopausal breast cancer was stronger and statistically significant in those women with a body mass index >24.47 kg/m2 (OR, 3.58; CI, 1.07-11.98). When COMT(LL) was combined with either glutathione S-transferase (GST) M1 null or with GSTP1 Ile-105-Val/Val-105- Val (intermediate/low activity, respectively) genotypes, the risk for developing postmenopausal breast cancer was also significantly increased. Our findings suggest that the allele encoding low activity COMT may be an important contributor to the postmenopausal development of breast cancer in certain women.

Original languageEnglish (US)
Pages (from-to)5493-5497
Number of pages5
JournalCancer Research
Volume57
Issue number24
StatePublished - Dec 15 1997
Externally publishedYes

Fingerprint

Catechol O-Methyltransferase
Alleles
Breast Neoplasms
Confidence Intervals
Odds Ratio
Genotype
Catechol Estrogens
Restriction Fragment Length Polymorphisms
Methylation
Population
Estradiol
Estrogens
Body Mass Index

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lavigne, J. A., Helzlsouer, K. J., Huang, H. Y., Strickland, P. T., Bell, D. A., Selmin, O., ... Yager, J. D. (1997). An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. Cancer Research, 57(24), 5493-5497.

An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. / Lavigne, Jackie A.; Helzlsouer, Kathy J.; Huang, Han Yao; Strickland, Paul T.; Bell, Douglas A.; Selmin, Ornella; Watson, Mary A.; Hoffman, Sandra; Comstock, George W.; Yager, James D.

In: Cancer Research, Vol. 57, No. 24, 15.12.1997, p. 5493-5497.

Research output: Contribution to journalArticle

Lavigne, JA, Helzlsouer, KJ, Huang, HY, Strickland, PT, Bell, DA, Selmin, O, Watson, MA, Hoffman, S, Comstock, GW & Yager, JD 1997, 'An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer', Cancer Research, vol. 57, no. 24, pp. 5493-5497.
Lavigne, Jackie A. ; Helzlsouer, Kathy J. ; Huang, Han Yao ; Strickland, Paul T. ; Bell, Douglas A. ; Selmin, Ornella ; Watson, Mary A. ; Hoffman, Sandra ; Comstock, George W. ; Yager, James D. / An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. In: Cancer Research. 1997 ; Vol. 57, No. 24. pp. 5493-5497.
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abstract = "Mounting evidence suggests that catechol metabolites of estradiol may contribute to the development of estrogen-induced cancers. O-Methylation, catalyzed by catechol-O-methyltransferase (COMT), inactivates catechol estrogens. COMT is polymorphic in the human population, with 25{\%} of Caucasians being homozygous for a low activity allele of the enzyme (COMT(LL)). We hypothesized that low activity COMT may be a risk factor for human breast cancer and designed a PCR-based RFLP assay to determine COMT genotype in a cohort of 112 matched, nested case-control samples. In the total study population, the odds ratios for the association of breast cancer risk with COMT(HL) and COMT(LL) genotypes were 1.30 [confidence interval (CI), 0.66-2.58] and 1.45 (CI, 0.69-3.07), respectively. Postmenopausal COMT(LL) women had a greater than 2-fold increased risk of developing breast cancer [odds ratio (OR), 2.18; CI, 0.93-5.11]. The association of COMT(LL) with the development of postmenopausal breast cancer was stronger and statistically significant in those women with a body mass index >24.47 kg/m2 (OR, 3.58; CI, 1.07-11.98). When COMT(LL) was combined with either glutathione S-transferase (GST) M1 null or with GSTP1 Ile-105-Val/Val-105- Val (intermediate/low activity, respectively) genotypes, the risk for developing postmenopausal breast cancer was also significantly increased. Our findings suggest that the allele encoding low activity COMT may be an important contributor to the postmenopausal development of breast cancer in certain women.",
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AU - Strickland, Paul T.

AU - Bell, Douglas A.

AU - Selmin, Ornella

AU - Watson, Mary A.

AU - Hoffman, Sandra

AU - Comstock, George W.

AU - Yager, James D.

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