Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest

Abstract

Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection.

The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved

“…30 Conversely, in these populations, the haplogroups I, H and the superhaplogroup UK were associated to an increased risk for breast, colon and vulvar cancers, respectively. 16,31 Whereas most of mtDNA polymorphism increased the cancer risk, others declined the risk in certain types of cancer. In West Eurasian populations, the risk for endometrial cancer is reduced with haplogroup H, which has the highest frequency in these populations.…”

“…Other HPVs, with a frequency o1%, were found in the tumor sample, including HPV types 73, 53, 39, 6, 61, 68, 11 and 69, which account for the remaining 4.3% of HPV-positive samples (Supplementary Table 1). In the control women, HPV16 was also the most common viral type (4.8%), followed by HPV types31, 58, 53,18, 56, 66,6, 61, 71,45, 68,29,32, 70, 90 and 97, all of them with a frequency o1.5%.The risk for CC associated to HPV infection was calculated by unconditional logistic regression and is shown inTable 1. The OR of all HPVs together was 152.9 (95% confidence interval (CI): 65.4-357.5).…”

Mitochondrial DNA Haplogroup R Confers a Genetic Risk Factor for Intrauterine Adhesion in Han Women Population

“…The mtDNA G10398A polymorphism of haplogroup N resulted in an amino acid change, alanine → threonine, within the nicotinamide adenine dinucleotide dehydrogenase (ND) 3 subunit of complex I of mtDNA electron transport chain, has been shown to cause an increased rate of electron leakage and is related to the development of breast and esophageal cancer [22]. The mitochondrial haplogroups, haplotype ‘10398A/​10400C/13603AG' and haplogroup N that are correlated with mitochondrial function, are higher risk factors for endometrial associated diseases including endometrial cancer [23] and endometriosis [24]. These findings suggest that the exact locus polymorphisms of mtDNA may affect the prognosis of the diseases associated with mitochondrial function.…”

Mitochondrial haplogroups and control region polymorphisms in Kaposi's sarcoma patients

“…Various mitochondrial haplogroups have been shown to produce different amounts of superoxide and other ROS molecules [Marcuello et al, ], resulting in different amounts of oxidative stress in cells based on their haplogroup [Cai et al, ; Herrnstadt & Howell, 2004]. mtDNA haplogroups have also been related to several multifactorial diseases including neurodegenerative diseases [Gaweda‐Walerych et al, ; Santoro et al, ], depressive disorders [Rollins et al, ], cancer [Bai et al, ; Ebner et al, ; Klemba et al, ] and microbial infections [Hendrickson et al, ; Klemba et al, ].…”