Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

Br J Cancer. 1999 Aug;80(11):1838-43. doi: 10.1038/sj.bjc.6690608.

Abstract

The incidence of breast cancer has been greatly increasing in Taiwan over the past two decades. Since cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens or oestrogen, we hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for breast cancer. This hypothesis was evaluated in this case control study of 150 breast cancer patients and 150 healthy controls among Chinese women. Two CYP1A1 polymorphisms were studied, one containing a new Msp1 site and the other located in axon 7 and resulting in the replacement of an isoleucine (Ile) residue by a valine (Val). After simultaneously considering the known or significant risk factors for breast cancer, including the age of study participants, positive family history of breast cancer, early menarche (< or = 13 years), nulliparity and late first full-term pregnancy (> or = 30 years), hormone replacement therapy and smoking, the CYP1A1 Msp1 polymorphism was found to be a significant factor in determining the risk of breast cancer. The homozygous variant was the most susceptible genotype with an adjusted odds ratio of 1.98 (95% confidence interval (CI) = 1.01-3.99) compared with the non-homozygous variants (the homozygous wild-type and the heterozygous variant). In contrast, the CYP1A1 Ile/Val polymorphism was not significantly associated with breast cancer development (adjusted OR = 1.07, 95% CI = 0.64-1.78). Interestingly, the Msp1 polymorphism was especially significant in postmenopausal women, but not in premenopausal women. Further stratification analysis in postmenopausal women who were non-smokers and with no history of hormone replacement therapy showed the cancer risk due to the Msp1 variant to be more significant in women with early menarche. We conclude that CYP1A1 polymorphism is a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Further study with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Asian Continental Ancestry Group / genetics*
  • Body Mass Index
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics*
  • China / ethnology
  • Contraceptives, Oral
  • Cytochrome P-450 CYP1A1 / genetics*
  • Estrogen Replacement Therapy
  • Exons
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Humans
  • Incidence
  • Isoleucine
  • Menarche
  • Middle Aged
  • Parity
  • Polymorphism, Genetic*
  • Pregnancy
  • Risk Factors
  • Smoking
  • Taiwan / epidemiology
  • Valine

Substances

  • Contraceptives, Oral
  • Isoleucine
  • Cytochrome P-450 CYP1A1
  • Valine