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Abstract
AbstractReported associations of CYP1A1 polymorphisms with breast cancer have been inconsistent. In this meta-analysis examining breast cancer associations of three CYP1A1 polymorphisms (M1, M2 and M4) among Indian women may yield information that may be of clinical and epidemiological use for this particular demography. We searched MEDLINE using PubMed and Embase for association studies. From seven published case-control studies, we estimated overall associations and applied subgroup analysis to explore differential effects. All three polymorphisms exhibited overall increased risk, significant in M1 (OR 1.61–1.65, p = 0.04) and M4 (OR 2.02–3.92, p = 0.02–0.04). Differential effects were observed only in the M1 polymorphism where M1 effects were significant in South Indians (OR 2.20–4.34, p < 0.0001) but not the North population, who were at reduced risk (OR 0.64–0.77, p = 0.03–0.55). These populations were not materially different in regard to M2 and M4 as did the women stratified by menopausal status. In this meta-analysis, M1 and M4 effects may render Indian women susceptible, but may be limited by heterogeneity of the studies. Differential effects of the M1 polymorphism in breast cancer render South Indians susceptible compared to those in the North.
Highlights
Breast cancer is a leading cause of death among women in India [1]
Differential effects were observed only in the M1 polymorphism where M1 effects were significant in South Indians but not the North population, who were at reduced risk
We find that meta-analysis is a useful tool to examine broad trends in CYP1A1 associations with breast cancer in Indian populations, and may avoid possible misleading conclusions based on only single-population studies
Summary
Breast cancer is a leading cause of death among women in India [1]. The multifactorial nature of this disease is marked by the synergy of interaction among various environmental and genetic factors [2,3]. One genetic factor is the CYP1A1 protein, encoded by CYP1A1 gene, an interesting candidate that might influence susceptibility to breast cancer risk for reasons mentioned by Chen et al [4]. CYP1A1 gene polymorphisms have been extensively studied, especially in relation to breast cancer susceptibility [4,5,6,7,8,9,10,11,12,13]. Of the four common polymorphisms of the CYP1A1 gene identified, we examine three in the Indian population: M1 (rs4646903: T3801C, giving rise to a MspI restriction site in the 3’-noncoding region [15], M2 (rs1048943: A2455G), resulting in an amino acid change at codon 462 from isoleucine to valine within the heme-binding domain of exon 7 [16]; and M4 (rs1799814: C2453A), resulting in an amino acid substitution of threonine with asparagine at codon 461 [17].
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