Table 3.

RRs for cancer risk within the highest versus lowest categories of iron (diet and biomarkers)

Exposure categories
Author, year, country (ref), study, and/or countryn casesMeasured variableLowestHighestComparisonUnitsAdjusted RR (95% CI)Ptrend
Colorectal
 A: Prospective
  Cross and colleagues (35);a NIH-AARP Diet and Health Study; USA2,719Heme iron48.1335.8Q5 vs. Q1mg/1,000 kcal1.13 (0.99–1.29)0.022
Dietary iron5.911.4Q5 vs. Q1mg/1,000 kcal0.75 (0.65–0.87)<0.001
Total iron10.836.1Q5 vs. Q1mg/d0.75 (0.66–0.86)<0.001
  Zhang and colleagues (36); Nurses' Health Study and Health Professionals Follow-up Study; USA2,114Heme iron (♀)<0.78>1.30Q5 vs. Q1mg/d1.10 (0.93–1.30)0.51
Heme iron (♂)<0.90>1.60Q5 vs. Q1mg/dCombined sex
Total iron (♀)<10.9>22.7Q5 vs. Q1mg/d1.09 (0.93–1.30)0.37
Total iron (♂)<12.6>24.6Q5 vs. Q1mg/dCombined sex
  Balder and colleagues (37); Netherlands Cohort Study; Netherlands1,535Heme iron (♂)0.60b1.85bQ5 vs. Q1mg/d1.16 (0.87–1.55)0.27
Heme iron (♀)0.47b1.54bQ5 vs. Q1mg/d1.22 (0.89–1.68)0.22
Total iron (♂)8.5b15bQ5 vs. Q1mg/d1.34 (0.93–1.93)0.12
Total iron (♀)9.5b17bQ5 vs. Q1mg/d1.08 (0.72–1.62)0.90
  Hara and colleagues (38); Japan Public Health Center-based Prospective Study; Japan1,284Heme iron (♂)0.24b0.77bQ4 vs. Q1mg/d1.06 (0.79–1.42)0.6
Heme iron (♀)0.23b0.67bQ4 vs. Q1mg/d0.88 (0.61–1.29)0.4
  Lee DH and colleagues (39);c Iowa Women's Health Study; USA741Heme iron (proximal colon)≤0.76≥2.05Q5 vs. Q1mg/d2.18 (1.24–3.86)0.01
Heme iron (distal colon)≤0.76≥2.05Q5 vs. Q1mg/d0.90 (0.45–1.81)0.77
  Kabat GC and colleagues (40); Canada617Heme iron<1.58≥2.95Q5 vs. Q1mg/d1.06 (0.80–1.42)0.99
Dietary iron<11.90≥14.99Q5 vs. Q1mg/d1.07 (0.80–1.43)0.94
  Larsson and colleagues (41);c Swedish Mammography Cohort; Sweden547Heme iron<0.67≥2.06Q5 vs. Q1mg/d1.31 (0.98–1.75)0.03
Heme iron (≥20 g/w alcohol)<0.67≥2.06Q5 vs. Q1mg/d2.29 (1.25–4.21)0.007
  Ekblom and colleagues (42); Northern Sweden Health and Disease Study225Plasma ferritin (full group)NANAQ5 vs. Q1μg/L0.48 (0.27–0.88)0.015
Serum TIBC (full group)NANAQ5 vs. Q1%2.24 (1.22–4.15)0.005
Plasma iron (age < 59 y)NANAQ5 vs. Q1μmol/L1.25 (0.57–2.72)0.35
Plasma iron (age ≥ 59 y)NANAQ5 vs. Q1μmol/L0.85 (0.45–1.62)0.91
Transferrin saturation (age < 59 y)NANAQ5 vs. Q1%1.02 (0.45–2.31)0.99
Transferrin saturation (age ≥ 59 y)NANAQ5 vs. Q1%0.46 (0.22–0.93)0.18
  Cross and colleagues (43); ATBC: α-tocopherol, β-carotene cancer prevention study cohort, Finland130Dietary iron≤14.4>22Q4 vs. Q1mg/d0.4 (0.1–1.1)0.06
