Differences in aluminum concentration between
Differences in aluminum concentration between cases and controls were only evident when restricting the analysis to cases with tumors in the upper outer quadrant, supporting the hypothesis of Darbre (2005, Darbre, 2009) that tumors in the upper outer quadrant are affected by the use of UCPs. Results of the questionnaire part, however, do not support this hypothesis. Self-reported UCP use did not differ significantly between cases and controls when considering tumor localization. Tissue samples of controls showed less variation in aluminum concentrations than samples of breast cancer patients. In ten breast cancer patients, aluminum concentrations over 60nmol/g up to 367nmol/g dry weight (15–115nmol/g wet weight) were observed. Mandriota et al. (2016) and colleges recently showed that aluminum salt concentrations of 100nmol/g wet weight lead to transformation of in-vitro cultured mammary epithelial gnrh agonists enabling them to form tumors and metastasis in mouse models. In contrast, aluminum concentration in controls reached a maximum of 24.5nmol/g dry weight (8nmol/g wet weight) only. Our study has several strengths. We combined comprehensive questionnaire data of breast cancer cases and healthy individuals on underarm hygiene habits with data of aluminum concentration in tissue samples. We applied a well-developed and accurate method for aluminum measurement (Exley et al., 2007; House et al., 2013). A standardized sampling procedure, high purity of reagents and a high measurement accuracy minimized background contamination. It is likely that aluminum in breast tissue has a patchy distribution (Exley et al., 2007; House et al., 2013), therefore, we collected multiple tissue samples alongside the transect from upper outer to upper inner quadrant. Certain limitations of our study need to be discussed. A case-control study is susceptible to recall bias. Self-reporting information may be incomplete or inaccurate and may differ between cases and controls. Younger women may remember in more detail about their specific hygiene habits than elderly women. The mix of incident and prevalent cases in our study may be an additional source of bias. We assessed whether the time span between BC diagnosis and interview date is an effect modifier for the relation of UCP use with risk for BC. Although there is no significant effect modification of the different timing of interviews (p=0.282, for the ‘UCP use under the age of 30’ model, p=0.877 for the ‘UCP use in the last 5 years’ model) we cannot rule out any recall issues between incident and prevalent cases. We tried to reduce reporting and measurement bias by performing personal interviews with well-trained interviewers. The limited sample size of the study leads to relatively small numbers in the sub-categories of the main exposure variable. Though significant, the result concerning UCP use several times per day is based on a few cases only. Furthermore, we cannot exclude a reverse causation effect, meaning Retroposon the breast tumor may accumulate aluminum. There are studies that reported higher levels of transition metals in tissue of breast cancer patients (Cui et al., 2007; Ionescu et al., 2006; Romanowicz-Makowska et al., 2011). Although, we matched cases and controls on age, the subgroup for tissue sampling is not age matched. However, in our study, aluminum concentrations did not correlate with age (r=−0.028, p=0.7291). In conclusion, our study provides novel insights and additional evidence regarding a possible role of UCP use and aluminum salts in the etiology of breast cancer. Our findings suggest that frequent use of UCPs may lead to an accumulation of aluminum in breast tissue. We could show that women who reported to use UCPs several times a day starting at an age under 30years may even have an increased risk for breast cancer. Until definitive answers about the involvement of aluminum in carcinogenesis of breast cancer, we recommend that particularly women at their younger ages should be careful with the use of UCPs and avoid its excessive use.