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. 2016 Oct 19;6:35547. doi: 10.1038/srep35547

Table 1. Characteristics of studies on choline and betaine consumption and cancer risk.

First author year of publication (reference) Cancer type Country/design Cases/Controls Age(y)/sex Follow-up (y) Assessment of consumption/food item number/choline and betaine consumption calculation/nutrient database Contrast (highest vs lowest)
Ajusted OR/RR(95%CI) (highest vs lowest)
Matched or adjusted variables
Choline consumption only Betaine consumption only Choline plus Betaine consumption Choline consumption only Betaine consumtion only Choline plus Betiane consumption
Xu et al.6 Breast cancer USA; case-control (PB) 1,508/1,556 20-98 F NR FFQ/100/frequency × portion-size/USDA database Quintile >247.2 vs < 122.7mg/d Quintile >179.71vs < 61.11mg/d NR 0.85(0.61–1.18) 0.96(0.73–1.25) NR Age and daily energy intake
Ibiebele et al. 20107 Esophageal Cancer Australia; case-control (PB) 881/1,507 18-79 M/F NR FFQ/135/-/USDA database Quartile 1171 vs 380mg/d Quartile 185 vs 85mg/d NR EAC: 1.25(0.91–1.72) ESCC: 1.39(0.88–2.30) EAC: 0.79(0.58–1.07) ESCC: 1.30(0.83–1.99) NR Age, gender, education, BMI 1 y previously, frequency of heartburn or acid reflux 10 y prior to diagnosis, lifetime alcohol intake, pack-years of smoking, NSAID use, and total energy intake
Ying et al.8 Lung Cancer USA; case-control (HB) 2,821/2,923 no age restrictions M/F NR FFQ/214/frequency × nutrient content/USDA database Quartile (highest vs lowest) Quartile (highest vs lowest) NR 0.92(0.78–1.07) 0.71(0.61–0.84) NR Sex, race/ethnicity, age, pack-years, total caloric intake, family cancer history, dust exposure, second-hand smoke, emphysema, hay fever, smoking status, asthma, addiction index, alcohol, time since smoking cessation
Zeng et al.9 Nasopharyngeal Carcinoma China; case-control (HB) 600/600 30–75 M/F NR FFQ/78/frequency × portion-size/Chinese Food Composition Table Quartile 285 vs 125mg/d Quartile 539 vs 112mg/d Quartile 761 vs 285mg/d 0.42(0.29–0.61) 0.50(0.35–0.72) 0.44(0.30–0.64) Age, BMI, occupation, marital status, educational level, household income, current smoking, current drinking, exposure to potential toxic substances, multivitamin supplement, chronic rhinitis history, physical activity, dietary folate intake and daily energy intake
Zhang et al.10 Breast cancer China; two stage case-control (HB) stage 1: 438/438 stage 2: 369/369 Pooled: 807/807 25–70 F NR FFQ/81/frequency × portion-size/Chinese Food Composition Table stage 1: Quartile >207.86 vs < 111.64mg/d stage 2: Quartile >232.24 vs < 123.66mg/d Pooled: Quartile >217.47 vs < 117.65mg/d stage 1: Quartile >440.90 vs < 279.40 mg/d stage 2: Quartile >385.28 vs < 154.75 mg/d Pooled: Quartile >408.04 vs < 140.14 mg/d stage 1: Quartile >627.38 vs < 279.40 mg/d stage 2: Quartile >600.19 vs < 314.00 mg/d Pooled: Quartile >615.63 vs < 297.57 mg/d stage 1: 0.35(0.22–0.54) stage 2: 0.51(0.30–0.87) Pooled: 0.40(0.28–0.57) stage 1: 0.60(0.39–0.92) stage 2: 0.45(0.25–0.80) Pooled: 0.58(0.42–0.80) stage 1: 0.43(0.28–0.66) stage 2: 0.40(0.22–0.71) Pooled: 0.38(0.27–0.53) Occupation, body mass index, age at menarche, live births and age at first live birth, mother/sister/daughter with breast cancer, passive smoking, alcohol consumption, physical activity, total energy intake and study stage
