Dataset Information

Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

ABSTRACT: Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 controls) in a Spanish population. Furthermore, we have performed a meta-analysis including 20,098 subjects (7,998 cases and 12,100 controls) to summarize the data available for rs10046 and breast cancer risk. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association. The results of our case-control study show an association between the carriers of at least one C allele (dominant model) and breast cancer risk (OR?=?1.29, 95% CI 1.01-1.66, p-value?=?0.038). The meta-analysis shows no significant association with breast cancer risk in any of the genetic models tested. The analysis by ethnic subgroups also failed to produce associations. The evaluation of heterogeneity, influence analysis, and publication bias confirms the reliability of the analysis. We can conclude that the rs10046 polymorphism on CYP19 by itself does not constitute breast cancer risk. We cannot, however, reject the possibility that it could contribute (interact), together with other genetic variants, to modify the circulating levels of estradiol.

SUBMITTER: Pineda B

PROVIDER: S-EPMC3547044 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

Pineda Begoña B García-Pérez Miguel Ángel MÁ Cano Antonio A Lluch Ana A Eroles Pilar P

PloS one 20130116 1

Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To ...[more]

PMID: 23342035

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Project description:BackgroundBreast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population.MethodsA case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed.ResultsGenotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006).ConclusionsWe have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

Project description:BACKGROUND:The X-ray repair cross-complementing group 3 (XRCC3) is an efficient component of homologous recombination and is required for the preservation of chromosomal integrity in mammalian cells. The association between Thr241Met single-nucleotide polymorphism (SNP) in this gene and susceptibility to breast cancer has been assessed in several studies. Yet, reports are controversial. The present meta-analysis has been designed to identify whether this SNP is associated with susceptibility to breast cancer. METHODS:We performed a systematic review and meta-analysis for retrieving the case-control studies on the associations between T241?M SNP and the risk of breast cancer. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to verify the association in dominant, recessive, and homozygote inheritance models. RESULTS:We included 55 studies containing 30,966 sporadic breast cancer cases, 1174 familial breast cancer cases and 32,890 controls in the meta-analysis. In crude analyses, no association was detected between the mentioned SNP and breast cancer risk in recessive, homozygote or dominant models. However, ethnic based analysis showed that in sporadic breast cancer, the SNP was associated with breast cancer risk in Arab populations in homozygous (OR (95% CI)?=?3.649 (2.029-6.563), p?=?0.0001) and recessive models (OR (95% CI)?=?4.092 (1.806-9.271), p?=?0.001). The association was significant in Asian population in dominant model (OR (95% CI)?=?1.296, p?=?0.029). However, the associations was significant in familial breast cancer in mixed ethnic-based subgroup in homozygote and recessive models (OR (95% CI)?=?0.451 (0.309-0.659), p?=?0.0001, OR (95% CI)?=?0.462 (0.298-0.716), p?=?0.001 respectively). CONCLUSIONS:Taken together, our results in a large sample of both sporadic and familial cases of breast cancer showed insignificant role of Thr241Met in the pathogenesis of this type of malignancy. Such results were more conclusive in sporadic cases. In familial cases, future studies are needed to verify our results.

Dataset Information

Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

Publications

Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

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