Unraveling the Genetic Links Between Obesity or Insulin-Resistance and Breast Cancer through the Impact of CD295 and ITLN1 SNPs with DNA Damage in a Case-Controlled Study with Bioinformatics Analysis #

Nadia M Hamdy^1*Yasser O. Mosaad^2,3Reham Elshimy⁴Ahmed A Hady⁵Queran Lin⁶Zayd Jastaniah⁷Razan Amjad⁷Huda Altoukhi⁷Hatim Almarzouki⁷Dr. med. Ahmed Abdelsamad. MD. M.Sc. MHBA⁸Hekmat M El Magdoub⁹Doaa Fathi¹⁰

• ¹Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
• ²Future University in Egypt, New Cairo City, Egypt
• ³Faculty of Pharmacy, New Cairo, Egypt
• ⁴National Cancer Institute, Cairo, Egypt
• ⁵Mansoura University Faculty of Medicine, Mansoura, Egypt
• ⁶Imperial College London Institute of Global Health Innovation, London, United Kingdom
• ⁷King Abdulaziz University Faculty of Medicine, Jeddah, Saudi Arabia
• ⁸Klinikum Vest GmbH Behandlungszentrum Knappschaftskrankenhaus Recklinghausen, Recklinghausen, Germany
• ⁹Misr International University Faculty of Pharmacy, Cairo, Egypt
• ¹⁰Alexandria University Faculty of Pharmacy, Alexandria, Egypt

Background: Mutations in the 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. Aim: To explore whether CD295 (rs6700986) and ITLN1 (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. All of these to be confirmed by bioinformatics/in silico analysis. Subjects and Methods: 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. rs6700986 and rs952804 were analyzed by RT-PCR. DNA damage was assessed using alkaline comet assay. Results: 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) genotypes and ITLN1 rs952804 mutant heterozygous (CT) genotype (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). Conclusion: CD295 (rs6700986) and ITLN1 (rs952804) SNPs to be considered as BC associated-susceptibility risk factors in obese, insulin-resistant or pre-diabetics.