| | Study | Country | Year | Study design | Source of controls | Recruitment period | Cancer | Sex | Case/control |
Distribution of MTHFR C677T genotype in controls | HWE (yes/no) |
Distribution of MTHFR A1298C
genotype in controls | HWE (yes/no) | Adjustments | | CC (%) | CT (%) | TT (%) | | AA (%) | AC (%) | CC (%) |
| | Park et al. [34] | South Korea | 1999 | Case control | Healthy persons | Not reported | CRC | Both | 200/460 | 30.4 | 53.5 | 16.1 | No | | | | | Calculated OR, no adjustments |
| | Delgado-Enciso et al. [15] | Mexico | 2001 | Case control | Not reported | 1997 | CRC | Both | 74/110 | 30.9 | 47.3 | 21.8 | Yes | | | | | Calculated OR, no adjustments |
| | Keku et al. [35] | USA | 2002 | Case control | Healthy persons | 1996–2000 | Colon-Cauc | Both | 555/875 | 49.2 | 41.4 | 9.4 | Yes | 52.5 | 38.5 | 9.3 | Yes | Adjusted for sampling fraction, age, gender, and energy intake |
| | Le Marchand et al. [23] | USA | 2002 | Matched case control | Healthy persons | 1994–1998 | CRC | Both | 727/727 | 39.2 | 45 | 15.8 | Yes | 58.2 | 36.0 | 5.8 | No | Adjusted for age, gender, ethnicity, pack years of cigarette smoking, lifetime recreational physical activity, lifetime aspirin use, BMI 5 years ago, years of schooling, and intakes of nonstarch polysaccharides from vegetables and calcium from foods and supplements |
| Matsuo
et al. [16] | Japan | 2002 | Case control | Hospital patients | 1999 | CRC
colon
rectal | Both | 142/241
72/241
70/241 | 33.6 | 51.5 | 14.9 | Yes | 65.1 | 31.1 | 3.7 | Yes | Adjusted for age |
| Shannon
et al. [36] | Australia | 2002 | Case control | Healthy persons | 1985–1998 | CRC | Both | 501/
1,207 | 44.2 | 46.4 | 9.4 | Yes | | | | | Calculated OR, no adjustments |
| Plaschke
et al. [37] | Germany | 2003 | Case control | Healthy persons | Not reported | CRC | Both | 287/346 | 43.1 | 45.9 | 11 | Yes | 44.5 | 43.6 | 11.8 | Yes | Adjusted for gender |
| Pufulete
et al. [38] | United Kingdom | 2003 | Case control | Hospital patients | 2000-2001 | CRC | Both | 304/352 | 54 | 38 | 8 | Yes | 61.8 | 34.2 | 3.9 | Yes | Adjusted for age, gender, BMI, smoking, and ROH intake. |
| Toffoli
et al. [39] | Italy | 2003 | Case control | Healthy persons | 1999-2000 | Colon | Both | 276/279 | 29.7 | 50.2 | 20.1 | Yes | 47.7 | 43.4 | 9 | Yes | Calculated OR, no adjustments |
| | Jiang et al. [40] | China | 2004 | Case control | Healthy person | 1990–2002 | CRC | Both | 126/343 | 39.1 | 42.4 | 18.5 | No | 67.6 | 30.7 | 1.8 | Yes | Adjusted for age and sex |
| | Miao et al. [41] | China | 2005 | Case control | Healthy persons | 1999–2002 | CRC | Both | 198/420 | 31.7 | 47.9 | 20.5 | Yes | 67.1 | 31.4 | 1.4 | No | None reported |
| | Ulvik et al. [20] | Norway | 2004 | Nested case control | Healthy persons | 1992-1991 | CRC | Both | 2,168/
2,168 | 49.9 | 40.4 | 9.7 | Yes | | | | | Adjusted for age and gender |
| | Yin et al. [21] | Japan | 2004 | Case control | Hospital patients | 2000–2003 | CRC | Both | 685/778 | 35.7 | 47.2 | 17.1 | Yes | 66.2 | 31.4 | 2.4 | Yes | Adjusted for gender. 5-year age class, area and alcohol use |
| Jiang
et al. [42] | China | 2005 | Nested case control | Healthy persons | 1989-1990 | Colon
rectal | Both | 52/338
72/338 | 39.5 | 42.2 | 18.3 | No | 67.5 | 30.7 | 1.8 | No | Adjusted for gender, age, folate, methionine, total energy intake, smoking status, and drinking status |
