Molecular and Cellular Biochemistry

, Volume 392, Issue 1–2, pp 273–280 | Cite as

Molecular insights into the association of obesity with breast cancer risk: relevance to xenobiotic metabolism and CpG island methylation of tumor suppressor genes

  • Shaik Mohammad Naushad
  • Tajamul Hussain
  • Omar S. Al-Attas
  • Aruna Prayaga
  • Raghunadha Rao Digumarti
  • Suryanarayana Raju Gottumukkala
  • Vijay Kumar KutalaEmail author


Obesity, genetic polymorphisms of xenobiotic metabolic pathway, hypermethylation of tumor suppressor genes, and hypomethylation of proapoptotic genes are known to be independent risk factors for breast cancer. The objective of this study is to evaluate the combined effect of these environmental, genetic, and epigenetic risk factors on the susceptibility to breast cancer. PCR–RFLP and multiplex PCR were used for the genetic analysis of six variants of xenobiotic metabolic pathway. Methylation-specific PCR was used for the epigenetic analysis of four genetic loci. Multifactor dimensionality reduction analysis revealed a significant interaction between the body mass index (BMI) and catechol-O-methyl transferase H108L variant alone or in combination with cytochrome P450 (CYP) 1A1m1 variant. Women with “Luminal A” breast cancer phenotype had higher BMI compared to other phenotypes and healthy controls. There was no association between the BMI and tumor grade. The post-menopausal obese women exhibited lower glutathione levels. BMI showed a positive association with the methylation of extracellular superoxide dismutase (r = 0.21, p < 0.05), Ras-association (RalGDS/AF-6) domain family member 1 (RASSF1A) (r = 0.31, p < 0.001), and breast cancer type 1 susceptibility protein (r = 0.19, p < 0.05); and inverse association with methylation of BNIP3 (r = −0.48, p < 0.0001). To conclude based on these results, obesity increases the breast cancer susceptibility by two possible mechanisms: (i) by interacting with xenobiotic genetic polymorphisms in inducing increased oxidative DNA damage and (ii) by altering the methylome of several tumor suppressor genes.


Obesity Cytochrome P450 1A1 Catechol-O-methyl transferase Ras-association (RalGDS/AF-6) domain family member 1 Breast cancer type 1 susceptibility protein BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Extracellular superoxide dismutase CpG island methylation 



This work was supported by the grant funded by Indian Council of Medical Research (ICMR), New Delhi (Ref No. 5/13/32/2007) and Prof. T. R. Rajagopalan Research Fund of SASTRA University, Thanjavur, India.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shaik Mohammad Naushad
    • 1
  • Tajamul Hussain
    • 2
  • Omar S. Al-Attas
    • 2
  • Aruna Prayaga
    • 3
  • Raghunadha Rao Digumarti
    • 4
  • Suryanarayana Raju Gottumukkala
    • 5
  • Vijay Kumar Kutala
    • 6
    Email author
  1. 1.School of Chemical & BiotechnologySASTRA UniversityThanjavurIndia
  2. 2.Center of Excellence in Biotechnology ResearchKing Saud UniversityRiyadhSaudi Arabia
  3. 3.Department of PathologyNizam’s Institute of Medical SciencesHyderabadIndia
  4. 4.Department of Medical OncologyNizam’s Institute of Medical SciencesHyderabadIndia
  5. 5.Department of Surgical OncologyNizam’s Institute of Medical SciencesHyderabadIndia
  6. 6.Department of Clinical Pharmacology & TherapeuticsNizam’s Institute of Medical SciencesHyderabadIndia

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