Association between mitochondrial DNA haplogroup and myelodysplastic syndromes

Abstract

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System (MCSS). Controls were identified through the Minnesota State driver’s license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non-Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS-R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H+V), JT (J+T), IWX (I+W+X), UK (U+K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR=0.58, 95% CI 0.36, 0.92, P=0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population-based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes.

Overview of mitochondrial germline variants and mutations in human disease: Focus on breast cancer (Review)

“…Haplogroups reflect specific ancestral populations and are the result of sequential accumulation of mitochondrial mutations through maternal lineages; hence, they present continent-specific distributions. The molecular mechanisms underlying the association between mtDNA haplogroups and cancer development remains unclear and controversial results between populations have been reported (65)(66)(67)(68)(69)(70)(71)(72)(73). However, specific mtDNA haplogroups have been associated with the risk of prostate cancer, BC, CC, nasopharyngeal cancer, gastric cancer, myelodysplastic syndromes (MS), acute lymphoblastic leukemia, etc.…”

“…However, specific mtDNA haplogroups have been associated with the risk of prostate cancer, BC, CC, nasopharyngeal cancer, gastric cancer, myelodysplastic syndromes (MS), acute lymphoblastic leukemia, etc. (65)(66)(67)(68)(69)(70)(71)(72)74). For example, an over-representation of haplogroup I in Polish cancer patients has been reported (75), haplogroup U has been shown to be associated with an increased risk of developing renal and prostate cancers (65), and haplogroup JT has been shown to be associated with MS susceptibility in North American caucasion subjects (70).…”

“…(65)(66)(67)(68)(69)(70)(71)(72)74). For example, an over-representation of haplogroup I in Polish cancer patients has been reported (75), haplogroup U has been shown to be associated with an increased risk of developing renal and prostate cancers (65), and haplogroup JT has been shown to be associated with MS susceptibility in North American caucasion subjects (70). Additionally, haplogroups H, N and L have been shown to be associated with the risk of developing pancreatic cancer, whereas haplogroup K has been identified as protective for this type of cancer in participants from the San Francisco Bay Area in California (76).…”

Mitochondrial DNA (mtDNA) and Cancer Pathogenesis – The Role of mtDNA Mutations: A Review

“…The molecular mechanisms that are responsible for the association between mtDNA haplogroups and cancer development remains unclear and previous reports have shown controversial results (Booker et al, 2006;Fang et al, 2010;Hu et al, 2014;Li et al, 2015;Poynter et al, 2016;Singh and Kulawiec, 2009;Cano et al, 2014). Nevertheless, specific mtDNA haplogroups have been associated with the risk of prostate, colorectal, nasopharyngeal, gastric cancer, myelodysplastic syndromes, acute lymphoblastic leukemia, etc.…”

“…Nevertheless, specific mtDNA haplogroups have been associated with the risk of prostate, colorectal, nasopharyngeal, gastric cancer, myelodysplastic syndromes, acute lymphoblastic leukemia, etc. (Yu et al, 2016;Booker et al, 2006;Fang et al, 2010;Hu et al, 2014;Poynter et al, 2016;Singh and Kulawiec, 2009).…”