Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case–Control Study

Mendoza-Pérez, Julia; Gu, Jian; Herrera, Luis A.; Tannir, Nizar M.; Matin, Surena F.; Karam, Jose A.; Huang, Maosheng; Chang, David W.; Wood, Christopher G.; Wu, Xifeng

doi:10.1158/1078-0432.ccr-15-0977

Cited by 22 publications

(19 citation statements)

References 44 publications

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“…Our results are consistent with previous studies in patients with bladder cancer, 5 colorectal adenoma, 8,9 breast cancer, 11 melanoma 14 or kidney cancer, 25 where the authors reported that global hypomethylation of leukocyte DNA, measured as 5-mC% level, was associated with increased risk of cancer. Our results are also in line with several other studies in head and neck cancer, 2 bladder cancer, 6,7 testicular cancer, 26 breast cancer, 27 gastric cancer 3 and hepatocellular carcinoma 4 in which the authors reported that lower methylation levels of repetitive elements were associated with increased risk of cancer.…”

Section: Discussionsupporting

confidence: 93%

Global methylation of blood leukocyte DNA and risk of melanoma

Shen

Song

Wan

et al. 2017

Intl Journal of Cancer

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Global DNA methylation, possibly influenced by lifestyle and environmental factors, has been suggested to play an active role in carcinogenesis. However, its role in melanoma has rarely been explored. The aims of this study were to evaluate the relationship between melanoma risk and expression of 5-methylcytosine (5-mC), a marker for global DNA methylation, in blood leukocyte DNA, and to determine whether this 5-mC level is influenced by pigmentation and sun exposure. This case-control study included 540 melanoma cases and 540 healthy controls. Overall, melanoma cases had significantly lower levels of 5-mC% than healthy controls (median: 3.24 vs 3.91, P<0.001). The significant difference between two groups did not differ by pigmentation or sun exposure. Among healthy controls, however, those who had fair skin color (P=0.041) or light or no tanning after prolonged sun exposure (P=0.031) or used a sunlamp (P=0.028) had lower levels of 5-mC% than their counterparts. In addition, those with an intermediate or high phenotypic index, an indicator of cutaneous cancer susceptibility, had 2.58-fold greater likelihood of having a low level of 5-mC% (odds ratio [OR]: 2.58; 95% confidence interval [CI]: 1.72, 3.96) than those with a low phenotypic index. Lower levels of 5-mC% were associated with a 1.25-fold greater risk of melanoma (OR: 1.25; 95% CI: 1.08, 1.37). A significant dose-response relationship was observed in quartile analysis (P=0.001). Our results suggest that global hypomethylation in blood leukocyte DNA is associated with increased risk of melanoma and that the level of methylation is influenced by pigmentation and sun exposure.

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Section: Discussionsupporting

confidence: 93%

Global methylation of blood leukocyte DNA and risk of melanoma

Shen

Song

Wan

et al. 2017

Intl Journal of Cancer

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“…This suggests that the role of global DNA hypomethylation in cancer development is more than a mediator or effector of carcinogen exposure. Similar differences have been reported previously [ 19 ]. For example, Mendoza-Perez et al found that the significant association between global DNA hypomethylation and renal cell carcinoma was limited to younger individuals [ 19 ].…”

Section: Discussionsupporting

confidence: 93%

“…Our results confirm the positive association between global DNA hypomethylation in leukocytes and cancer risk reported in several other cancer sites, including head and neck [ 3 ], testes [ 18 ], stomach [ 4 ], hepatocellular carcinoma [ 5 ], bladder [ 6 – 8 ], colon and rectum [ 9 , 10 ], breast [ 12 ], melanoma [ 15 , 16 ], and kidney [ 19 ]. The consistency among those studies demonstrates that DNA hypomethylation is a key and frequent genetic event contributing to cancer development.…”

Section: Discussionsupporting

confidence: 87%

Global DNA hypomethylation in leukocytes associated with glioma risk

et al. 2017

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Global DNA hypomethylation in leukocytes has been associated with increased risk for a variety of cancers. However, the role of leukocyte global DNA hypomethylation in glioma development, if any, is largely unknown. To define this role, we performed a case-control study with 390 glioma patients and 390 controls with no known cancer. Levels of 5-methylcytosine (5-mC%), a marker for global DNA methylation, were measured in leukocyte DNA. Overall, median levels of 5-mC% were significantly lower in glioma cases than in controls (3.45 vs 3.82, P=0.001). Levels of 5-mC% differed significantly by age and sex among controls and by tumor subtype and grade among glioma cases. In multivariate analysis, lower levels of 5-mC% were associated with a 1.31-fold increased risk of glioma (odds ratio = 1.31, 95% confidence interval = 1.10-1.41). A significant dose-response trend was observed in quartile analysis (P=0.001). In an analysis further stratified by clinical characteristics at baseline, the association between lower levels of 5-mC% and glioma risk was evident only among younger participants (age <52 years), women, and those with aggressive tumor characteristics, such as glioblastoma subtype, high tumor grade (grade III or IV), and absence of IDH1 mutation. Our findings indicate that global DNA hypomethylation in leukocytes may contribute to the development of glioma and that the association is affected by age, sex, and tumor aggressiveness.

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“…DNA hypomethylation can potentially activate oncogenes and cause genetic instability if affecting repetitive genomic DNA elements that may lead to the initiation of carcinogenesis ( Besaratinia et al , 2013 ). Global hypomethylation of DNA from peripheral blood collected years before diagnosis has been associated with the risk of several common cancers when measured with bisulphite sequencing assessment of % 5-mC content or surrogate measures of global DNA methylation ( Woo and Kim, 2012 ; Brennan and Flanagan, 2012b ; Mendoza-Perez et al , 2015 ). Recently, genome-wide measures of DNA methylation derived from the Illumina HumanMethylation450 assay (Illumina Inc., San Diego, CA, USA) have been prospectively associated with the risk of several cancers, including breast cancer ( Severi et al , 2014 ; van Veldhoven et al , 2015 ) and B-cell lymphoma ( Wong Doo et al , 2016 ).…”

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confidence: 99%

Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case–control study

et al. 2016

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Background:Global DNA methylation has been reported to be associated with urothelial cell carcinoma (UCC) by studies using blood samples collected at diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide measures of blood DNA methylation and assessed them for their prospective association with UCC risk.Methods:We used 439 case–control pairs from the Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA sample type, and collection period. Conditional logistic regression was used to compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA methylation and 95% confidence intervals (CIs), adjusted for potential confounders. We also investigated associations by disease subtype, sex, smoking, and time since blood collection.Results:The risk of superficial UCC was decreased for individuals with higher levels of our genome-wide DNA methylation measure (OR=0.71, 95% CI: 0.54–0.94; P=0.02). This association was particularly strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27–0.83). Intermediate levels of our genome-wide measure were associated with decreased risk of invasive UCC. Some variation was observed between UCC subtypes and the location and regulatory function of the CpGs included in the genome-wide measures of methylation.Conclusions:Higher levels of our genome-wide DNA methylation measure were associated with decreased risk of superficial UCC and intermediate levels were associated with reduced risk of invasive disease. These findings require replication by other prospective studies.

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Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case–Control Study

Cited by 22 publications

References 44 publications

Global methylation of blood leukocyte DNA and risk of melanoma

Global methylation of blood leukocyte DNA and risk of melanoma

Global DNA hypomethylation in leukocytes associated with glioma risk

Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case–control study

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