ABSTRACT
MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.
Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Ethnicity , Female , Genetic Predisposition to Disease , Genotype , Humans , Mexico , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Postmenopause , Premenopause , Risk FactorsABSTRACT
Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre- and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate inter-and intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.
Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic , Thymidylate Synthase/genetics , 3' Untranslated Regions/genetics , 5' Untranslated Regions/genetics , Adult , Alleles , Female , Gene Frequency , Genotype , Haplotypes , Humans , INDEL Mutation , Mexico , Middle Aged , Polymorphism, Single Nucleotide , Postmenopause/genetics , Premenopause/genetics , Risk Factors , Tandem Repeat Sequences/genetics , Young AdultABSTRACT
Lymphoma L-5178-Y bearing Balb/c mice were unable to mount a delayed-type hypersensitivity reaction to dinitrofluorobenzene (DNFB). A suppressor factor present in the ascitis of these mice inhibited the response if given during DNFB sensitization, but not during challenge. The factor was not present in lymphoma-bearing Balb/c nu/nu mice. It appeared to be a 35-66 kDa protein. Non-specific esterase staining indicated that the spleens of tumor-bearing and ascitis-injected mice contained a large excess of macrophages. Our observation that the suppressor factor prevented the very start of the immune response may indicate why immunostimulation is difficult to obtain in cancer bearing hosts.
