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


METHODS
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.


RESULTS
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.
Department of Genetics, Osmania University, Hyderabad, India.
Nageswara Rao
NR
Tipirisetti
Department of Biochemistry, Osmania University, Hyderabad, India.
Suresh
S
Govatati
Department of Biotechnology, Periyar University, Salem, Tamilnadu, India.
Priyanka
P
Pullari
Department of Biochemistry, DrMRAR PG Center, Krishna University, Nuzvid, India.
Sravanthi
S
Malempati
Department of Biotechnology, Chaitanya Postgraduate College, Hanamkonda, India.
Murali Krishna
MK
Thupurani
Department of Biochemistry, Osmania University, Hyderabad, India.
Shyam
S
Perugu
Department of Biochemistry, Osmania University, Hyderabad, India.
Praveen
P
Guruvaiah
Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.
Lakshmi
L
Rao K
Nizam's Institute of Medical Sciences, Hyderabad, India.
Raghunadha Rao
RR
Digumarti
Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, India.
Varadacharyulu
V
Nallanchakravarthula
Department of Biochemistry, Osmania University, Hyderabad, India.
Manjula
M
Bhanoori
Department of Genetics, Osmania University, Hyderabad, India.
Vishnupriya
V
Satti
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid; D012307:Risk Factors
D004272:DNA, Mitochondrial