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  • The classical approach for the assessment of an environmenta

    2018-11-07

    The classical approach for the assessment of an environmental carcinogen consists of both experimental and epidemiological investigations. On the experimental front, existing studies have focused on the effects of aluminium on cultured mammary epithelial cells. Concentrations of aluminium in the range of those measured in the human breast transform MCF-10A human mammary epithelial cytotoxicity and NMuMG mouse mammary epithelial cells after several weeks of culture. In MCF-10A cells, these effects were preceded by the induction of DNA double strand breaks (DSB), of which the repair is often intrinsically mutagenic, and were not reversible following aluminium withdrawal from the culture medium, thus suggesting a genetic modification of the cells. Consistent with this hypothesis, mammary epithelial cells cultured in the presence of aluminium accumulate mutations (; and our unpublished data). However, it is still unclear whether aluminium is a true mutagen, or if it selects for mutations already present in the mammary epithelial cell lines. When injected into NOD-SCID or nude mice, NMuMG cells transformed by aluminium form tumors and metastasis, whereas untreated controls do not (). In other studies, aluminium increased the migratory and invasive properties of MCF-7 or MDA-MB-231 human breast cancer cells (). As it is true for other metals and known carcinogens, aluminium is not detectably mutagenic in bacteria (). Altogether, these results support the hypothesis that aluminium is an environmental breast carcinogen. Epigenetic effects might contribute to aluminium-induced cellular transformation. On the epidemiological front, studies investigating the link between aluminium and BC have led to conflicting results. In a retrospective study using the data from 437 BC patients, reported that frequency of antiperspirant/deodorant (collectively referred to as UCP: underarm cosmetic product) use, in combination with underarm shaving, was associated with a BC diagnosis at an earlier age. The effect was particularly marked in women who started UCP use before the age of 16. In another retrospective study, using the data of 813 BC patients, found no association between UCP use and BC risk. The latter study did not collect information on frequency or age of use. Neither study measured the levels of aluminium in the breasts of cancer cases or controls. In this issue of , a new retrospective study () analyzing the data from 209 BC cases and 209 healthy controls, revealed an association between self-reported UCP use and BC risk. The association was statistically significant for patients who reported using UCP more than once a day when they were under the age of 30. Importantly, this study also measured the aluminium content of a large subsample of BC cases and controls, and found that self-reported UCP use correlates with higher aluminium content in the breast. It is worth highlighting that the concentrations of aluminium measured in BC cases are in the range of those that transform mammary epithelial cells ().
    A review by Gristina et al. () examined in detail the association between cancer cytotoxicity and diabetes, confirming that type 2 diabetes (T2DM) and insulin resistant states are associated with an increased risk of several cancers. Similarly, a meta-analysis of 19 studies, both cross-sectional and prospective, showed a positive association between serum glucose and risk of cancer (). Obesity, particularly abdominal obesity, is a common risk factor for both cancer and T2DM, as are age, ‘poor diet’, physical inactivity, smoking and alcohol consumption thus these risk factors are potential confounders of associations between glucose and cancer risk. In contrast to the previous associations observed between impaired glucose regulation and cancer risk, the recent study by Falk et al. (), in this edition of , has shown that in healthy middle-aged men, low blood glucose concentrations in the first 10min of an intravenous glucose tolerance test, but not fasting glucose or values later during the IVGTT, were associated with the development of cancer over the subsequent 40years of follow-up. These men at increased risk of cancer had no evidence of impaired glucose regulation. The association was independent of age, fasting glucose, smoking, physical fitness, body weight and height, although no measures of diet or alcohol use were available.