Huijts Petra E A, Vreeswijk Maaike P G, Kroeze-Jansema Karin H G, Jacobi Catharina E, Seynaeve Caroline, Krol-Warmerdam Elly M M, Wijers-Koster Pauline M, Blom Jannet C, Pooley Karen A, Klijn Jan G M, Tollenaar Rob A E M, Devilee Peter, van Asperen Christi J
Department of Clinical Genetics, K5-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Breast Cancer Res. 2007;9(6):R78. doi: 10.1186/bcr1793.
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.
最近发现五个基因组位点中的七个单核苷酸多态性(SNP)会使患乳腺癌的风险略有增加。
我们在一个未经选择的前瞻性队列中,对1267例连续的原发性乳腺癌患者进行了研究,调查了这些SNP的疾病特征与患者基因型之间的相关性。
与主要等位基因纯合子携带者相比,MAP3K1基因中SNP rs889312的杂合子携带者和次要等位基因纯合子携带者在乳腺癌诊断时淋巴结阳性的可能性较小(P = 0.044)。与主要等位基因纯合子携带者相比,TNCR9基因附近SNP rs3803662的杂合子携带者和次要等位基因纯合子携带者更有可能在60岁之前被诊断出患有乳腺癌(P = 0.025)。我们还注意到FGFR2中rs2981582的次要等位基因数量与患有乳腺癌和/或卵巢癌的一级和二级亲属的平均数量之间存在相关性(P = 0.05)。所有其他疾病特征,包括肿瘤大小和分级,以及雌激素或孕激素受体状态,均与这些变体中的任何一个无显著关联。
一些最近发现的与乳腺癌风险略有增加相关的基因组变体,也与乳腺癌特征或乳腺癌和卵巢癌家族史相关。这些发现为进一步研究这些低风险易感等位基因提供了有趣的新线索。