Affiliations: Indian Institute of Toxicology Research (Council of
Scientific and Industrial Research), Lucknow- 226 001, India | Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Lucknow- 226 014, India | Banaras Hindu University, Varanasi-221 005,
India
Note: [] Corresponding author: Mahendra Pratap Singh, Indian Institute of
Toxicology Research, Mahatma Gandhi Marg, Post Box- 80, Lucknow- 226 001, UP,
India. Tel.: +91 522 2620106/2614869 Ext. 337; Fax: +91 522 2628227; E-mail:
[email protected]
Abstract: Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase
(COMT) enzymes play critical roles in estrogen metabolism. Alterations in the
catalytic activity of CYP1B1 and COMT enzymes have been found associated with
altered breast cancer risk in postmenopausal women in many populations. The
substitution of leucine (Leu) to valine (Val) at codon 432 increases the
catalytic activity of CYP1B1, however, substitution of Val to methionine (Met)
at codon 158 decreases the catalytic activity of COMT. The present study was
performed to evaluate the associations of CYP1B1 Leu^{432}Val and/or COMT
Val^{158}Met polymorphisms with total, premenopausal and postmenopausal
breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls
and breast cancer patients were analyzed employing polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel
electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit
statistically significant association with breast cancer risks when analyzed
individually, COMT wild type (Val^{158}Val) in combination with CYP1B1
heterozygous variant (Leu^{432}Val) [OR: 0.21; 95% CI (0.05–0.82), p
value; 0.021] and COMT heterozygous variant (Val^{158}Met) in combination
with CYP1B1 wild type (Leu^{432}Leu) [OR: 0.29; 95% CI (0.08–0.96), p
value; 0.042] showed significant protective association with premenopausal
breast cancer risk. The results demonstrate that CYP1B1 wild type in
combination with COMT heterozygous or their inverse combination offer
protection against breast cancer in premenopausal Indian women.
Keywords: Breast cancer, genetic polymorphism, CYP1B1, COMT
