Abstract：
BRCA1-associated RING Domain 1 (BARD1) is an important gene related to breast cancer development. However, the role of BARD1 mutations in breast cancer remains inconclusive. This study is to investigate the relationship between exon mutations of BARD1 gene and the risk of early-onset breast cancer.
Totally, 60 cases of early-onset breast cancer patients (age 30-40 years) and 240 healthy women (age 30-40 years) were enrolled. Exon mutations of BARD1 were detected and analyzed by direct sequencing and SNaPshot.
The risk of breast cancer was increased by 3.475 times in carriers with deletion mutation at rs28997575 site of BARD1 (aOR1 = 3.475, 95%CI = 1.302-9.276) (p = 0.013). The risk of breast cancer in carriers with GC genotype at rs2229571 site of BARD1 was reduced by 72.6% (aOR1 = 0.274, 95%CI = 0.134-0.562) (p = 0.001), and that in carriers with CC genotype was reduced by 82.8% (aOR1 = 0.172, 95%CI = 0.076-0.392) (p = 0.001). After stratification with family history, the difference of rs2229571 site mutation genotype was statistically significant (OR = -2.169, 95%CI = 0.016-0.828, p = 0.032). Additionally, the frequency distribution of breast cancer family history in the case group (15%) was significantly more than that in the control group (6.7%) (p = 0.037).
The deletion mutation at rs28997575 locus of the BARD1 gene can significantly increase the risk of breast cancer. The mutation genotype of rs2229571 locus can significantly reduce the risk of breast cancer. Family history is associated with BARD1 gene polymorphism. A family history of breast cancer may be a risk factor for breast cancer.
Totally, 60 cases of early-onset breast cancer patients (age 30-40 years) and 240 healthy women (age 30-40 years) were enrolled. Exon mutations of BARD1 were detected and analyzed by direct sequencing and SNaPshot.
The risk of breast cancer was increased by 3.475 times in carriers with deletion mutation at rs28997575 site of BARD1 (aOR1 = 3.475, 95%CI = 1.302-9.276) (p = 0.013). The risk of breast cancer in carriers with GC genotype at rs2229571 site of BARD1 was reduced by 72.6% (aOR1 = 0.274, 95%CI = 0.134-0.562) (p = 0.001), and that in carriers with CC genotype was reduced by 82.8% (aOR1 = 0.172, 95%CI = 0.076-0.392) (p = 0.001). After stratification with family history, the difference of rs2229571 site mutation genotype was statistically significant (OR = -2.169, 95%CI = 0.016-0.828, p = 0.032). Additionally, the frequency distribution of breast cancer family history in the case group (15%) was significantly more than that in the control group (6.7%) (p = 0.037).
The deletion mutation at rs28997575 locus of the BARD1 gene can significantly increase the risk of breast cancer. The mutation genotype of rs2229571 locus can significantly reduce the risk of breast cancer. Family history is associated with BARD1 gene polymorphism. A family history of breast cancer may be a risk factor for breast cancer.
摘要：
BRCA1相关RING域1(BARD1)是与乳腺癌发生发展相关的重要基因。然而,BARD1突变在乳腺癌中的作用仍不确定.本研究旨在探讨BARD1基因外显子突变与早发性乳腺癌发病风险的关系。
完全正确,纳入60例早发性乳腺癌患者（年龄30-40岁）和240例健康女性（年龄30-40岁）。通过直接测序和SNaPshot检测并分析BARD1的外显子突变。
BARD1rs28997575位点缺失突变携带者患乳腺癌的风险增加了3.475倍（aOR1=3.475，95CI=1.302-9.276）（p=0.013）。在BARD1的rs2229571位点具有GC基因型的携带者患乳腺癌的风险降低了72.6％（aOR1=0.274，95CI=0.134-0.562）（p=0.001），在具有CC基因型的携带者中，减少了82.8％（aOR1=0.172，95CI=0.076-0.392）（p=0.001）。在与家族史分层后，rs2229571位点突变基因型差异有统计学意义(OR=-2.169,95CI=0.016～0.828,p=0.032)。此外,病例组乳腺癌家族史的频率分布（15％）明显多于对照组（6.7％）（p=0.037）。
BARD1基因rs28997575位点的缺失突变可显著增加患乳腺癌的风险。rs2229571位点的突变基因型可以显著降低乳腺癌的发病风险。家族史与BARD1基因多态性有关。乳腺癌家族史可能是乳腺癌的危险因素。
完全正确,纳入60例早发性乳腺癌患者（年龄30-40岁）和240例健康女性（年龄30-40岁）。通过直接测序和SNaPshot检测并分析BARD1的外显子突变。
BARD1rs28997575位点缺失突变携带者患乳腺癌的风险增加了3.475倍（aOR1=3.475，95CI=1.302-9.276）（p=0.013）。在BARD1的rs2229571位点具有GC基因型的携带者患乳腺癌的风险降低了72.6％（aOR1=0.274，95CI=0.134-0.562）（p=0.001），在具有CC基因型的携带者中，减少了82.8％（aOR1=0.172，95CI=0.076-0.392）（p=0.001）。在与家族史分层后，rs2229571位点突变基因型差异有统计学意义(OR=-2.169,95CI=0.016～0.828,p=0.032)。此外,病例组乳腺癌家族史的频率分布（15％）明显多于对照组（6.7％）（p=0.037）。
BARD1基因rs28997575位点的缺失突变可显著增加患乳腺癌的风险。rs2229571位点的突变基因型可以显著降低乳腺癌的发病风险。家族史与BARD1基因多态性有关。乳腺癌家族史可能是乳腺癌的危险因素。
