Association Of P73and CD44Single Nucleotide Polymorphisms With Biological Characteristics Of Breast Cancer

Objective: The aim of this study was to evaluate the association ofp73G4C14-to-A4T14(rs2273953and rs1801173) and CD44rs4756195single nucleotide polymorphisms with biological characteristics of breastcancer, and to evaluate the expression of CD44^＋/CD24^－/lowand theassociation between CD44^＋/CD24^－/lowand the response to anthracyclines-based chemotherapy in patients with breast cancer.Methods: In a case-control study, single nucleotide polymorphisms(SNPs) of p73G4C14-to-A4T14(rs2273953and rs1801173) at exon2and CD44rs4756195at intron1were genotyped by SequenomMassARRAY iPLEX GOLD System in170patients with breast cancerand178healthy controls. Data was analyzed via t test, Chi-square test andLogistic regression analysis. A total of91patients with breast cancerwere treated with anthracycline-based neoadjuvant chemotherapy, and theclinical response to the chemotherapy was obtained after2to3cycles.Double-staining immunohistochemistry was used to detect the expressionof CD44^＋/CD24^－/lowon paraffin-embedded tissues of pre-chemotherapy and post-chemotherapy. Data was analyzed via t test and Chi-square test.Results:1. The distribution of p73genotypes and allelotypes hadno significant difference between patients with breast cancer and healthycontrols (χ2=2.750,P=0.253；χ2=2.195,P=0.138). More risk ofdeveloping triple negative breast cancer (TNBC) was found in theindividuals who carried with GC/GC genotype than individuals carriedwith GC/AT and AT/AT genotypes (OR=2.99,95%CI=1.30-6.89,P=0.010).2. The frequencies of genotypes (AA, AG and GG) ofCD44rs4756195show a significant difference in the distributionof the genotypes between patients with breast cancer and healthy controls(χ2=6.272,P=0.043). The GG and AG genotype significantly increasedthe risk of developing breast cancer compared with AA genotype(OR=6.035,95%CI=1.262-28.856, P=0.024ï¼› OR=5.367,95%CI=1.166-24.709,P=0.031).3. There was no significant correlationbetween p73polymorphisms and the clinicopathological characteristics,such as age, tumor size, menopausal status, TNM classification,pathological type, axillary lymph nodes metastasis, estrogen receptor(ER),progesterone receptor(PR),human epidermal growth factorreceptor2(HER2), and so on (P＞0.05). The frequency of GC/GCgenotype in triple negative breast cancer (ER-negative, PR-negative andHER2-negative) was higher than non-triple negative breast cancer (78.9%vs57.6%, χ2=5.741, P=0.017).4. There was no significant correlation between CD44polymorphisms and the clinicopathological characteristics,such as age, tumor size, menopausal status, TNM classification,pathological type, and so on (P＞0.05). The rate of axillary lymph nodesmetastasis in patients with breast cancer who carried with GG genotypewas higher than those carried with AG and GG genotype(62.6%vs44.7%,χ2=4.473,P=0.034). The positive rate of CD44in patients with breastcancer who carried with AG and GG genotype was higher than thosecarried with GG genotype(68.1%vs45.5%,χ2=6.930,P=0.008).5. Theoverall response and the rate of pathological complete remission (pCR) ofthe patients with breast cancer who carried with p73G4C14-to-A4T14GC/GC genotype were not significant difference compared with thosecarried with AT/AT and GC/AT genotypes (OR=1.009,95%CI=0.414-2.461, P=0.984; OR=0.970,95%CI=0.372-2.527,P=0.950).6. The overall response of the patients with breast cancer whocarried with CD44rs4756195GG genotype was not significant differencecompared with those carried with AA and AG genotypes (73.6%vs69.0%, χ2=0.240, P=0.625), and the rate of pathological completeremission in breast cancer carried with AA and AG genotypes was higherthan those carried with GG genotype (55.2%vs16.5%,χ2=17,181,P=0.000ï¼›OR=13.935,95%CI=4.359-44.541,P=0.000).7. The expressionrate of CD44^＋/CD24^－/lowphenotype was39.6%(36/91). The proportionsof CD44⁺/CD24ï¹£/lowcells were significantly increased after anthracyclines-based chemotherapy (P=0.028).The positive rate of ER inCD44⁺/CD24^ï¹£/lowpositive group was lower than CD44⁺/CD24ï¹£/lownegative group(25.0%vs47.3%, P=0.033), and the expression rate ofCD44^＋/CD24^－/lowphenotype in triple negative breast cancer was higherthan non-triple negative breast cancer(61.9%vs32.9%, P=0.017). Therewas no significant correlation between CD44⁺/CD24^－/lowphenotype andthe other clinicopathological parameters, such as age, tumor size, TNMclassification, pathological type, histological grade, and so on(P＞0.05).The overall response of CD44⁺/CD24^－/lowpositive group was higher butwith no difference compared with CD44⁺/CD24^－/lownegative group (75%vs69.1%, P=0.542), and the rate of pathological complete remission (pCR)in CD44⁺/CD24^－/lowpositive group was higher than CD44⁺/CD24^－/lownegative group (38.9%vs18.2%, P=0.028).Conclusions:1. p73G4C14-to-A4T14polymorphisms are closelyassociated with the increased risk for TNBC in Chongqing women of HanNationality in China; GC/GC genotype is susceptible genotype for TNBCin Chongqing women of Han Nationality in China.2. CD44rs4756195polymorphisms are closely associated with the increased risk for breastcancer in Chongqing women of Han Nationality in China; AG and GGgenotype are susceptible genotype for breast cancer in Chongqing womenof Han Nationality in China.3. p73G4C14-to-A4T14polymorphisms aresignificantly associated with triple negative breast cancer, and the patients with breast cancer who carried with GC/GC genotype may have badprognosis.4. CD44rs4756195polymorphisms are closely associated withthe expression of CD44and axillary lymph nodes metastasis, the patientswith breast cancer who carried with GG genotype may have bad prognosis.5. p73G4C14-to-A4T14polymorphisms was not significantly associatedwith chemosensitivity for anthracyclines-based chemotherapy in breastcancer.6. CD44rs4756195polymorphisms are closely associated with theresponse to anthracyclines-based chemotherapy in breast cancer, and thepatients with breast who carried with A allelotype have higher the rate ofpCR. CD44rs4756195polymorphisms may be used as one of theindicators to evaluate the chemotherapeutic response of the patients withbreast cancer.7. CD44⁺/CD24^－/lowcells are demonstrated in certain breastcancer, CD44^＋/CD24^－/lowphenotype is associated with triple negativebreast cancer and the responsiveness of breast cancer toanthracycline-based chemotherapy. CD44^＋/CD24^－/lowphenotype may beused as one of the indicators to evaluate the clinical chemotherapeuticresponse of the patients with breast cancer...