Familial diabetes is associated with reduced risk of cancer in diabetic patients: a possible role for metformin.

Type 2 diabetes mellitus (DM2) is a risk factor of a number of malignancies. Therefore, it is important to identify factors linking DM2 and cancer within family units and how current treatment regimens influence the development of cancer in DM2 patients. The present case-controlled study was designed to assess DM2 prevalence among parents or siblings of (a) cancer patients who did not have diabetes (n = 77; age 59.3 ± 1.3 years) or (b) had overt (n = 197; 63.7 ± 0.6 years) or latent (n = 25; 61.5 ± 1.5 years) DM2 and (c) of female DM2 patients without cancer (n = 172; 61.7 ± 0.6 years). In the families of cancer-free DM2 women, DM2 was found to be significantly more frequent (30.8 ± 3.5%) than in families of cancer patients without diabetes (in all patients: 6.5 ± 2.8%; in female patients: 5.0 ± 3.4%). More importantly, DM2 in families of cancer-free DM2 women was more frequent than in the families of DM2 patients having mammary (9.5 ± 4.5%), endometrial (6.3 ± 4.1%) or any other cancer (in all: 15.2 ± 2.6%; in women: 12.9 ± 2.8%). Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2. Our data indicate that familial DM2 may have a protective effect for some cancer types and that the type of anti-diabetes therapy may be a factor of influence in the associations observed.