Molecular Profiling of Breast Cancer Susceptibility of Obese or Insulin-Resistant and Pre-Diabetic Patients Using ITLN1 and CD295 SNPs

Abstract

AbstractMutations in cluster of differentiation (CD) 295 gene, encoding class I cytokine receptor, are associated with obesity and breast cancer (BC). SNPs in the adipocyte-inferred novel cytokine intelectin 1 (ITLN1) remain understudied in connection to CD295 polymorphisms and diabetes mellitus (DM) or a pre-diabetic state, as well as to DNA damage seen in BC. We will explore whether CD295 (ID rs6700896) and ITLN1 (rs rs952804) SNPs impact BC with or without DM, insulin resistance (IR) or obesity. Effects of ITLN1 or CD295 polymorphism(s) on DNA damage in BC were also examined. Blood samples from 170 women with BC (including 33 and 48 with DM and pre-diabetes, respectively) and from 108 age-matched women in the control group were collected. Plasma insulin, leptin, CD295, and ITLN1 levels were measured by ELISA. DNA damage was assessed using an alkaline comet assay.BC cases with clinical stage T II and positive LN as well as tumor histologic grade III, presence of obesity, pre-diabetic events, DM or IR were associated with CD295 rs6700986 mutant homozygous (CC) and heterozygous (CT) genotype and ITLN1 rs952804 mutant heterozygous genotype (CT) (P ≤ 0.05). Tail DNA (%) and tail moment units were significantly associated with CD295 rs6700986 CT and ITLN1 rs952804 TT genotypes. C allele (CT+CC vs. TT) and T allele (TT+CT vs. CC) for CD295 rs6700986 and ITLN1 rs952804, respectively, were associated with BC risk (P ≤ 0.05). ITLN1 (rs952804) and CD295 (rs6700986) SNPs should be considered as BC associated-susceptibility risk factors in obese, insulin resistant, or pre-diabetics.Graphical AbstractRemarks/HighlightsITLN1 and CD295 polymorphism testing might be utilized for accessing BC susceptibility in either obese or insulin resistant, pre-diabetic patients.A modestly increased risk of BC in women harboring the C allele of CD295 rs6700986 polymorphism and the T allele of the ITLN1 rs952804, where:Tumor clinical stage T II and positive LN involvement as well as the tumor histologic grade III, obesity existence, pre-diabetic event and being diabetic as well as IR cases were associated with CD295 rs6700986 mutant homozygous (CC) and heterozygous (CT) genotype and ITLN1 rs952804 mutant heterozygous cases (CT) (P ≤ 0.05).Tail DNA (%) and tail moment unit were significantly associated with CD295 rs6700986 CT genotype and ITLN1 rs952804 TT. These SNPs could be considered as BC associated risk factor.In dominant effect of the C allele (CT+CC vs TT) and the T allele (TT+CT vs CC) for CD295 rs6700986 and ITLN1 rs952804, respectively, were associated with BC events and risk (P ≤ 0.05).CD295 rs6700986 and ITLN1 rs952804 SNPs may be considered BC-associated risk for G3, T2, +LN, obesity, pre-diabetic/diabetic and IR in BC patients.