Serum ferritin≤88>221Q4 vs. Q1ng/mL0.4 (0.2–0.9)0.09
Serum iron≤97>153Q4 vs. Q1μg/dL0.7 (0.3–1.5)0.41
Serum transferrin saturation≤29.7>47.3Q4 vs. Q1%0.6 (0.3–1.3)0.24
Serum TIBC≤300>351Q4 vs. Q1μg/dL1.4 (0.7–3.2)0.28
  Kato and colleagues (25); New York University Women's Health Study cohort; USA105Total ironNANAQ4 vs. Q1mg/d1.17 (0.6–2.3)0.44
Serum ironSerum ferritinNANANANAQ4 vs. Q1Q4 vs. Q1μg/dLng/mL0.85 (0.5–1.6)0.40 (0.2–0.8)0.52<0.01
Serum transferrin saturationNANAQ4 vs. Q1%0.63 (0.3–1.2)0.11
Serum TIBCNANAQ4 vs. Q1μg/dL1.81 (0.9–3.5)0.10
  Wurzelmann and colleagues (44); NHANES + NHEFS; USAc136Dietary ironNANAQ4 vs. Q1mg/d3.35 (1.74–6.46)<0.001
126Serum ironNANAQ4 vs. Q1μg/dL1.36 (0.77–2.41)0.24
 B: Case–control
  Sun and colleagues (46); Newfoundland, Labrador and Ontario; Canada1,760Total iron12.6b36.7bQ5 vs. Q1mg/d1.34 (1.01–1.78)0.02
  Levi and colleagues (45); Swiss Canton of Vaud, Switzerland223Dietary iron9.4b18bT3 vs. T1mg/d2.43 (1.2–5.1)<0.05
Breast
 A: Prospective
  Kabat and colleagues (50);a NIH-AARP Diet and Health Study; USA3,396Dietary iron<6.8≥10.1Q5 vs. Q1mg/1,000 kcal1.02 (0.90–1.15)0.94
Heme iron<62.9≥216.7Q5 vs. Q1μg/1,000 kcal1.01 (0.89–1.14)0.97
 Kabat and colleagues (51); Canada2,545Dietary iron<11.90≥14.99Q5 vs. Q1mg/d0.97 (0.85–1.10)0.63
Heme iron<1.58≥2.95Q5 vs. Q1mg/d1.03 (0.90–1.18)0.25
 Ferrucci and colleagues (52);a Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; USA1,205Dietary iron≤6.9>10.3Q5 vs. Q1mg/1,000 kcal1.25 (1.02–1.52)0.03
Heme iron (from meat)≤0.07>0.23Q5 vs. Q1mg/1,000 kcal1.12 (0.92–1.38)0.59
 B: Case–control
  Kallianpur AR and colleagues (53); Shanghai Endometrial Cancer Study; China3,452Dietary ironNANAQ4 vs. Q1NA1.32 (0.97–1.80)0.08
  Adzersen and colleagues (54); Heidelberg, Germany310Dietary iron<9.0>14.3Q4 vs. Q1mg/d0.66 (0.32–1.33)0.06
  Levi and colleagues (55); Swiss Canton of Vaud, Switzerland289Dietary iron9.0b16.8bT3 vs. T1mg/d1.21 (0.65–2.26)0.3
  Cade and colleagues (56); Southampton and Portsmouth, England220Dietary ironNANAQ4 vs. Q1NA0.49 (0.23–1.01)0.03
Gastric
 A: Prospective
  Jakzsyn and colleagues (59); EPIC-Europe; Europe444Heme iron0.36b1.97bQ4 vs. Q1mg/d1.67 (1.20–2.34)0.002
  Cook and colleagues (60); ATBC: α-tocopherol, β-carotene cancer prevention study cohort (a); Finland341Dietary irond<1.22≥1.53Q4 vs. Q1mg/1,000 kcal/d1.05 (0.60–1.85)0.931
Serum ferritin<96≥241Q4 vs. Q1ng/mL0.69 (0.44–1.09)0.108
Serum iron<92≥146Q4 vs. Q1μg/dL0.84 (0.53–1.33)0.463
