Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study

Abstract

BackgroundGenetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population.MethodsWe genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses.ResultsERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34–6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17–5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected.Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction.Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7–8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and larger tumor (T4). We did not find any MTHFR haplotypes associated with BC susceptibility. However, the less common haplotype MTHFR T-C was more frequent in young patients and in familial breast cancer, while MTHFR C-C haplotype was associated with sporadic BC form.ConclusionsOur findings are a first observation of association between ERCC2 SNPs and breast cancer in Moroccan population. The results suggested that ERCC2 and MTHFR polymorphisms may be reliable for assessing risk and prognosis of BC in Moroccan population.

Strong Correlation of MTHFR Gene Polymorphisms with Breast Cancer and its Prognostic Clinical Factors among Egyptian Females

“…Furthermore, in this study, the frequency of T allele of MTHFR C677T in patients was 54.5% vs.16.7% in controls with highly significant value (P= 0.001), indicating that the risk of breast cancer increases by 5.98 times in individual carrying the T allele. These results are supported by previous studies conducted on different populations as Indian and Moroccan suggesting that this polymorphism could be a therapeutic target for breast cancer (Waseem et al, 2016;Hardi et al, 2018;Rahimi et al, 2019). On the other hand, some previous case-control studies of: Mexican, north Indian, Turkish and Chinese population did not report any relation (Mir et al, 2008;Ramos-Silivia et al, 2015;Kaya et al, 2016;Song et al, 2016).…”

“…However, there was no correlation of our data with age or disease onset. Other studies on Moroccan and Indian cases reported no statistical significant association with clinicopathological characteristics (Waseem et al, 2016;Hardi et al, 2018;Karimian et al, 2020). Moreover, all our data were confirmed in multivariate analysis to improve the validity of the results and to identify the independent association between different genotypes of the MTHFR C677T (rs1801133) and MTHFR A1289C rs1801131 and BC.…”

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia

“…The questionnaire collected all information needed to identify the familial forms of BC compared to sporadic ones. In summary, the inclusion criteria adopted for identified family forms were: one case with BC diagnosis before 39 years of age and/or bilateral diagnosis of BC before the age of 40 in two first or second degree relatives; presence of 3 or more cases of BC in first or second degree relatives in the same side of the family tree; cases of ovarian cancer; male BC cases; presence of multiple primary cancers in any organ in the same individual or family [22].…”

MTHFR C677T and A1298C polymorphisms and lung cancer risk in a female Chinese population

“…Hardi et al reported that rs1801133TT genotype could increase the susceptibility of breast cancer comparing with wild-type genotype. 22 A meta-analysis published in 2016 summarized that the MTHFR C677T polymorphism showed significant association with lung cancer in Asian and overall populations, but not in Caucasian populations. Xia et al have reported that MTHFR C677T polymorphism was a risk factor for gastric cancer and that A1298C played a protective role against gastric cancer.…”