Abstract:
Introduction: The prolonged exposure to estrogen is well established risk
factor for breast cancer which is the most common malignancy among
Sudanese women. The effect of estrogen hormone on target tissues is mediated
by its alpha receptor, through the binding of the hormone to the receptor which
in turn promote the proliferation and differentiation of mammary tissues. The
estrogen receptor alpha is coded by polymorphic ESR1 gene.
Objective: To evaluate the association between rs2234693, rs9340799 and
rs1801132 single nucleotide polymorphisms on ESR1 gene and breast cancer
risk, type and the receptor status.
Methodology: Three single nucleotide polymorphisms were genotyped in 139
breast cancer cases and 139 age-matched cancer-free controls. Leucocytes
DNA was extracted and genotyped by PCR-RFLP method. The estrogen
receptor status for 65 cases were determined on a freshly obtained breast
tissues according to standard histological procedures.
Results: The results of breast cancer cases showed a young mean age
46.5±10.4SD years, high frequencies of married women 97.1%, and parity
89.9%. The family history of breast or other type of female cancers in
Sudanese women, proved to be the strongest risk factor, with 12 folds increase
in the risk of developing breast cancer (OR=11.8, 95% CI:4-34.2, P-0). Of all
the three studied SNPs, rs9340799 (XbaI) was the only one to show
statistically significant association with the risk of breast cancer (P-0.03),
where unadjusted logistic regression of the genotypic variants of this SNP
showed that Xx genotype had (OR=1.6, 95% CI:0.85-3.04, P-0), and xx
genotype (OR=2.6, 95% CI:1.23-5.46, P-0.01). The association of genotypic
variants of different SNPs with estrogen receptor status, showed a statistically
significant association between Xx variant of (XbaI) with positive receptor
status (OR= 5.3, 95% CI:1.8-15.8, P-0.002). The other two SNPs (PvuII and
HinfI) showed statistically significant association only with mammographic
density (P-0.0 and 0.01 respectively).
Discussion: The family history of female cancers and SNPs, rs9340799 (XbaI)
are possible risk factors affecting breast cancer in Sudanese women.
