Lehrer Steven, Rheinstein Peter H
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York.
Severn Health Solutions, Severna Park, Maryland.
medRxiv. 2024 Jul 9:2024.07.08.24310089. doi: 10.1101/2024.07.08.24310089.
Tall women are more likely to develop breast cancer (BC). High Mobility Group AT-Hook 1(HMGA1), an oncofetal protein, plays a role in the progression of breast cancer. Non-coding sequences proximal to HMGA1 contain variants associated with 4.83 cm taller height. In the current study, we used UK Biobank data to examine the relationship of HMGA1 to height, risk, and prognosis of women with breast cancer.
Our analysis included all subjects with invasive BC that occurred either before or after participant enrollment and were recorded in the UK Biobank database using self-reported data and the International Classification of Diseases (ICD10, ICD9). We divided the subjects into three previously described three height groups: Short (< 155 cm), Medium (155 cm to 175 cm), Tall (> 175 cm). We analyzed the HMGA1 SNP rs41269028, a single nucleotide intron variant, C > T, minor allele frequency 0.044. SNP rs41269028 was previously evaluated in subjects with diabetes.
Height of 9583 women with BC homozygous for the HMGA1 SNP rs41269028 major allele was 162.29 cm ± 6.18. Height of 944 women with BC who were carriers or homozygotes (CT + TT) of the minor allele T was 162.88 cm ± 6.001. This difference was significant (p = 0.005). The effect of height group on survival was significant (p = 0.032, log rank test). Tall women had the poorest survival. The effect of HMGA1 SNP rs41269028 genotype on BC risk (p = 0.602) and survival (p = 0.439, log rank test) was insignificant.
We conclude that HMGA1 influences height, but we were unable to demonstrate that HMGA1 is related to increased incidence or poor prognosis of tall women with breast cancer. We did find that tall women with breast cancer have poorer survival than short women. Our finding that tall women have a worse prognosis is important because it could help the oncologist decide, along with other prognostic factors, whether adjuvant therapy is warranted.
身材较高的女性患乳腺癌(BC)的可能性更大。高迁移率族AT-钩蛋白1(HMGA1)是一种癌胚蛋白,在乳腺癌进展中起作用。HMGA1附近的非编码序列包含与身高高4.83厘米相关的变异。在本研究中,我们使用英国生物银行的数据来研究HMGA1与乳腺癌女性的身高、风险和预后之间的关系。
我们的分析包括所有在参与者入组之前或之后发生侵袭性BC的受试者,并使用自我报告数据和国际疾病分类(ICD10、ICD9)记录在英国生物银行数据库中。我们将受试者分为先前描述的三个身高组:矮(<155厘米)、中(155厘米至175厘米)、高(>175厘米)。我们分析了HMGA1单核苷酸多态性(SNP)rs41269028,这是一个单核苷酸内含子变异,C>T,次要等位基因频率为0.044。SNP rs41269028先前已在糖尿病受试者中进行过评估。
9583名携带HMGA1 SNP rs41269028主要等位基因纯合子的乳腺癌女性的身高为162.29厘米±6.18厘米。944名携带次要等位基因T的杂合子或纯合子(CT+TT)的乳腺癌女性的身高为162.88厘米±6.001厘米。这种差异具有统计学意义(p=0.005)。身高组对生存率的影响具有统计学意义(p=0.032,对数秩检验)。身材较高的女性生存率最差。HMGA1 SNP rs41269028基因型对乳腺癌风险(p=0.602)和生存率(p=0.439,对数秩检验)的影响不显著。
我们得出结论,HMGA1影响身高,但我们无法证明HMGA1与身材较高的乳腺癌女性的发病率增加或预后不良有关。我们确实发现,患有乳腺癌的身材较高的女性比身材矮小女性的生存率更差。我们发现身材较高的女性预后较差这一结果很重要,因为它可以帮助肿瘤学家结合其他预后因素来决定是否需要辅助治疗。