Serum transferrin saturation<28.65≥44.10Q4 vs. Q1%0.92 (0.58–1.45)0.721
Serum TIBC<295≥362Q4 vs. Q1μg/dL0.91 (0.57–1.46)0.708
  Cross and colleagues (58);a NIH-AARP Diet and Health Study, USA532Heme iron (gastric cardia)48.8b347.7bQ5 vs. Q1μg/1,000 kcal0.83 (0.53–1.30)0.256
Heme iron (gastric non-cardia)48.8b347.7bQ5 vs. Q1μg/1,000 kcal0.72 (0.48–1.08)0.531
 B: Case–control
  Pelucchi and colleagues (61); Milan, Italy230Dietary ironNANAQ4 vs. Q1NA0.56 (0.27–1.15)0.10
  Corneé and colleagues (62); Marseille, France92Dietary ironNANAT3 vs. T1NA0.41 (0.19–0.89)0.02
  Ward and colleagues (63);a Nebraska, USA154Heme iron98 to <660>1,440Q4 vs. Q1μg/d1.99 (1.00–3.95)0.17
Dietary iron<10.6>17.3Q4 vs. Q1mg/d1.71 (0.75–3.18)0.21
Esophageal
 A: Prospective
  Cross and colleagues (58);a NIH-AARP Diet and Health Study, USA505Heme iron ESCCe48.8347.7Q5 vs. Q1μg/1,000 kcal1.25 (0.64–2.42)0.944
Heme iron EADCf48.8347.7Q5 vs. Q1μg/1,000 kcal1.47 (0.99–2.20)0.063
  Steffen and colleagues (68); EPIC-Europe; Europe151Heme iron ESCCe<116426–460Q5 vs. Q1μg/1,000 kcal0.99 (0.90–1.10)NA
B: Case–control
Ward and colleagues (63);a Nebraska, USA124Dietary iron<10.6>17.3Q4 vs. Q1mg/d1.67 (0.51–5.44)0.31
Heme iron98 to <660>1,440Q4 vs. Q1μg/d3.04 (1.20–7.72)0.01
O'Doherty and colleagues (26); FINBAR study, Ireland224Dietary iron<12.76≥15.44Q4 vs. Q1mg/d0.50 (0.25–0.98)0.06
Heme iron<0.74≥1.39Q4 vs. Q1mg/d3.11 (1.46–6.61)<0.01
Toenail iron<5.48≥11.52Q4 vs. Q1ppm0.40 (0.17–0.93)0.07
Lung
 A: Prospective
  Tasevska and colleagues (69);a NIH-AARP Diet and Health Study; USA6,361Heme iron (♂)≤90.2>285.2Q5 vs. Q1μg/1,000 kcal1.25 (1.07–1.45)0.02
Heme iron (♀)≤63.2>217.2Q5 vs. Q1μg/1,000 kcal1.18 (0.99–1.42)0.002
  Tasevska and colleagues (70);a Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; USA782Heme iron (♂)≤106>317Q5 vs. Q1μg/1,000 kcal0.91 (0.65–1.28)0.37
Heme iron (♀)≤72>227Q5 vs. Q1μg/1,000 kcal0.89 (0.62–1.29)0.78
  Lee DH and colleagues (71); Iowa Women's Health Study; USA700Heme iron (0 vit C)≤0.77≥2.44High vs. Low categoriesmg/d1.27 (0.67–2.40)0.75
Heme iron (>700 mg vit C)≤0.77≥2.44High vs. Low categoriesmg/d8.97 (1.29–62.51)0.02
  Zhou and colleagues (72); Massachusetts General Hospital, USA923Dietary iron≤10.76≥16.24Q5 vs. Q1mg/d1.45 (1.03–2.06)0.01

Abbreviation: NA, not available.

  • aHeme iron estimation according to NCI database (only meat food sources).

  • bMedian.

  • cColon cancer.

  • dmg/1,000 kcal/d.

  • eEsophageal squamous cell carcinoma.

  • fEsophageal adenocarcinoma.