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  • br tiple hypothesis testing has generally been the case in

    2020-08-14


    tiple Actinomycin D testing has generally been the case in studies similar to this study,26,46,47 proposing possible
    application of results without such considerations. Fifth, the adjusted covariates may not all be confounders but rather mediators, or simply just associated with either the outcome variable or other covariates. Including all covari-ates in multivariate analysis may result in over-adjust-ment. Thus, sensitivity analyses were performed, including and excluding covariates that did not meet the definition of confounding in the multivariate model, but resulting changes were minimal.
    CONCLUSIONS
    The current study suggests that modifiable health behav-iors may be associated with an FHCA, and that this asso-ciation may differ by sex. In general, males with an FHCA showed better health behaviors, whereas females with an FHCA showed worse.
    Health behaviors are important modifiable risk factors of cancer, and may be associated with an FHCA. To identify whether health behaviors of those with an FHCA have changed because of the effect of FHCA, or whether an FHCA did not influence such health behav-iors, further prospective research is needed.
    ACKNOWLEDGMENTS
    Data for the present study were provided from the Korean Genome Analysis Project (4845-301), the Korean Genome and
    The present study was supported by a research grant in 2017 by the Korean Foundation for Cancer Research, Seoul, Republic of Korea.
    No financial disclosures were reported by the authors of this paper.
    SUPPLEMENTAL MATERIAL
    REFERENCES
    8. Finney LJ, Iannotti RJ. The impact of family history of breast cancer on women’s health beliefs, salience of breast cancer family history,
    12. Shah M, Zhu K, Palmer RC, Jatoi I, Shriver C, Wu H. Breast, colorec-tal, and skin cancer screening practices and family history of cancer in 
    25. Huang XE, Tajima K, Hamajima N, et al. Comparison of lifestyle and risk factors among Japanese with and without gastric cancer family
    www.ajpmonline.org
    35. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal. NCCN guideline.www.nccn.org/professionals/ physician_gls/default.aspx#detection. Published 2018. Accessed Octo-ber 10, 2018. 36. Zlot AI, Silvey K, Newell N, Coates RJ, Leman R. Family history of colorectal cancer: clinicians’ preventive recommendations and patient behavior. Prev Chronic Dis. 2012;9:E21.
    37. Zlot A, Cox S, Silvey K, Leman R. The effect of chronic disease family
    Contents lists available at ScienceDirect
    Biomedicine & Pharmacotherapy
    journal homepage: www.elsevier.com/locate/biopha
    Association between histone lysine methyltransferase KMT2C mutation and T clinicopathological factors in breast cancer
    Xiaoqing Chena,b,1, Guochun Zhangb,1, Bo Chenb,1, Yulei Wangb, Liping Guoa,b, Li Caob, Chongyang Renb, Lingzhu Wenb, Ning Liaoa,b,c, a The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China b Department of Breast Cancer, Guangdong provincal people’s Hospital & Guangdong, Academy of Medical Sciences, Guangzhou, China c School of Medicine, South China University of Technology, Guangzhou, China
    Keywords:
    Breast cancer
    Epigenetics
    KMT2C mutation
    Next-generation sequencing technique 
    As an important regulator of epigenetics, histone lysine methyltransferase 2C (KMT2C), is frequently mutated in multiple human cancers and is considered to be crucial for the occurrence and development of numerous can-cers. However, the relationship between KMT2C mutation and clinicopathological characteristics in patients with breast cancer is unclear. In the present study, we performed next-generation sequencing to investigate the mutation status of KMT2C in 411 treatment-naive Chinese patients with breast cancer at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those of patients with breast cancer from The Cancer Genome Atlas (TCGA, n = 981) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1454) cohorts. The KMT2C mutation rate was 8.0% (33/411) in the GDPH cohort, whereas that in the TCGA and the METABRIC cohorts was 7.0% (69/981) and 14.5% (211/1454), respectively. Nineteen novel mutations were observed in the GDPH cohort. KMT2C mutations were found to be significantly associated with patients older than 50 years (GDPH: p = 0.007; TCGA: p = 0.005; METABRIC: p = 0.015). The KMT2C mutation rate in HR+/HER2- breast cancer patients was higher than that in the other subtypes (GDPH: p = 0.047; TCGA: p = 0.032; METABRIC: p = 0.046). In addition, KMT2C mutations in the GDPH cohort were observed in invasive lobular breast cancer (ILC) at 30.8% (4/13). Further, KMT2C mutation was not found to be an independent risk factor in the prognosis of patients with breast cancer [TCGA: hazard ratio (HR), 1.71; 95% confidence interval (CI), 0.88–3.31; p = 0.111; METABRIC: HR, 2.03; 95% CI, 0.45–3.08; p = 0.419]. This is the first study to preliminarily elucidate the role of KMT2C mutations in Chinese patients with breast cancer and further identified significant KMT2C mutation differences according to race and ethnicity. KMT2C might be a susceptibility gene of Chinese patients with ILC that would help define high-risk groups that could benefit from adapted, personalized screening strategies.