Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: A case-control study

Abstract

Abstract. Breast cancer (BC) is a complex disease influenced by environmental and genetic factors. The disease has important genetic and environmental components, most of them are still unknown. An important role of gene polymorphisms related to the risk of developing BC has been reported. However, the results have been controversial. We investigated the association of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms with breast carcinoma in women from Canary Islands (Spain). Blood samples collected from 135 patients with BC and 304 healthy controls all of them Caucasian, were analyzed through polymerase chain reaction-restriction fragment length polymorphism. Subsequently, a structured questionnaire including patient history and risk factors in relation to BC development was filled out. Allelic frequencies of these genetic variations were: TSER, (2) 0.55 and (3) 0.45 in cases, 0.49 and 0.51 respectively in controls (P=0.240); MTHFR C677T, (C) 0.63 and (T) 0.37 in cases, 0.60 and 0.40 respectively in controls (P=0.568); p53 Arg72Pro, (Arg) 0.74 and (Pro) 0.26 in cases and controls (P=0.910); MDR1 C3435T, (C) 0.52 and (T) 0.48 in cases, 0.55 and 0.45 respectively in controls (P=0.523). We did not observe any gene polymorphism as a risk factor to develop BC. A statistical association was observed between p53 codon 72 polymorphism and family history of breast cancer in both groups, as well as between MDR1 C3435T and smoking habits in cases (P<0.05). Gene polymorphisms vary by regions. The present study contributes to the characterization of the genetic pattern of the Canary population.

Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population

“…Allele, genotype, and phenotype frequencies in the PRE and POST groups were also not significantly different (P > 0.5). Our results are very similar to those reported for Spanish women (Henríquez-Hernández et al, 2009, suggesting the importance of ethnic factors in determining BC susceptibility.…”

“…Recent studies have investigated the association between the TS 3'-UTR del6 polymorphism and risk of several types of cancer, including breast cancer; however, the results have been inconsistent (Trinh et al, 2002;Henríquez-Hernández et al, 2009Wang et al, 2011;Zhou et al, 2012). In the present study, we found that the TS 3'-UTR del6 allele showed a small increase in both allelic and genotypic frequencies in the PRE group, but this increase was not significant (P > 0.05).…”

“…BC is a complex disease influenced by environmental and genetic factors, but most of these factors are unknown. Contributing factors include age, ethnicity, reproductive factors, hormones, familial history, lifestyle, and breast density (Henríquez-Hernández et al, 2009). Genetic alterations induced by endogenous or exogenous metabolites may also contribute to its etiology (Hashemi et al, 2012).…”

MDR1 C3435T polymorphism in Mexican patients with breast cancer

“…However, allele and genotype frequencies differ among diverse populations with breast cancer (Ashariati, 2008;Rodrigues et al, 2008;George et al, 2009;Henríquez-Hernández et al, 2009;Taheri et al, 2010;Fang et al, 2013). In addition, we observed that the T/T genotype appears to have a protective effect in the FCC group, whereas no association was found with IDBC.…”

Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan

“…In Caucasians, the 3435 frequency was reported as CC (22%), CT (50%), and TT (28%) (Hamidovic et al, 2010). In a study conducted among Spanish breast cancer patients MDR1 C3435T allele distribution was (C) 0.52 and (T) 0.48 which were not different from controls, while genotypes were distributed as CC 14 (28%), CT 24 (48%) and TT 12 (24%) (Henriquez-Hernandez et al, 2009). On the other hand, in Korean population, CC, CT, and TT genotypes were found in 50.9%, 10.2%, and 38.9% BC patients, respectively.…”