Potential Association of Mitochondrial Haplogroups and A8860G Mutation with Breast Cancer Risk

Abstract

The last decade has witnessed great progresses regarding the molecular basis of breast cancer with discovery of different nuclear susceptibility genes; in addition investigations and researches regarding mitochondrial DNA (mtDNA) mutations in breast cancer have been started. Mitochondrial haplogroup determinants (single nucleotide polymorphism SNP) and somatic mitochondrial mutations have recently been studied as possible risk factors for carcinogenic processes in different tissues, hence in order to identify breast cancer related SNPs and haplogroups among the population of Sulaimaniyah city/Iraq, the entire mitochondrial genome of 20-breast cancer samples and comparable controls were sequenced. Haplogrep 2.0 was used for haplogroup identification; Chi-square and Fishers exact test were applied to assess relational significance. HV haplogroup in the cancer samples appeared to be a risk factor for breast cancer compared to the most common H haplogroup in control samples with a p-values of 0.002 and 0.006 respectively and an Odd Ratio (OR) = 28.00. Besides, SNP (A8860G) was also identified as a risk factor for breast cancer as compared to other randomly selected SNPs (A750G, A1438G and C7028T) with p values <0.05 and OR >1.

Breast Cancer and Mitochondrial Dna Mutations in Kurdish Women: A Case-Control Study From Sulaymaniyah, Iraq.

“…B reast cancer is a heterogeneous, debilitating disease of a multistep carcinogenic background [1][2][3] . It is the most frequently diagnosed cancer in women [2][3][4] .…”

“…B reast cancer is a heterogeneous, debilitating disease of a multistep carcinogenic background [1][2][3] . It is the most frequently diagnosed cancer in women [2][3][4] . The incidence of breast cancer among women in Kurdistan region, Iraq approaches the western countries and could be even higher particularly in the young 2,3,5 .…”

“…It is the most frequently diagnosed cancer in women [2][3][4] . The incidence of breast cancer among women in Kurdistan region, Iraq approaches the western countries and could be even higher particularly in the young 2,3,5 . "Although, major progresses have been made over the past decade in exploring the molecular basis of breast cancer and the discovery of several susceptibility nuclear-genes of high, moderate and low penetrance as predisposing factors for breast cancer, these genes hardly explain 10-15% of the cases" 2,3,6 .…”

“…They retain a small DNA genome. Mitochondrial DNA (mtDNA) is a circular molecule of 16,569 bp, coding for 2 ribosomal RNAs (12S and 16S), 22 transfer RNAs and 13 essential protein subunits of the oxidative phosphorylation system (OXPHOS)" 2,3 . "The only non-coding region is the D-loop region (displacement-region), which has been identified as a regulatory region of mtDNA replication and transcription, containing a replication origin and promoter region" 7 .…”

“…Otto Warburg, in 1956, observed that cancers ferment glucose in the presence of oxygen. Accordingly, Warburg proposed that abnormalities in mitochondrial respiration may be responsible for cancer production" 2,3,8 .…”