Blood leukocyte DNA hypomethylation and gastric cancer risk in a high-risk Polish population

Lifang Hou, Hao Wang, Samantha Sartori, Andrew Gawron, Jolanta Lissowska, Valentina Bollati, Letizia Tarantini, Fang Fang Zhang, Witold Zatonski, Wong Ho Chow, Andrea Baccarelli

Research output: Contribution to journalArticle

Abstract

Global hypomethylation has been shown to increase genome instability potentially leading to increased cancer risk. We determined whether global methylation in blood leukocyte DNA was associated with gastric cancer in a population-based study on 302 gastric cancer cases and 421 age-and sex-matched controls in Warsaw, Poland, between 1994 and 1996. Using PCR-pyrosequencing, we analyzed methylation levels of Alu and LINE-1, 2 CG-rich repetitive elements, to measure global methylation levels. Gastric cancer risk was highest among those with lowest level of methylation in either Alu (OR = 1.3, 95% CI = 0.91.9) or LINE-1 (OR = 1.4, 95% CI = 0.92.0) relative to those with the highest levels, although the trends were not statistically significant. For Alu, the association was stronger among those aged 70 or older (OR = 2.6, 95% CI = 1.35.5, p for interaction = 0.02). We did not observe meaningful differences in the associations by other risk factors and polymorphisms examined. For LINE-1, the association tended to be stronger among individuals with a family history of cancer (OR = 3.1, 95% CI = 1.47.0, p for interaction = 0.01), current alcohol drinkers (OR = 1.9, 95% CI = 1.03.6, p for interaction = 0.05), current smokers (OR = 2.3, 95% CI = 1.14.6, p for interaction = 0.02), those who rarely or never consumed fruit (OR = 3.1, 95% CI = 1.28.1, p for interaction = 0.03), CC carriers for the MTRR Ex5+123C>T polymorphism (OR = 2.3, 95% CI = 1.24.4, p for interaction = 0.01) and TT carriers for the MTRR Ex15+572T>C polymorphism (OR = 1.7, 95% CI = 1.02.8, p for interaction = 0.06). The association was not different by sex, Helicobacter pylori infection, intake of folate, vitamin B6 and total protein and the remaining polymorphisms examined. Our results indicate that interactions between blood leukocyte DNA hypomethylation and host characteristics may determine gastric cancer risk.

Original languageEnglish
Pages (from-to)1866-1874
Number of pages9
JournalInternational Journal of Cancer
Volume127
Issue number8
DOIs
Publication statusPublished - Oct 15 2010

Keywords

  • gastric cancer
  • gastric cancer risk
  • global hypomethylation
  • methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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    Hou, L., Wang, H., Sartori, S., Gawron, A., Lissowska, J., Bollati, V., Tarantini, L., Zhang, F. F., Zatonski, W., Chow, W. H., & Baccarelli, A. (2010). Blood leukocyte DNA hypomethylation and gastric cancer risk in a high-risk Polish population. International Journal of Cancer, 127(8), 1866-1874. https://doi.org/10.1002/ijc.25190