Relationship of polymorphism cyp1b1*2 (ser119; rs1056827) on the pathway of estrogen metabolism with breast cancer risk in iranian women

Fereshteh Moheb afzali,1,* Zahra tahmasebi fard,2

1. Department of Molecular and Cellular Biology , Faculty of Advanced Science and Technology , Tehran Medical Sciences , Islamic Azad University , Tehran , Iran .
2. Department of Biology , Roudehen Branch , Islamic Azad University , Roudehen , IR Iran



The high prevalence of breast cancer and its heterogeneity, and considering that the population of iran is genetically and nutritionally different from other populations in the world, therefore, the study of genetic factors and the effect of polymorphisms on the function of proteins, as well as the effect of these enzymes on food metabolism can play an important role in controlling diseases. identification and screening of people before the onset of cancer or preventing the development of a disease with appropriate treatment can be effective in controlling cancer. the common polymorphism in the pathway of estrogen metabolism at the site of ala 119 ser )cyp1b1 * 2) codon results in a 2- to 4- fold increase in the the activity of the cyp1b1 enzyme compared to the natural enzyme. this results in a 2- to 4- fold increase in the hydroxylation of the procarsinogen to carcinogeniccompounds and the production of active metabolites that can damage shuffling and fracturing in single-stranded dna increases the risk of genetic mutations, including the potential for breast cancer. therefore, the aim of this study was to determine the relationship between homozygous genotypes and heterozygote polymorphism (rs 1056827) in breast cancer patients compared to controls, so that the results could be used for early screening and if found a meaningful relationship, this polymorphism was identified as one of the factors involved in breast cancer.


79 patients with breast cancer and 79 healthy women who were referred to shohada tajrish hospital were selected. their blood samples were then obtained, and a sample of their dnawas extracted. the genotypes of people were determined by assist of pcr-rflp techniques. our data was analyzed with x2 statistical test by spss 19 software.


In the patient group, age range was 32 - 70 years with average49.68 years and in the control group was 30 - 65 years with average 47.34 years. in the patient group the meanweight of the participants was 68 _ 8 kg and 61 _ 2 in the control group. according to the medical records of the patient group, estrogen receptor expression was observed in 58% and progesterone receptor expression in 42% of them. of the patient group, 26 (32.91%) had invasive lobular carcinoma, 45 (56.97%) had invasive ductal carcinoma, 5(6.33%) had ductal carcinoma in situ and 3 (3.79%) had lobular carcinoma in situ. 38 patients had metastatic breast cancer, 16 patients had grade iii breast cancer, 13 patients had grade ii/iii breast cancer and 12 patients had grade ii breast cancer. the frequencies of alleles and homozygote and heterozygote genotypes in this study comply with the rule of hardy-weinberg. in the cancer group, it was calculated that there were 42 cases (53.16%) of the tt genotype, 16 cases(20.25%) of the gg genotype and 21 cases (26.59%) of the tg genotype, whereas in the control group, there were 18(22.79%), 48 (60.76%) and 13 (16.45%) cases of tt, gg and tg genotypes, respectively. within this result, the risk was increased from 3.85-fold (95% ci 1.94-7.65, p value=0) in tt homozygote to 0.16 fold (95% ci 0.08-0.33, p value =0) in homozygotes for gg. the frequency of the g allele in the patient group was0.34, while in the control group it was 0.69. the frequency of the t allele in the patient and control groups were 0.66 and 0.31 respectively.


The results of statistical analysis showed that the presence of t allele in the polymorphism (rs 1056827) in exon2 (codon g119t) is associated with a risk of breast cancer. it seems that the catalytic functional differences of this enzyme in the presence of polymorphism is one of the reasons for the effect on estrogen metabolism and the creation of dna damaging agents.


Gene cyp 1b1, polymorphism , pcr-rflp, breast cancer