| | Landi et al. [43] | Spain | 2005 | Case control | Hospital patients | 1996–1998 | CRC | Both | 359/320 | 35.3 | 45 | 19.7 | Yes | 53.3 | 39.8 | 6.9 | Yes | Adjusted for age and sex |
| Matsuo
et al. [44] | Japan | 2005 | Matched case control | Hospital patients | 2001–2004 | CRC | Both | 257/771 | 37.5 | 45.1 | 17.3 | Yes | 62.5 | 33.5 | 4.0 | Yes | Adjusted for age, sex, referral patterns, smoking BMI, physical, exercise and family history of CRC |
| | Otani et al. [45] | Japan | 2005 | Matched case control | Hospital patients | 1998–2002 | CRC | Both | 107/224 | 23 | 51.4 | 25.6 | Yes | 69.6 | 28.1 | 2.2 | Yes | Matching factors and adjusted for smoking, alcohol consumption, BMI, and total dietary fiber intake |
| Le Marchand
et al. [46] | USA
(Hawaii and California) | 2005 | Nested case control | Healthy persons | 1993–1996 | CRC
colon
rectal | Both | 822/
2,021 | 48.9 | 38.5 | 12.6 | No | | | | | Adjusted for age, gender, and ethnicity |
| |
Battistelli et al. [47] | Italy | 2006 | Case control | Healthy controls | Not reported | CRC | Both | 93/100 | 30 | 51 | 29 | Yes | | | | | Calculated OR, no adjustments |
| Van Guelpen
et al. [24] | Sweden | 2006 | Nested case control | Healthy persons | 1985–2002 | CRC | Both | 226/437 | 52.8 | 38.7 | 8.5 | Yes | 45.9 | 42.0 | 12.1 | Yes | Adjusted for BMI, smoking, recreational and occupational physical activity, and alcohol intake |
| | Wang et al. [48] | India | 2006 | Case control | Healthy persons | 1999–2001 | CRC
colon
rectal | Both | 435/340 | 87.6 | 12.4 | 0 | Yes | 36.1 | 46.4 | 17.5 | Yes | Adjusted for gender, age household income, education, religion, mother tongue, smoking, drinking, chewing, and vegetarianism |
| Lima
et al. [49] | Brazil | 2007 | Case control | Healthy persons | 1999–2001 | CRC | Both | 102/300 | 47.7 | 42.3 | 10 | Yes | 63.7 | 31.0 | 5.3 | Yes | Adjusted for age, gender, and race |
| Chang
et al. [50] | Taiwan | 2007 | Matched case control | Hospital patients | 2000-2001 | CRC | Both | 195/195 | 47.2 | 44.6 | 8.2 | Yes | 61.5 | 33.3 | 5.1 | Yes | Matched on age and gender. |
| Curtin
et al. [51] | USA | 2007 | Matched case control | Healthy persons | 1991–1994 | Colon | Both | 916/
1,972 | 45.0 | 43.5 | 11.5 | Yes | 47.1 | 41.9 | 11 | Yes | Calculated OR, no adjustments |
| | Hubner et al. [52] | United Kingdom | 2007 | Case control | Healthy controls | Not reported | CRC | Both | 1,685/
2,695 | 43.6 | 44.3 | 12.1 | Yes | | | | | Adjusted for age, sex, family history, cancer location, stage, and grade |
| | Jin et al. [53] | China | 2007 | Case control | Healthy controls | 2002–2005 | CRC | Both | 449/672 | 31.4 | 48.4 | 20.2 | Yes | | | | | Adjusted for age, sex, drinking, BMI, smoking, and family history |
| Murtaugh
et al. [54] | USA | 2007 | Matched case control | Healthy persons | 1997–2001 | Rectal-Men
Rectal-Women | Both
Men
Women | 751/979 | 48.2
47.5 | 40.1
41.4 | 11.7
11.1 | No | 44.9 | 43.7 | 11.3 | Yes | Adjusted for age, BMI, activity, energy, fiber, calcium, ibuprofen use, smoking, and other MTHFR genotype |
| | Osian et al. [55] | Romania | 2007 | Matched case control | Hospital patients | 2003–2005 | CRC | Both | 69/67 | 70.2 | 25.4 | 4.5 | Yes | 61.1 | 37.3 | 1.5 | Yes | Matched on age and sex |
| Zeybek
