Elevated mRNA levels of DNA methyltransferase‐1 as an independent prognostic factor in primary nonsmall cell lung cancer

Abstract

Objective We documented previously that if study quality is accounted for, evidence from occupational cohort studies on benzene supports a possible association with some lymphoma subtypes, in particular multiple myeloma, and acute and chronic lymphocytic leukemia. Here, we extend these analyses to chronic myeloid leukemia (CML). Methods Three strategies to assess study quality (stratification by the year‐of‐start of follow‐up, stratification by the strength of the reported acute myeloid leukemia (AML) association, and stratification by the quality of benzene exposure assessment) were employed in a meta‐analysis of occupational benzene exposure and CML. We hypothesized that stratification by these study quality dimensions would identify a subgroup of occupational cohort studies that is most informative for the evaluation of the possible association between benzene and CML. Results The overall meta‐relative risk (mRR) was non‐significantly elevated (1.23; 95% confidence interval (CI): 0.93–1.63). The mRRs increased with increasing study quality for all dimensions with a significant elevation for studies with start of follow‐up after 1970 (1.67; 95% CI: 1.02–2.74). The highest study quality stratum for AML significance and exposure quality showed an elevated but non‐significant increased mRR (1.40; 95% CI: 0.86–2.27, and 1.68; 95% CI: 0.74–3.84, respectively). Conclusions Although limited by low statistical power, the current meta‐analysis provides support for a possible association of occupational exposure to benzene and the risk of CML. Am. J. Ind. Med. 55:779–785, 2012. © 2012 Wiley Periodicals, Inc.

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

“…The importance of both DNMT1 and DNMT3B expression in the maintenance of aberrant CpG island methylation of TSGs in mammalian cell models 20,[53][54][55] has been demonstrated. Our data together with previous reports [20][21][22] suggest that DNMT1 and DNMT3B can regulate DNA methylation in a promoter-specific manner. In concordance with this suggestion is the classification of common and distinct promoter groups identified after RNA interference-mediated suppression of DNMT1 and DNMT3B.…”

“…All these genes were overexpressed in NSCLC tissues, in concordance with previous reports in other human cancer types. [17][18][19]21,47,48 A strong correlation between the expression levels of all the DNMTs was observed, in accordance with a reported coordinated expression of DNMTs. 22,47 Furthermore, the expression levels of all DNMTs examined in this set was correlated with the expression of E2F1.…”

“…21,22 In addition, DNMT3B overexpression was correlated with hypermethylation of RASSF1 but not CDKN2A promoter. Interestingly, the same finding was reported for DDNMT3B in NSCLC.…”

“…15,16 Numerous studies have demonstrated frequent overexpression of the DNMTs in many cancer types, [17][18][19] which in some cases correlated with the hypermethylation of particular TSGs. [20][21][22] However, other reports suggest that DNMT overexpression does not by itself seem to sufficiently account for the hypermethylation of TSG promoters. 19,21,23,24 UHRF1 (also known as ICBP90) has recently been shown to play an important role in methylation maintenance.…”

“…[20][21][22] However, other reports suggest that DNMT overexpression does not by itself seem to sufficiently account for the hypermethylation of TSG promoters. 19,21,23,24 UHRF1 (also known as ICBP90) has recently been shown to play an important role in methylation maintenance. 25 It has the ability to bind hemimethylated DNA through its SET-and RING-associated domain, 26,27 triggering the recruitment of DNMT1 25,28 and histone deacetylace-1.…”