Table 1. Studies on global DNA hypomethylation in peripheral blood leukocytes and cancer risk included in the meta-analysis.
| Author (Year) | Methods | Cancer site | Country | Study period | No. cases/controls | Category | OR (95% CI) | P trend | Confounding variables that were considered |
| Case-control studies | |||||||||
| Pufulete | Methyl | Colorectal | UK | 2000 | 76/ | T1 (Adenoma) | 1 | 0.01 | Age, sex, body mass index, |
| (2003)(36) | acceptance | −2001 | (35 adenoma | T2 | 6.68 (0.99–45.12) | smoking status, and alcohol | |||
| assay | and 28 cancer) | T3 | 10.27 (2.05–51.46) | intake | |||||
| T1 (Cancer) | 1 | 0.08 | |||||||
| T2 | 2.98 (0.51–17.40) | ||||||||
| T3 | 4.90 (0.84–28.53) | ||||||||
| Hsiung | LINE-1 | HNSCC | USA | 1999 | 278/526 | T3 (>76.9) | 1 | 0.03 | Age, sex, race, smoking |
| (2007) (37) | (LRE1) | −2003 | T2 (73.6-0.76.9) | 1.3 (0.9–2.0) | history, lifetime average | ||||
| T1 (<73.6) | 1.6 (1.1–2.4) | alcoholic drinks weekly, | |||||||
| and positive HPV16 serology | |||||||||
| LIM | %5-mC | Colorectal | USA | 2000 | 115/115 | T3 (5.43–6.42) | 1† | 0.002 | Matching factors (age and |
| (2008) (38) | Adenoma | −2002 | T2 (5.29–5.43) | 0.39 (0.66–2.94) | month of blood draw), | ||||
| T1 (2.76–5.29) | 5.88 (2.04–16.67) | smoking history, and red | |||||||
| meat intake | |||||||||
| Moore | %5-mC | Bladder | Spain | 1998 | 775/397 | Q4 (≥3.68) | 1 | <0.001 | Age, sex, region, smoking |
| (2008) (39) | −2001 | Q3 (3.19–3.68) | 2.05 (1.37–3.06) | status, pack-years, interaction | |||||
| Q2 (2.46–3.19) | 1.62 (1.07–2.44) | (smoking status, pack-year) | |||||||
| Q1 (<2.46) | 2.67 (1.77–4.03) | ||||||||
| Choi | %5-mC | Breast | USA | 179/180 | T3 | 1 | <0.001 | Age, race, and batches | |
| (2009) (40) | T2 | 1.49 (0.84–2.65) | |||||||
| T1 | 2.86 (1.65–4.94) | ||||||||
| Hou | LINE-1, | Gastric | Poland | 1994 | 302/421 | T3 (81.7–90.4) | 1 | 0.12 | Age, sex, educational level, |
| (2010) (41) | Alu | −1996 | T2 (78.6–81.7) | 1.2 (0.8–1.8) | smoking, and alcohol | ||||
| T1 (67.6–78.6) | 1.4 (0.9–2.0) | ||||||||
| Wilhelm | LINE-1 | Bladder | USA | 1994 | 285/465 | 74.25–91.96 (90%) | 1 | Age and sex | |
| (2010) (42) | −1998 | 57.89-74.25 (10%) | 1.8 (1.12–2.90) | ||||||
| Cash | LINE-1 | Bladder | China | 1995 | 510/528 | T3 (≥82.52) | 1 | 0.268 | Age at reference date, sex, |
| (2011) (43) | −1998 | T2 (81.22–82.52) | 1.10 (0.81–1.50) | and family history of cancer | |||||
| T1 (<81.22) | 1.28 (0.95–1.73) | ||||||||
| Liao(44) | LINE-1 | Renal cell | Central | 1999 | 328/654 | Q4 (86.0–90.2) | 1† | 0.004 | Age, sex, center, smoking status |
| (2011) | and | −2003 | Q3 (81.7–83.0) | 0.58 (0.38–0.90) | BMI, high blood pressure, and | ||||
| Eastern | Q2 (80.3–81.7) | 0.54 (0.36–0.83) | vegetable intake | ||||||
| Europe | Q1 (78.4–83.6) | 0.49 (0.32–0.75) | |||||||
| Nested case-control study | |||||||||
| Gao(45) | LINE-1, | Stomach | China | 1997 | 192/384 | Q4 | 1 | Age | |
| (2011) | Alu | −2009 | Q3 | 0.73 (0.44–1.21) | |||||
| Q2 | 1.02 (0.64–1.60) | ||||||||
| Q1 | 0.89 (0.54–1.46) | ||||||||
| Cohort studies | Incidence/total | ||||||||
| Zhu | LINE-1, | All | USA | 1963 | 29/517 | High (86.2-77.2) | 1 | Age, BMI, race, education, | |
| (2011) (46) | Alu | −1999 | Low (77.1-68.1) | 3.0 (1.3–6.9) | smoking status, pack-years, | ||||
| and alcohol drinking | |||||||||
†
OR (95% CI) was recalculated because the reference was the lowest tertile of genomic methylation in the original result.
T: tertile, Q: quartile, %5-mC: percentage of 5-methyl cytosine, LINE-1: long interspersed nucleotide element 1, LRE1: LINE retrotransposable element 1.