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Mitochondrial DNA 4977‐base pair common deletion in blood leukocytes and melanoma risk
Author(s) -
Shen Jie,
Wan Jie,
Huff Chad,
Fang Shenying,
Lee Jeffrey E.,
Zhao Hua
Publication year - 2016
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12474
Subject(s) - mitochondrial dna , sunburn , melanoma , dna damage , odds ratio , oxidative stress , carcinogenesis , medicine , dna , biology , microbiology and biotechnology , immunology , genetics , cancer , cancer research , dermatology , gene
Summary The 4977‐base pair common deletion Dmt DNA 4977 is the most frequently observed mitochondrial DNA mutation in human tissues. Because mitochondrial DNA mutations are mainly caused by reactive oxygen species ( ROS ), and given that oxidative stress plays an important role in melanoma carcinogenesis, the investigation of Dmt DNA 4977 may be particularly relevant to the development of melanoma. In this study, we compared Dmt DNA 4977 levels in blood leukocytes from 206 melanoma patients and 219 healthy controls. Overall, melanoma cases had significantly higher levels of Dmt DNA 4977 than healthy controls (median: 0.60 vs 0.20, P = 0.008). The difference was evident among individuals who were older than 47 yrs, women, and had pigmentation risk factors (e.g., blond or red hair, blue eye, fair skin, light, or none tanning ability after prolonged sun exposure, and freckling in the sun as a child). The difference was also evident among those who had at least one lifetime sunburn with blistering and had no reported use of a sunlamp. Interestingly, among controls, Dmt DNA 4977 levels differed by phenotypic index and reported use of a sunlamp. In the risk assessment, increased levels of Dmt DNA 4977 were associated with a 1.23‐fold increased risk of melanoma (odds ratio ( OR ): 1.23, 95% confidence interval (90% CI ): 1.01, 1.50). A significant dose–response relationship was observed in quartile analysis (P = 0.001). In summary, our study suggests that high levels of Dmt DNA 4977 in blood leukocytes are associated with increased risk of melanoma and that association is affected by both pigmentation and personal history of sun exposure.