Lu et al.11 Colorectal Cancer China; case-control (MB) 890/890 30–75 M/F NR FFQ/81/frequency × portion-size/Chinese Food Composition Table Quartile >176.40 vs < 99.68mg/d Quartile >323.10 vs < 116.70mg/d Quartile >535.50 vs < 224.70mg/d 0.54(0.37–0.80) 0.92(0.65–1.29) 0.91(0.65–1.28) Age, sex, residence, marital status, education, income level, occupation, family history of cancer, smoking status, passive smoking, alcohol drinking, degree of physical activity, BMI, red meat, fish, beans and folate intake
Cho et al.12 Breast cancer USA; cohort 1,032/89,631 26–46 F 12 FFQ/about 130/-/USDA database or other sources Quintile 397 vs 267mg/d Quintile 305 vs 114mg/d NR 0.88(0.72–1.07) 0.99(0.79–1.22) NR Smoking, height, parity and age at first birth, body mass index, age at menarche, family history of breast cancer, history of benign breast disease, oral contraceptive use, and intakes of alcohol, energy, and animal fat
Kotsopoulos et al.13 Epithelial ovarian cancer USA; cohort 526/159,431 25–55 F 22 FFQ/-/-/USDA database and other sources Quintile NHS:≥ 338.8 vs < 249.5 mg/d NHSII: ≥367.3 vs < 269.7 mg/d Quintile NHS: ≥127.3 vs < 70.5 mg/d NHSII: ≥138.9 vs >80.6 mg/d Quintile NHS: ≥453.8 vs < 339.8 mg/d NHSII: ≥491.7 vs < 371.6 mg/d 0.98(0.73–1.31) 0.98(0.74–1.31) 0.99(0.75–1.32) Age at menarche and parity, duration of oral contraceptive use, tubal ligation, height, family history of breast or ovarian cancer, caffeine intake, hysterectomy, PMH/menopausal status, caloric intake, alcohol consumption and BMI
Lee et al.14 Colorectal Cancer USA; cohort 987/46,315 40–75 M 18 FFQ/-/frequency × nutrient content/USDA database Quintile (highest vs lowest) Quintile (highest vs lowest) NR 0.97(0.79–1.20) 0.94(0.77–1.16) NR Total energy intake, aspirin dose, pack-years of smoking before age 30, body mass index, family history of colorectal cancer, history of endoscopy, alcohol intake, and total folate
Cho et al.15 Breast cancer USA; cohort 3,990/70,594 30–55 F 20 FFQ/about 130/frequency × nutrient content/Harvard University Food Composition Database and USDA database Quintile 396 vs 260mg/d Quintile 144 vs 71mg/d NR 1.10(0.99–1.22) 0.98(0.89–1.09) NR Smoking status, height, parity and age at first birth,body mass index at age 18, weight change between age 18 and current, physical activity, age at menarche, family history of breast cancer, history of benign breast disease, use of post-menopausal hormones, and intakes of alcohol, energy, and folate
Cho et al.16 Renal cell cancer USA; cohort NHS: 225/76,983 HPFS: 221/47,665 NHS: 30–55 F HPFS: 40–75 M F: 24 M: 22 FFQ/about 131/frequency × nutrient content/USDA database and other sources NHS: Quintile 399.8 vs 267.1mg/d HPFS: Quintile 471.7 vs 308.3mg/d Pooled: Quintile (highest vs lowest) NHS: Quintile 138.4 vs 70.5mg/d HPFS: Quintile 186.4 vs 84.9mg/d Pooled: Quintile (highest vs lowest) NR NHS: 0.78(0.48–1.27) HPFS: 0.96(0.62–1.48) Pooled: 0.87(0.63–1.21) NHS: 0.78(0.49–1.24) HPFS: 1.30(0.83–2.02) Pooled: 1.01(0.62–1.65) NR Age, smoking status, body mass index, history of hypertension, history of diabetes, physical activity, fruit intake, vegetable intake, and alcohol intake in NHS and HPFS and parity in NHS

Abbreviations: EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; FFQ, food frequency questionnaire; HB, hospital-based; HPFS, The Health Professionals Follow-up Study; PB, population-based; MB, mixed based (including both hospital-based and population-based); NASID, Non-steroidal Anti-inflammatory Drugs; NHS, The Nurses’ Health Study; NHSII, The Nurses’ Health Study II; NR, no record; PMH, postmenopausal hormone; USDA, US Department of Agriculture.