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  • br Material and Methods br Results br Discussion

    2018-11-14


    Material and Methods
    Results
    Discussion Here we describe a central tumor-promoting role for CPSF6 in luminal B, HER2-overexrepressing and TNBC subtypes associated with poor patient outcome. CPSF6 was found to be part of the pan-cancer pro-oncogenic A-to-I RNA editing machinery through interaction with paraspeckles nuclear subdomain involved in retention of A-to-I RNA edited molecules as well as ADAR1 enzyme thus influencing A-to-I RNA editing process and tumorigenesis (Fig. 8).
    Conflicts of Interest
    Authors\' Contributions
    Acknowledgements
    J.J. Lebrun is the recipient of the McGill Sir William Dawson Research Chair. This work was supported by the Canadian Institutes of Health Research (operating grants #233437 and 233438) granted to Suhad Ali.
    Background Breast cancer is the most common cancer in women with a high prevalence in economically developed countries (Kristensen et al., 2014; Parkin et al., 2005). The etiology of breast cancer is multifactorial. Age, genetic mutations and life-time purchase l-ascorbic acid exposure are well known risk factors (Gail and Pfeiffer, 2015; Petracci et al., 2011; Pfeiffer et al., 2013). These factors explain only a small part of the etiology (Turnbull and Rahman, 2008) suggesting that environmental factors may also be relevant in the development of breast cancer (Bonefeld-Jorgensen et al., 2011; Coyle, 2004). A change in the topological distribution of mammary carcinoma since 1975 (Bright et al., 2016; Darbre, 2016, 2009, 2005, 2003) towards an higher incidence in the upper outer quadrant seems to point to underarm cosmetic products (UCPs) as a potential contributor (Darbre, 2009, 2005, 2003; Darbre et al., 2013b). Previous studies investigating the effect of UCPs on breast cancer have shown conflicting results (McGrath, 2003; Mirick et al., 2002; Pasha et al., 2008; Rodrigues-Peres et al., 2013). Therefore, latest systematic reviews were not able to provide conclusive evidence (Namer et al., 2008; Willhite et al., 2014). Active ingredients in most UCPs are aluminum-based compounds as aluminum chloride and aluminum chlorohydrate. Aluminum salts have been associated with oxidative stress, DNA double strand breaks, proliferation, interference in estrogen action before (Darbre, 2009; Darbre et al., 2013a; Dyrssen et al., 1987; Farasani and Darbre, 2015; Lankoff et al., 2006; Sappino et al., 2012) and with metastasis recently (Mandriota et al., 2016). Mandriota et al. (2016a) demonstrated in an established cancer mouse model that concentrations of aluminum in the range of those measured in human breast are able to transform cultured mammary epithelial cells, enabling them to form tumors and to metastasize. It was further suggested that frequent use of UCPs containing aluminum salts is a main source of measured aluminum in breast structures (Darbre et al., 2013b, 2011; Exley et al., 2007; Mannello et al., 2009). Due to the genotoxic and possibly carcinogenic effect of aluminum salts, the use of UCPs may be related to breast cancer (Darbre, 2001; Jennrich and Schulte-Uebbing, 2016; Pineau et al., 2014; Rodrigues-Peres et al., 2013; Sappino et al., 2012). The relationship of UCPs containing aluminum salts with breast cancer was investigated in few epidemiological studies showing conflicting results (Fakri, 2006; McGrath, 2003; Mirick et al., 2002). Mirick et al. (2002) and Fakri (2006) found no significant associations between antiperspirants and increased risk of breast cancer. In contrast, McGrath (2003) found that patients using UCPs frequently received their breast cancer diagnosis at an earlier age than patients avoiding UCPs. However, none of these studies included breast tissue measurements of aluminum with regard to UCP use. There exists, so far, no controlled study investigating the relationship of aluminum with breast cancer combining an epidemiologic approach with breast tissue measurements.
    Methods
    Results A total of 460 women participated in this study, of these 210 were breast cancer cases and 250 were healthy controls. We excluded one case due to breast cancer diagnosis earlier than 5years before the interview. One control had to be excluded due to unclear breast tissue pathology. Finally, 209 cases were matched 1:1 to 209 controls minimizing the age differences within pairs to a maximum of 3.5years. Consequently cases and controls did not differ regarding mean age (51.9±12.0 versus 51.8±12.1). Tissue samples were available in 100 cases and 52 controls undergoing surgery.