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Genotyping of tamoxifen
metabolizing enzyme (CYP2D6*4) and its clinical impact in
breast cancer patients
C. Kalyana Kumar, Mohan Reddy, Kaiser Jamil* and Mohana
Vamsy
Research
Department, Indo American Cancer Institute and Research
Center, Banjara Hills, Road No 14, Hyderabad, Andhra
Pradesh, India. 2Bhagwan Mahavir Medical Research Center,
10-1-1, Mahavir Marg, A.C.Guards, Hyderabad- 500004, A. P.
India.
*Corresponding author.
E-mail:
kaiser.jamil@gmail.com.
Accepted
16 November 2009. |
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Tamoxifen is a non-steroidal antiestrogen drug widely used
in the treatment of breast cancer and metabolized by CYP2D6.
In this study, we compared the patients who were receiving
either tamoxifen or other chemo drugs, forming a two-arm
study. We genotyped 140 tamoxifen treated postmenopausal
women with breast cancer, 140 non-tamoxifen treated pre and
postmenopausal women with breast cancer and 124 controls,
using PCR-RFLP method. In arm-1 study CYP2D6 genotype
frequencies of metabolizers were classified as extensive
metabolizers (EM) 70% (n = 98), intermediate metabolizers
(IM) 30% (n = 42) in tamoxifen treated cases and 85% (n =
118), 15% (n = 22) in non-tamoxifen treated cases
respectively. Tamoxifen treated IM -carriers showed 24.32%
(n = 9) recurrence. Recurrent cases were not found in non-tamoxifen
treated group. CYP2D6*4 allele carriers were high but this
allele carrier was found to reduce the risk of recurrence
when treated with tamoxifen. In arm-2 study CYP2D6 genotype
frequencies of EM, IM and Poor metabolizers (PM) were 79.57%
(n = 113), 14.08% (n = 20), 6.33% (n = 9) in non tamoxifen
treated breast cancer cases. In controls the EM, IM, and PM
genotypes were 93.54% (n = 116), 5.64%) (n = 7) and 0.80% (n
= 1) respectively. Statistical analysis indicated that p
value of both IM (P- value 0.03) and PM (P- value 0.04)
carriers were associated with the risk of breast cancer. PM
showed poor therapeutic outcome, which may be due to low
level of the tamoxifen metabolite-endoxifen.
Key
words:
Breast cancer, Tamoxifen, CYP2D6*4, Poor metabolizers (PM),
Extensive metabolizers (EM), Intermediate metabolizers (IM). |
