Association of genetic variants at TOX3, 2q35 and 8q24 with the risk of familial and early-onset breast cancer in a South-American population.

Recent Genome-Wide Association Studies have identified several single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) among women of Asian, European, and African-American ancestry. Nevertheless, the contribution of these variants in the South American population is unknown. Furthermore, there is little information about the effect of these risk alleles in women with early BC diagnosis. In the present study, we evaluated the association between rs3803662 (TOX3, also known as TNRC9), rs13387042 (2q35), and rs13281615 (8q24) with BC risk in 344 Chilean BRCA1/2-negative BC cases and in 801 controls. Two SNPs, rs3803662 and rs13387042, were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC. The risk of BC increased in a dose-dependent manner with the number of risk alleles (P-trend < 0.0001 and 0.0091, respectively). The odds ratios for BC in familial BC and in early-onset non-familial BC were 3.76 (95%CI 1.02-13.84, P = 0.046) and 8.0 (95%CI 2.20-29.04, P = 0.002), respectively, for the maximum versus minimum number of risk alleles. These results indicate an additive effect of the TOX3 rs3803662 and 2q35 rs13387042 alleles for BC risk. We also evaluated the interaction between rs3803662 and rs13387042 SNPs. We observed an additive interaction only in non-familial early-onset BC cases (AP = 0.72 (0.28-1.16), P = 0.001). No significant association was observed for rs13281615 (8q24) with BC risk in women from the Chilean population. The strongly increased risk associated with the combination of low-penetrance risk alleles supports the polygenic inheritance model of BC.

Relationship between Apolipoprotein E polymorphism and nephropathy in type-2 diabetic patients.

Twenty to forty percent of type-2 diabetic patients (DM2) present nephropathy. Genetic polymorphism of Apolipoprotein E (Apo E) has been proposed as a risk factor in the development and progression of diabetic nephropathy. The purpose of the study was to evaluate the relationship between Apo E polymorphism and presence of nephropathy in DM2 patients. We studied 85 DM2 patients with a similar nutritional state, environmental and socioeconomic condition and more than 10 years of evolution. They were grouped in DM2 patients with kidney complications (n=56) and without kidney complications (n=29; control group). Apo E genotype was determined by restriction fragment-length polymorphism analysis. A plasmatic biochemical characterization was performed on all the subjects studied. The 85 DM2 patients had arterial hypertension in treatment. The nephropathy diabetic group showed differences (p<0.001) in BMI, systolic blood pressure, glycemia, cholesterol (total, HDL and LDL), HbA1c and creatinine. The e4 allelic frequency was 8% in the nephropathy group versus 25.9% in the control group. Apo e3 allele and E3/3 genotype frequency were higher and E3/4 genotype was lower in the nephropathy group than in controls. These groups also showed differences in total, HDL and LDL cholesterol. DM2 patients without nephropathy presented a higher frequency of e4 allele. These results could suggest a protective role of e4 allele in the development and progression of diabetic nephropathy.