et al. [17] | Turkey | 2007 | Case control | Hospital patients | 2003–2005 | CRC | Both | 52/144 | 44.4 | 45.1 | 10.4 | Yes | | | | | Calculated OR, no adjustments |
| | Cao et al. [56] | China | 2008 | Matched case control | Healthy persons | 2000–2002 | CRC | Both | 315/371 | 32.7 | 49.5 | 17.8 | Yes | 64.4 | 32.1 | 3.5 | Yes | Matched on ethnicity, sex, and age |
| |
Küry et al. [57] | France | 2008 | Matched case control | Healthy persons | 2002–2006 | CRC | Both | 1,023/1,121 | 40.8 | 45.9 | 13.3 | Yes | 51.5 | 39.5 | 9 | Yes | Matched on age and sex |
| Lightfoot
et al. [58] | United Kingdom | 2008 | Matched case control | Hospital patients | 1997–2000 | CRC | Both | 468/734 | 45.8 | 46 | 8.3 | Yes | 48.6 | 43.7 | 7.8 | Yes | Adjusted for gender and age |
| Mokarram
et al. [59] | Iran | 2008 | Case control | Not reported | 2003–2005 | Colon | Both | 151/81 | 49.4 | 38.3 | 12.3 | Yes | | | | | Calculated OR, no adjustments |
| Sharp
et al. [60] | United Kingdom
(Scotland) | 2008 | Matched case control | Healthy persons | 1998–2000 | CRC | Both | 264/408 | 43.2 | 44.9 | 11.9 | Yes | 44.9 | 39.8 | 15.2 | No | Adjusted for age, gender, family history of CRC, physical activity, NAAID use, total energy intake, and type of dietary supplements |
| Theodoratou
et al. [61] | Scotland | 2008 | Case control | Healthy persons | 1999–2006 | CRC | Both | 2,028/
2,722 | 45.3 | 45.0 | 11.5 | Yes | 45.8 | 44.1 | 10.1 | Yes | Adjusted for age, sex, deprivation score, and family history risk |
| Zhang
et al. [62] | China | 2008 | Matched case control | Hospital patients | 2003–2005 | CRC | Both | 300/300 | 30.4 | 46.5 | 23.1 | Yes | 65.3 | 29.7 | 5 | Yes | Adjusted for age, sex, education, family history, smoking, and drinking. |
| El Awady
et al. [63] | Egypt | 2009 | Case control | Healthy persons | 2004–2007 | CRC | Both | 35/68 | 65 | 29 | 6 | Yes | 38 | 54 | 8 | Yes | None reported |
| Gallegos-Arreola
et al. [30] | Mexico | 2009 | Case control | Healthy persons | 2006–2008 | CRC | Both | 369/170 | 33.6 | 34.1 | 32.2 | No | | | | | Calculated OR, no adjustments |
| Haghighi
et al. [22] | Iran | 2009 | Case control | Hospital patients | 2004–2007 | CRC | Both | 234/257 | 36.6 | 31.1 | 32.3 | Yes | | | | | None reported |
| Iacopetta
et al. [18] | Australia | 2009 | Matched case control | Healthy persons | 2005–2007 | Proximal distal CRC | Both | 850/958 | 45 | 45 | 10 | Yes | | | | | Matched on gender, age, socioeconomic status, country of birth, educational level, and smoking status |
| Chandy
et al. [14] | India | 2010 | Matched case control | Healthy persons | 2006–2008 | CRC | Both | 100/86 | 76.7 | 22.1 | 1.2 | Yes | 25.6 | 58.1 | 16.3 | Yes | Matched on age and gender |
| | Cui et al. [28] | South Korea | 2010 | Case control | Hospital patients | 2004–2008 | CRC | Both | 1,829/
1,700 | 31.8 | 50.7 | 17.5 | Yes | | | | | Adjusted for age and sex |
| | Eussen et al. [64] | EPIC | 2010 | Nested case control | Healthy persons | 1992–1998 | CRC | Both | 1,367/
2,325 | 43.1 | 45.5 | 11.5 | Yes | 46.5 | 42.6 | 11.0 | Yes | Calculated OR, no adjustments |
| |
Fernández-Peralta et al. [65] | Spain | 2010 | Matched case control | Healthy persons | 1992–1996 | CRC | Both | 143/103 | 42.7 | 48.6 | 8.7 | Yes | 55.3 | 42.7 | 1.9 | No | Matched on age and sex |
| Karpinski
