RT Journal Article
SR Electronic
T1 Germline genetics encode the resistance, risk, and lymphatic metastasis of triple-negative breast cancer in the southern Chinese population
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 302398
DO 10.1101/302398
A1 Mei Yang
A1 Yanhui Fan
A1 Qiangzu Zhang
A1 Shunhua Han
A1 Xiaoling Li
A1 Teng Zhu
A1 Minyi Cheng
A1 Juntao Xu
A1 Ciqiu Yang
A1 Hongfei Gao
A1 Chunming Zhang
A1 Michael Q. Zhang
A1 You-Qiang Song
A1 Gang Niu
A1 Kun Wang
YR 2018
UL http://biorxiv.org/content/early/2018/04/16/302398.abstract
AB BACKGROUND Triple-negative breast cancer (TNBC) patients generally have poor prognosis but could be led to a better outcome if the risk can be identified in the stage without symptoms. Previously, determining the hereditary risk relied solely on assessing the potential damage due to single mutations or individually damaged genes, which has led to fragmentation in our understanding of genetic risk, particularly when multiple factors are involved. It is currently difficult to obtain a complete picture of genetic risk that unites individual discoveries under a single theoretical frame, not to mention a category method for systematically assessing all individuals within a population.METHODS We postulated that there is a persistent stress from certain deterministic pathogenic factors on the whole population, so that we can simply solve this problem by assessing the innate stress resistance in each individual. This stress resistance is encoded in germline DNA and can be disrupted by rare mutations in certain genes. We developed a method to statistically infer whether a set of cancer related pathways in individual subjects would be differentially active or repressed driven by all currently mutated genes.RESULTS We divided all 141 subjects including 29 TNBC patients and 112 normal females from Southern China into five categories of TNBC risk: very high risk, high risk, average, low risk, and zero risk. Approximately 4.5% and 31% were evaluated to be at very high risk of TNBC in normal population and patients, respectively. Whereas around 25% would have zero risk of TNBC in normal population. Surprisingly, lymphatic metastasis correlated with the risk of disease (r2 = 0.99, p = 0.0035) in patient population.CONCLUSIONS Our findings suggested that a health human genome could encode an ability fully protecting the individual from a persistent neoplastic threat.