TY - JOUR
T1 - Blood leukocyte DNA hypomethylation and gastric cancer risk in a high-risk Polish population
AU - Hou, Lifang
AU - Wang, Hao
AU - Sartori, Samantha
AU - Gawron, Andrew
AU - Lissowska, Jolanta
AU - Bollati, Valentina
AU - Tarantini, Letizia
AU - Zhang, Fang Fang
AU - Zatonski, Witold
AU - Chow, Wong Ho
AU - Baccarelli, Andrea
PY - 2010/10/15
Y1 - 2010/10/15
N2 - 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.
AB - 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.
KW - gastric cancer
KW - gastric cancer risk
KW - global hypomethylation
KW - methylation
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U2 - 10.1002/ijc.25190
DO - 10.1002/ijc.25190
M3 - Article
C2 - 20099281
AN - SCOPUS:77956993739
SN - 0020-7136
VL - 127
SP - 1866
EP - 1874
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 8
ER -