et al. [66] | Poland | 2010 | Case control | Healthy persons | Not reported | CRC | Both | 186/140 | 51 | 39 | 10 | Yes | | | | | Adjusted for age and sex |
| |
Komlósi et al. [67] | Hungary | 2010 | Case control | Healthy persons | 2001–2007 | Colon
rectal | Both
Both | 476/461
479/478 | 47
47 | 40
41 | 13
12 | Yes
Yes | | | | | Adjusted for sex, age, and BMI
Adjusted for sex, age, and BMI |
| Naghib alhossaini
et al. [68] | Iran | 2010 | Case control | Not reported | Not reported | CRC | Both | 151/230 | 42.4 | 53 | 4.6 | Yes | 42.5 | 45.7 | 11.8 | Yes | Adjusted for age, sex, and smoking status |
| Promthet
et al. [69] | Thailand | 2010 | Matched case control | Healthy persons | 2002–2006 | Colon | Both | 130/130 | 72.3 | 23.8 | 3.9 | Yes | 41.5 | 54.6 | 3.9 | No | Matched on age and sex |
| Wettergren
et al. [70] | Sweden | 2010 | Case control | Healthy persons | 1994–2004 | CRC | Both | 181/300 | 55.9 | 35.8 | 8.4 | Yes | | | | | Calculated OR, no adjustments |
| | Abuli et al. [71] | Spain | 2011 | Matched case control | Healthy person | 2000-2001 | CRC | Both | 515/515 | 38.1 | 48 | 13.9 | Yes | | | | | Matched on age and sex |
| |
Guimarães et al. [72] | Brazil | 2011 | Case control | Healthy persons | 1992–2003 | CRC | Both | 113/188 | 48.9 | 42.0 | 9 | Yes | 67.6 | 26.1 | 6.4 | No | Adjusted for age, sex, and ethnic origin |
| |
Jokić et al. [73] | Croatia | 2011 | Case control | Healthy persons | Not reported | Colon | Both | 300/300 | 47.3 | 43.3 | 9.3 | Yes | 46.7 | 42.7 | 10.6 | Yes | |
| Pardini
et al. [25] | Czech Republic | 2011 | Case control | Hospital patients | 2004–2006 | CRC | Both | 666/
1,377 | 44.5 | 45.6 | 9.9 | Yes | 42.3 | 46.3 | 11.3 | Yes | Adjusted for age and gender |
| | Kim et al. [26] | South Korea | 2011 | Case control | Hospital patients | Not reported | CRC | Both | 67/53 | 28.3 | 39.6 | 32.1 | Yes | 67.9 | 30.2 | 1.9 | Yes | None reported |
| Sameer
et al. [74] | Kashmiri
(India) | 2011 | Matched case control | Healthy persons | 2008-2009 | CRC | Both | 86/160 | 75.6 | 16.9 | 7.5 | No | | | | | None reported |
| |
Prasad and Wilkhoo [75] | India | 2011 | Case control | Healthy person | Not reported | CRC | Both | 110/241 | 94.6 | 5.0 | 0.4 | Yes | | | | | None reported |
| | Zhu et al. [29] | China | 2011 | Case control | Healthy persons | 2006–2008 | CRC | Both | 86/100 | 49.0 | 41.0 | 10 | Yes | | | | | None reported |
| | Kim et al. [27] | South Korea | 2012 | Case control | Hospital patients | 1998–2004 | CRC | Both | 787/656 | 31.3 | 44.1 | 24.7 | No | | | | | Adjusted for age, sex, family history, multivitamin use, BMI, smoking status, and total energy |
| | Lee et al. [76] | USA | 2012 | Nested case control | Healthy persons | Health professionals follow-up study | CRC | Men | 173/345 | 44 | 39.9 | 16 | Yes | 47.7 | 42.6 | 10.3 | Yes | RR’s reported, so OR’s are calculated, no adjustments |
| | Lee et al. [76] | USA | 2012 | Nested Case Control | Healthy persons | Physicians’ health study | CRC | Men | 240/408 | 47.7 | 37.2 | 15 | Yes | 45.8 | 42.2 | 12.1 | Yes | RR’s reported, so OR’s are calculate, no adjustments |
| | Lee et al. [76] | USA | 2012 | Nested Case Control | Healthy persons | Nurse Health Study | CRC | Women | 189/377 | 46.7 | 39.7 | 13.6 | Yes | 51 | 38.3 | 10.7 | Yes | RR’s reported, so OR’s are calculated no adjustments |
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