Panigoro Sonar Soni, Listiyaningsih Erlin, Nurlaila Ika, Mahesworo Bharuno, Hidayat Alam Ahmad, Budiarto Arif, Sudigyo Digdo, Amirullah Dian, Simon Simon, Baurley James, Pardamean Bens
Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
Genetics Indonesia, Jakarta, 12940, Indonesia.
Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3985-3991. doi: 10.31557/APJCP.2021.22.12.3985.
Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population.
DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression.
There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population.
Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.
近期多项研究表明，乳腺癌（BC）患者发病年龄呈现出向低龄化大幅转变的趋势。然而，这些研究相对局限于白种人群体。这项初步研究旨在调查印度尼西亚年轻BC患者的遗传风险因素。
从79例年龄小于40岁的BC患者和90例健康样本中提取DNA样本。使用Illumina NextSeq 500平台对这些DNA样本进行测序，并进行预处理以提取单核苷酸多态性（SNP）数据。首先，进行多个单变量逻辑回归分析，以检验每个SNP与年轻患者BC发病率之间的关联。此外，为了分析多个SNP产生的多基因效应，我们采用了多变量逻辑回归。
仅有15个SNP通过了我们95%的检出率阈值，随后用于关联测试。其中一个变体rs3219493与早发性BC显著相关（p值 = 0.025，OR = 3.750，95% CI = 1.178 - 11.938）。这一结果与多变量逻辑回归模型一致，在该模型中发现该相关变体具有统计学意义（p值 = 0.008，OR = 8.398，95% CI = 1.720 - 40.920）。该变体被鉴定为MUTYH基因内的内含子变体，在多项已发表的研究中报道，其在中国、意大利和西班牙裔犹太人群体中与乳腺癌发病率相关。然而，在印度尼西亚人群中，尚无证据表明该基因会影响早发性BC的发病风险。
尽管本初步研究在分析样本量方面存在局限性，但我们发现内含子MUTHY与印度尼西亚早发性BC显著相关，这为基于人群独特方面的深入研究以及化疗进展提供了更广阔的视角。
