Authors Methylation Type Measurement method Study participants Findings Comments Physical activity Duggan et al., 2014 [24 ] LINE-1 Pyrosequencing 300 overweight women aged 50–75 in the US No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences White et al., 2013 [49 ] LINE-1 Pyrosequencing 647 non-Hispanic white women aged 35–74 from the NIH sister study, USA Significant differences ( Physical activity levels of women greater than or equal to the median of physical activity at three time points (ages 5–12, 13–19 and currently) had higher global methylation compared to women with activity levels below the median for all three time periods (beta = .33, 95% CI: .01, 0.66) Zhang et al., 2011 [50 ] LINE-1 MethyLight 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Alcohol Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Hsiung et al., 2007 [28 ] LINE-1 COBRA PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area No differences Adjusted for age, sex, race, smoking, HPV serology, dietary folate, MTHFR Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO - 436 controls from individuals aged 55–74 in the US, ATBC, 575 controls from individuals aged 55–69 in Finland PLCO -No differences Mirabello et al., 2010 [32 ] LINE-1 Pyrosequencing 314 individuals aged 12–75+ from the NCI Clinical Genetics Branch Familial TGTC Study in the US No differences Pearce et al., 2012 [33 ] LINE-1 Pyrosequencing 228 individuals aged 49–51 from Newcastle, England No differences Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Zhu et al., 2012 [38 ] LINE-1 Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Zhu et al., 2012 [38 ] Au Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Kim et al., 2010 [40 ] Alu Pyrosequencing 86 individuals aged 42–69, South Korea No differences Adjusted for age Na et al., 2014 [41 ] Alu Pyrosequencing 244 women aged 20–51, Korea No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Smoking Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Andreotti et al., 2014 [45 ] LINE-1 Pyrosequencing 676 individuals aged 55–74 from the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) in the US No difference for females. Significant differences ( “Never” smoked had 84% average LINE-1 methylation% and “Ever” smoked had 83.6% average LINE-1 methylation% for males Gomes et al., 2012 [26 ] LINE-1 ELISA 126 individuals aged 60–88, Brazil No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Hsiung et al., 2007 [28 ] LINE-1 COBRA PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area No differences Adjusted for age, sex, race, alcohol, HPV serology, dietary folate, MTHFR Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO - 436 controls from individuals aged 55–74 in the US PLCO - No differences for females. Significant difference ( PLCO, males who had never smoked have an average 77.35% LINE-1 methylation%, and males who had ever smoked have an average 77.02% LINE-1 methylation% Liao et al., 2011 [30 ] LINE-1 Pyrosequencing 654 individuals aged 20–79 from the Central and Eastern European Renal Cancer Study (CEERCC) No differences Mirabello et al., 2010 [32 ] LINE-1 Pyrosequencing 314 individuals aged 12–75+ from the NCI Clinical Genetics Branch Familial TGTC Study in the US No differences Pearce et al., 2012 [33 ] LINE-1 Pyrosequencing 228 individuals aged 49–51 from Newcastle, England No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Adjusted for age, sex, region Wilhelm et al., 2010 [35 ] LINE-1 Pyrosequencing 465 individuals aged 25–74, from NH No differences Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhu et al., 2012 [38 ] LINE-1 Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Kim et al., 2010 [40 ] Alu Pyrosequencing 86 individuals aged 42–69, South Korea No differences Adjusted for age Na et al., 2014 [41 ] Alu Pyrosequencing 244 women aged 20–51, Korea No differences Rusiecki et al., 2008 [42 ] Alu Pyrosequencing 70 individuals aged 19–67 from Greenlandic Inuit, Greenland No differences Zhu et al., 2012 [38 ] Alu Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Moore et al., 2008 [44 ] 5-mdC HPCE, HpaII digest, densitometry 397 individuals aged 20–81 from the Spanish Bladder Cancer Study, Spain No differences BMI Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Duggan et al., 2014 [24 ] LINE-1 Pyrosequencing 300 overweight women aged 50–75 in the US No differences Gomes et al., 2012 [26 ] LINE-1 ELISA 126 individuals aged 60–88, Brazil No differences Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO, 436 controls from individuals aged 55–74 in the US, ATBC, 575 controls from individuals aged 55–69 in Finland PLCO, no differences. ATBC, significant differences between 16.7–<25, 25–30, and 30–62.1 BMI 16.7–<25 had 79.00% average LINE-1 methylation%, BMI 25–30 had 78.73% average LINE-1 methylation%, and BMI 30–62.1 had 78.39% average LINE-1 methylation% Liao et al., 2011 [30 ] LINE-1 Pyrosequencing 654 individuals aged 20–79 from the Central and Eastern European Renal Cancer Study (CEERCC) No differences Marques-Rocha, 2016 [31 ] LINE-1 MS-HRM 156 individuals aged 19–27, Brazil No differences Pearce et al., 2012 [33 ] LINE-1 Pyrosequencing 228 individuals aged 49–51 from Newcastle, England No differences Adjusted for sex Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences In unadjusted models, there was a statistically significant difference ( Zhu et al., 2012 [38 ] LINE-1 Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Kim et al., 2010 [40 ] Alu Pyrosequencing 86 individuals aged 42–69, South Korea No differences