PLoS ONE (Jan 2014)

Mitochondrial control region alterations and breast cancer risk: a study in South Indian population.

  • Nageswara Rao Tipirisetti,
  • Suresh Govatati,
  • Priyanka Pullari,
  • Sravanthi Malempati,
  • Murali Krishna Thupurani,
  • Shyam Perugu,
  • Praveen Guruvaiah,
  • Lakshmi Rao K,
  • Raghunadha Rao Digumarti,
  • Varadacharyulu Nallanchakravarthula,
  • Manjula Bhanoori,
  • Vishnupriya Satti

DOI
https://doi.org/10.1371/journal.pone.0085363
Journal volume & issue
Vol. 9, no. 1
p. e85363

Abstract

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BACKGROUND: Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent. METHODOLOGY: We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D') for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. PRINCIPAL FINDINGS: We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310'C' insertion (P = 0.018), T16189C (P = 0.0019) variants and 310'C'ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D' = 0.49) as compared to patients (D' = 0.14). CONCLUSIONS: Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer.