Genetic Variations in Cytochrome P450 1A1 and 1B1 Genes in a Cohort of Patients from Iraq Diagnosed with Breast Cancer

Abstract

Breast cancer is the most prevalent malignant neoplasm in females. Genetic variations in the xenobiotic metabolising cytochrome enzymes; Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in the individual susceptibility to breast cancer and its prognosis. The goal of this study is to estimate the incidence of single nucleotide polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI, and rs4646903/MSP1) and in CYP1B1 (rs1056836, Leu432Val) genes in patients with breast cancer. This case-control study included 180 female patients with breast cancer and 180 healthy control subjects from Kirkuk/Iraq. Genomic DNA was extracted from venous blood samples and tested for SNPs by the direct DNA sequencing technique. A statistical analysis was done to identify if there is any association between SNPs and the increasing odd of breast cancer and its stage, grade and molecular subtype at diagnosis. The common (reference) genotype of CYP1A1 gene rs1048943 is AA. The AG and GG variant genotypes were significantly more common in the breast cancer patients and conferred an increased odd of breast cancer and its later stages (stages III and IV) and poor differentiation ( P < .01) but not with the molecular subtypes. The common genotype of CYP1A1 rs4646903 is TT. The variant genotypes TC and CC are not associated either with increased risk of breast cancer ( P > .05) or with its stage, grade or molecular subtypes ( P > .05). The GG genotype of CYP1B1 rs1056836 was the common genotype. The CG and CC variant genotypes were not associated with the increased risks of breast cancer ( P > .05) or its stage, grade or molecular subtypes ( P > .05). In conclusion, variants genotypes of CYP1A1 rs1048943 might play a role in breast cancer pathogenesis and prognosis and can have a place in cancer screening and tailored medicine in the future in the Iraqi population. Future larger scale studies including other genes might help to better understand the role of the SNP in breast risk and its prognosis.

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

“…Various studies have shown the significance of CYP 450 polymorphism in the susceptibility to cancer. In hormone-related cancers such as breast cancer ( 53 ) and prostate cancer ( 54 ), CYP 450, which is involved in steroid hormone metabolism, affects cancer susceptibility. Studies have shown that patients carrying a mutation of the CYP1A1/2, CYP2D6, and CYP2E1 have an increased risk of head and neck squamous cell carcinoma, esophageal carcinoma, and lung carcinoma, arising from a deficiency in metabolizing carcinogens to their inactive derivatives ( 55 , 56 ); alcohol and nicotine are common carcinogens.…”

Association of rs4646903 and rs1048943 CYP1A1 estrogen-metabolizing gene polymorphisms with estrogen receptor-positive breast cancer in Kenyan women

“…An increase in the proportion of the variant genotype CC of rs4646903 with breast cancer stage was reported in contrast to no significant association between genetic polymorphisms of rs4646903 and breast cancer in East Asian, Caucasian, or African populations [31]. A study showed no association between the variant genotypes TC and CC and breast cancer, stage, grade, or molecular sub-type in Iraqi women diagnosed with breast cancer [28]. A study on a southern Indian population indicated a positive association of the variant genotypes TT and TC with breast cancer [13] where a 5-fold association of rs4646903 variant genotype CC supports the role of CYP1A1 in breast cancer susceptibility.…”

“…The three genotypes were TT (wild type), TC (variant heterozygous) and CC (variant homozygous) [26]. The MspI restriction enzyme identifies the CYP1A1 (rs4646903) polymorphism in the non-coding region of the gene [28].…”