Adjusted for age Na et al., 2014 [41 ] Alu Pyrosequencing 244 women aged 20–51, Korea Significant difference ( Normal weight had 26.28 Alu methylation%, overweight had 24.95 Alu methylation%, normal weight had 25.96 Alu methylation% Zhu et al., 2012 [38 ] Alu Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Vegetables Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Cash et al., 2012 [46 ] LINE-1 Pyrosequencing 528 individuals aged 25–74 from the Residents Registry of the Shanghai Municipal Government, China Significant differences ( Men with “<4 times/week” intake of total cruciferous vegetables had 81.31 average LINE-1 methylation% and men with “≥4 times/week” intake of total cruciferous vegetables had 82.2 average LINE-1 methylation% Duggan et al., 2014 [24 ] LINE-1 Pyrosequencing 300 overweight women aged 50–75 in the US No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO - 436 controls from individuals aged 55–74 in the US, ATBC, 575 controls from individuals aged 55–69 in Finland PLCO, No differences. ATBC, significant differences ( <690.9 grams of vegetables per day have an average 78.64% LINE-1 methylation%, and ≥690.6 grams of vegetables per day have an average 78.90% LINE-1 methylation% Liao et al., 2011 [30 ] LINE-1 Pyrosequencing 654 individuals aged 20–79 from the Central and Eastern European Renal Cancer Study (CEERCC) No differences Martín-Núñez et al., 2014 [51 ] LINE-1 Pyrosequencing 155 individuals aged 40–65 from Spain LINE-1 methylation increased in the control group ( The control group had 66.8 average LINE-1 methylation% and the intervention group had 63.6 average LINE-1 methylation% after one year. Adjusted for age, gender, BMI at baseline Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Adjusted for age, sex, region, smoking status Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Fruit Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki Significant differences ( Data given in tertiles of methylation; women with <201 grams/day fruit intake had lower average LINE-1 methylation% than women with >201 grams/day fruit intake Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO, 436 controls from individuals aged 55–74 in the US, ATBC, 575 controls from individuals aged 55–69 in Finland PLCO, No differences. ATBC, No differences Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Adjusted for age, sex, region, smoking status Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Folate Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki Significant differences ( Data given in tertiles of methylation; women with folate deficiency had lower average LINE-1 methylation% than women without folate deficiency Bae et al., 2014 [52 ] LINE-1 LC-MS/MS 408 women aged 50–79 from the WHI-OS cohort, throughout the US Significant differences ( Women in “highest RBC folate group” had 5.12 baseline LINE-1 methylation% and women in “lowest RBC folate group” had 4.99 baseline LINE-1 methylation% Gomes et al., 2012 [26 ] LINE-1 ELISA 126 individuals aged 60–88, Brazil No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Hsiung et al., 2007 [28 ] LINE-1 COBRA PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area No differences Adjusted for age, sex, race, smoking, alcohol, HPV serology, MTHFR Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO, 436 controls from individuals aged 55–74 in the US, ATBC, 575 controls from individuals aged 55–69 in Finland PLCO, No differences. ATBC, No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Adjusted for age, sex, region Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY Significant differences ( Dietary folate from fortified foods, µ g/1,000 kJ spearman value 0.21 Moore et al., 2008 [44 ] 5-mdC HPCE, HpaII digest, densitometry 397 individuals aged 20–81 from the Spanish Bladder Cancer Study, Spain No differences Menopause status Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Fetal Birthweight Michels et al., 2011 [53 ] LINE-1 Pyrosequencing 319 mother-child dyads from Brigham and Women’s Hospital, Boston Significant differences between low birthweight ( “Low birthweight, <2500 g” had a −0.82 change in LINE-1 methylation% and “High birthweight, 4000+ g” had a −0.43 change in LINE-1 methylation% Family history of breast cancer Brennan et al., 2012 [9 ] LINE-1 Pyrosequencing 769 individuals aged 23–83 from 3 cohorts, USA No differences Delgado-Cruzata et al., 2014 [54 ] LINE-1 MethyLight 333 unaffected women who had a sister with breast cancer from the Breast Cancer Family Registry, NY No differences Wu et al., 2011 [55 ] LINE-1 Pyrosequencing, MethyLight 51 girls aged 6–17, USA No differences Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Wu et al., 2011 [55 ] Alu MethyLight 51 girls aged 6–17, USA Significant differences ( Family history had 151.4 average Alu methylation% while no family history had 169.8 average Alu methylation% Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Age at Menarche Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Age at first birth Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Parity Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Hormone Cycle El-Maarri et al., 2011 [25 ] LINE-1 Pyrosequencing, SIRPH 500 individuals aged 18–64, Bonn, Germany No differences Sex Hormones Iwasaki et al., 2012 [56 ] LINE-1 LUMA 185 women aged 55–74, Japan No differences Ulrich et al., 2012 [57 ] LINE-1 Pyrosequencing 173 women aged 55–75 from the Physical Activity for Total Health Study No differences Hormone use Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences
