Abstract
BackgroundBreast cancer is reported to cause the highest mortality among female cancer patients. Previous studies have explored the association of silent mating-type information regulator 2 homolog 1 (SIRT1) gene expression with prognosis in breast cancer. However, no studies exist, so far, on the role of SIRT1 gene polymorphism in breast cancer risk or prognosis. The present study aimed to assess the association between SIRT1 gene polymorphisms and breast cancer in Egyptians.MethodsThe study comprised 980 Egyptian females divided into a breast cancer group (541 patients) and a healthy control group (439 subjects). SIRT1 gene single nucleotide polymorphisms (SNPs) rs3758391, rs3740051 and rs12778366 were genotyped using real-time polymerase chain reaction (RT-PCR). Allelic and genotypic frequencies were determined in both groups and association with breast cancer and clinicopathological characteristics was assessed.ResultsBreast cancer patients exhibited elevated serum SIRT1 levels which varied among different tumor grades. SIRT1 rs3758391 and rs12778366 TT genotypes were more frequent, exhibited higher SIRT1 levels than CC and CT genotypes and were associated with histologic grade and lymph node status. SIRT1 rs12778366 TT genotype also correlated with negative estrogen receptor (ER) and progesterone receptor (PR) statuses. The T allele frequency for both SNPs was higher in breast cancer patients than in normal subjects. Combined GG and AG genotypes of rs3740051 were more frequent, showed higher serum SIRT1 levels than the AA genotype, and were associated with ER and PR expression. Furthermore, inheritance of the G allele was associated with breast cancer.ConclusionsOur findings reveal that rs3758391 and rs12778366 polymorphisms of SIRT1 gene are associated with breast cancer risk and prognosis in the Egyptian population.
Highlights
Sirtuin 1 (SIRT1) is 1 of 7 members of the sirtuin family of nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase that are human homologues of yeast silent mating-type information regulator 2 [1]
Breast cancer patients exhibited elevated serum SIRT1 levels which varied among different tumor grades
SIRT1 rs12778366 TT genotype correlated with negative estrogen receptor (ER) and progesterone receptor (PR) statuses
Summary
Sirtuin 1 (SIRT1) is 1 of 7 members of the sirtuin family of nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase that are human homologues of yeast silent mating-type information regulator 2 (sir2) [1]. Wang et al [13] analyzed a public database and found that SIRT1 expression was reduced in many other types of cancers, including glioblastoma, bladder carcinoma, prostate carcinoma and ovarian cancers as compared to the corresponding normal tissues. Their further analysis of 44 breast cancer and 263 hepatic carcinoma cases revealed reduced expression of SIRT1 in these tumors [13]. The present study aimed to assess the association between SIRT1 gene polymorphisms and breast cancer in Egyptians
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