The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13-1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07-1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99-1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

The controversial relationship between benign thyroid diseases and breast cancer (BC) has been investigated for over 50 years. Despite extensive population studies, the results as a whole have been inconsistent. The purpose of this study was to collate and analyse available data, calculating a pooled odds ratio (OR) of the risk of BC in patients diagnosed with benign thyroid diseases. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Inclusion criteria required a confirmed diagnosis of a benign thyroid disease, reporting of an OR or data to calculate an OR (and 95% confidence interval, CI) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled OR calculated. 28 studies were included in the meta-analysis. There was significant evidence of an increased risk of BC in patients with autoimmune thyroiditis, evident in a pooled OR 2.92 (95% CI 2.13-4.01). In addition, the results supported an increased risk associated with the presence of anti-thyroid antibodies (OR 2.02, 95% CI 1.63-2.50) and goitre (OR 2.26, 95% CI 1.39-3.69). Subgroup analysis of antibody presence revealed increased risk associated with both anti-TPO (OR 2.64, 95% CI 1.82-3.83) and anti-TG (2.71, 95% CI 1.58-4.69). Quantitative analysis of hypothyroidism and hyperthyroidism was not significant. While these results indicate an association between thyroid auto-immunity and BC, further prospective studies are required to definitively prove causality.

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