Abstract

CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI- RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p-value = 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p-value= 0.95; OR= 0.95; 95% CI= 0.51- 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.

Highlights

  • Breast cancer is the most common female malignancy worldwide

  • The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in cytochrome P450 1A1 (CYP1A1) and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history

  • No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p= 0.55; odds ratios (OR) = 0.77; 95% confidence intervals (95% CI)= 0.32 - 1.83) nor with the M4 polymorphism (p= 0.95; OR= 0.95; 95% CI= 0.51- 1.88)

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Summary

Introduction

Breast cancer is the most common female malignancy worldwide. According to the latest statistics in 2010, breast cancer ranked first among cancers in Jordanian women accounting for 37.4% of all female cancers (Tarawneh et al, 2010). CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. Purpose: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Results: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p= 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p= 0.95; OR= 0.95; 95% CI= 0.51- 1.88). Conclusions: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females

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