The association between BRCA1 gene polymorphism and cancer risk: a meta-analysis

Abstract

Many studies have reported that BRCA1 polymorphisms are associated with cancer risk, but the results remain controversial. The purpose of this meta-analysis is to evaluate the relationship between BRCA1 polymorphisms (rs799917, rs1799950, rs1799966, or rs16941) and cancer risk. Relevant studies were identified via a systematic search of the PubMed, Embase, and Web of Science databases up to July 31, 2017. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to examine the strength of the associations. Thirty-five studies published in 19 publications involving 28,094 cases and 50,657 controls were included in this meta-analysis. There was no obvious association between rs799917, rs1799966, or rs16941 polymorphisms and overall cancer risk in any genetic models. However, subgroup analyses revealed that the rs799917 polymorphism could decrease the risk of cervical cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, and non-Hodgkin lymphoma (NHL) among Asian populations in one or more genetic models and that rs16941 could increase overall cancer risk among Caucasian populations in the homozygote and recessive models. Our meta-analysis also indicated that rs1799950 could decrease the breast cancer (BC) risk among Caucasian populations in the homozygote and recessive models. In summary, our results suggest that BRCA1 polymorphisms may play an important role in the etiology of cancer. However, due to the limited number of studies, these findings should be confirmed by new studies with larger sample sizes that address various types of cancer.

<p>The Impact of the Genetic Polymorphism in DNA Repair Pathways on Increased Risk of Glioblastoma Multiforme in the Arab Jordanian Population: A Case–Control Study</p>

“…However, when dealing with cancers as subgroups, they found that among Asian populations, the rs799917 polymorphism is associated with decreased risk of esophageal squamous carcinoma, gastric carcinoma, cervical cancer, and non-Hodgkin lymphoma. 51 This study is the first to address the relationship between BRCA1 rs1799966 and rs799917 SNP, and the risk of GBM among the Arab Jordanian population. The findings of the study show that BRCA1 rs799917 is associated with decreased risk of GBM in the recessive model (AA vs G/ G-A/G: OR, 0.46, 95% CI, 0.26-0.82, p=0.01) and the same SNP is associated with increased risk of GBM in the overdominant model (AG vs G/G-A/A: OR, 1.72, 95% CI, 1.02--2.89, p=0.04).…”

Screening of BRCA1 variants c.190T>C, 1307delT, g.5331G>A and c.2612C>T in breast cancer patients from North India

“…The wild type genotype (CC) was associated with increased risk of gastric cancer (Wang et al, 2015), esophageal squamous cell carcinoma (ESCC) (Zhang et al, 2013) and non-Hodgkin Lymphoma (NHL) (Chen et al, 2013), but not associated with thyroid carcinoma (Xu et al, 2012) and ovarian cancer (Wenham et al, 2003;Auranen et al, 2005). In a recent meta-analysis (Xu et al, 2018), the p.Pro871Leu polymorphism was linked to decreased risk of various cancers like ESCC, cervical cancer, gastric cancer and NHL among Asians. But some studies from Chinese populations have reported significant associations between the BRCA1 p.Pro871Leu variant and breast cancer, where the CT genotype provides increased risk to breast cancer in these populations (Huo et al, 2009;Wang et al, 2009).…”

“…Genomic DNA was extracted from peripheral blood lymphocytes by a standard phenol-chloroform method (Adeli and Ogbonna, 1990). Four variants of BRCA1, c.190T>C (p.Cys64Arg), 1307delT, g.5331G>A (p.G1738R) and c.2612C>T (p.Pro871Leu) were screened by a PCR-RFLP method using published primer sequences (Gajalakshmi et al, 2007;Karami and Mehdipour, 2013;Xu et al, 2018).…”

“…The variant c.2612C>T (p.Pro871Leu) is a nonsynonymous polymorphism of BRCA1 that leads to the substitution of proline by leucine at position 871, a region where recombinase RAD51 interacts with BRCA1 to aid homologous recombination (Miao et al, 2017). The T allele has been reported to show an association with breast cancer risk in Chinese populations (Xu et al, 2018) though some studies have reported no significant association between the p.Pro871Leu variant of BRCA1 and breast cancer risk. The 1307delT variant of BRCA1, present in codon 396 of exon 11, causes a frameshift mutation that introduces a premature stop codon at amino acid residue 409 and leads to protein truncation.…”

Non-random distribution of gastric cancer susceptible loci on human chromosomes

“…Table 1 (Tab. 1) (References in Table 1: Chang et al, 2014[ 1 ]; Chen et al, 2015[ 2 ]; Cheng et al, 2015[ 3 ]; Dai et al, 2015[ 4 ]; Deng et al, 2014[ 5 ]; Gong et al, 2016[ 9 ]; Han et al, 2012[ 11 ]; He et al, 2013[ 12 ]; Hua et al, 2014[ 14 ]; Jia et al, 2017[ 16 ]; Kuang et al, 2014[ 17 ]; Li et al, 2015[ 20 ]; Li et al, 2016[ 18 ]; Li et al, 2017[ 19 ]; Liang et al, 2018[ 21 ]; Liu et al, 2011[ 23 ]; Liu et al, 2011[ 24 ]; Liu et al, 2014[ 25 ]; Liu et al, 2014[ 26 ]; Lu et al, 2012[ 27 ]; Ma et al, 2013[ 29 ]; Ma et al, 2013[ 30 ]; Ma et al, 2017[ 28 ]; Mo et al, 2016[ 31 ]; Mocellin et al, 2015[ 32 ]; Namazi et al, 2018[ 35 ]; Pabalan et al, 2015[ 36 ]; Peng and Xu, 2015[ 37 ]; Qi et al, 2016[ 38 ]; Qin et al, 2017[ 39 ]; Ribeiro et al, 2017[ 41 ]; Shen et al, 2014[ 47 ]; Shi et al, 2014[ 48 ]; Shi et al, 2017[ 49 ]; Shi et al, 2018[ 50 ]; Tian et al, 2012[ 52 ]; Wang et al, 2013[ 53 ]; Wang et al, 2014[ 54 ]; Wang et al, 2015[ 56 ]; Wang et al, 2015[ 57 ]; Wang et al, 2016[ 55 ]; Wu et al, 2015[ 58 ]; Xie et al, 2017[ 59 ]; Xu et al, 2014[ 61 ]; Xu et al, 2014[ 63 ]; Xu et al, 2015[ 62 ]; Xu et al, 2018[ 60 ]; Yadav et al, 2018[ 64 ]; Yan et al, 2013[ 65 ]; Yang et al, 2014[ 66 ]; Yang et al, 2016[ 67 ]; Ye et al, 2017[ 68 ]; Yu et al, 2014[ 69 ]; Zhang et al, 2012[ 72 ]; Zhang et al, 2013[ 71 ]; Zhang et al, 2015[ 74 ]; Zhang et al,...…”