. 2016 May 4;74(6):353–373. doi: 10.1093/nutrit/nuw003

Table 2.

Cohort studies evaluating whole-grain consumption in relation to cancer risk^a

Reference	Location	Sample (n)	Outcome	Contrast	RR/HR (95% CI)	Covariates
Female cancers
Kasum et al. (2001)²⁵	USA; Iowa Women’s Health Study	23,014 postmenopausal women Age: 55–69 y Follow-up: 13 y	Endometrial cancer 382 cases	Whole-grain intake: Quintile 5 vs 1 (18.5–108 vs 0–3.5 servings/wk)	0.89 (0.61–1.29); P_trend = .24	Age, energy, education, BMI, smoking, vitamin use, fruits and vegetables, red meat, refined/whole grain, total fat, saturated fat, age at menarche, age at menopause, number of live births, and HRT
Nicodemus et al. (2001)²⁷	USA; Iowa Women’s Health Study	29,119 menopausal women Age: 55–69 y Follow-up: 9 y	Breast cancer 977 cases	Whole-grain intake: Quintile 5 vs 1 (19–108.5 vs 0–3.5 servings/wk)	1.21 (0.96–1.5); P_trend = .02	Age, energy, HRT, history of benign breast disease, family history of breast cancer, mammography status, age at first live birth, number of live births, weight, waist-to-hip ratio, vitamin use, education, vitamin A, and refined/whole grain
Fung et al. (2005)²⁸	USA; Nurses Health Study	71,058 postmenopausal women Age: 30–55 y Follow-up: 16 y	Breast cancer 512 ER⁻ cases	Whole-grain servings: Frequency of consumption (2–3.9/d vs <1/wk) Per serving increase	1.04 (0.63–1.69); P_trend = .77 0.99 (0.91–1.07)	Age, smoking status, BMI, multivitamin use, energy, physical activity, family history of breast cancer, history of benign breast disease, duration of menopause, age at menopause, HRT, age at menarche, parity, age at first birth, BMI at age 18, weight change since age 18, adult height, and alcohol
Egeberg et al. (2009)³⁰	Denmark; Diet, Cancer and Health Cohort Study	25,278 postmenopausal women Age: 50–64 y Follow up (mean): 9.6 y	Breast cancer 978 cases Follow-up (mean): 9.6 y	Whole-grain product intake: Quartile 4 vs 1 (>163 vs <72 g/d) Per each 50 g/d increment	1.03 (0.85–1.24); P_trend = N/A 1.01 (0.96–1.07)	Parity, age at first birth, education, HRT, duration of HRT use, alcohol, and BMI
Aarestrup et al. (2012)²⁶	Denmark; Diet, Cancer and Health Cohort	24,418 postmenopausal women Age: 50–64 y	Endometrial cancer 217 cases	Whole-grain intake: Quartile 4 vs 1 (>52 vs <25 g/d) Per 25 g increment Whole-grain product intake: Quartile 4 vs 1 (>52 vs <25 g/d) Per 50 g increment	1.08 (0.71–1.65); P_trend = N/A 1.00 (0.99–1.01) 1.08 (0.71–1.65); P_trend = .83 1.01 (0.89–1.15)	Menopausal status, HRT, HRT type, parity, age at first pregnancy, BMI, smoking, and energy
Genitourinary cancers
Egeberg et al. (2011)²⁹	Denmark; Diet, Cancer and Health Cohort Study	26,691 men Age: 50–64 y Follow-up (median): 12.4 y	Prostate cancer1081 cases	Whole-grain product intake: Quartile 4 vs 1 (>200 vs <103 g/d) Per 50 g increment	1.06 (0.89–1.26) 1.00 (0.96–1.05)	Height, weight, education, red and processed meat, dairy products, and smoking
Nimptsch et al. (2011)³³	USA; Health Professionals Follow-up Study	49,934 men Age: 40–75 y Follow up: 1986–2007	Prostate cancer 5112 cases	Whole-grain intake: Quintile 5 vs 1 (>34.3 vs <6.5 g/d)	1.13 (1.03–1.24); P_trend = .001	BMI, height, history of diabetes, family history of prostate cancer, race/ethnicity, smoking, vigorous physical activity, energy, alcohol, calcium, alpha-linolenic acid, and tomato sauce
Drake et al. (2012)³⁴	Sweden; Malmo Diet and Cancer Cohort	8128 men Age: 45–73 y Follow-up: 15 y (median)	Prostate cancer 817 cases	Whole-grain intake: Quintile 5 vs 1 (median intake: 51.5 vs 0 g/d)	1.00 (0.78–1.28); P_trend = .803	Age, year of study entry, season of data collection, energy, height, waist, physical activity, smoking, educational, birth in Sweden, alcohol, calcium, selenium, competing risk by death from all causes except prostate cancer
Daniel et al. (2013)⁴⁰	USA; NIH–AARP Diet and Health Study	491,841 men and women Age: 50–71 y Follow-up (mean): 9 y	Renal cell carcinoma 1816 cases	Whole-grain intake: Quintile 5 vs 1 (median intake: 1.1 vs 0.13 servings/1000 kcal)	0.84 (0.73–0.98); P_trend = .05	Age, sex, education, race, marital status, family history of any cancer, BMI, smoking, hypertension, diabetes, alcohol, red meat, energy, fruits, vegetables, legumes
Gastrointestinal cancers
Kasum et al. (2002)⁴¹	USA; Iowa Women’s Health Study	34,651 postmenopausal women Age: 55–69 y Follow-up: 14 y	Upper aerodigestive tract cancer 169 cases	Whole-grain intake: Tertile 3 vs 1 (13–108.5 vs 0–6.5 servings/wk)	Upper aerodigestive tract cancers: 0.53 (0.34–0.81); P_trend = .005 Esophageal cancer^a: 0.47 Gastric cancer^a: 0.61	Age, smoking, alcohol, and energy
McCullough et al. (2003)³⁵	USA; Cancer Prevention Study II Nutrition Cohort	62,609 men 70,554 women Age: 50–74 y	Colorectal cancer 508 cases	Whole-grain intake: Quintile 5 vs 1 (>11 vs <2 servings/wk)	Men: 0.95 (0.64–1.42); P_trend = .78 Women: 1.17 (0.73–1.87); P_trend = .52	Age, physical activity, aspirin, smoking, family history of colorectal cancer, BMI, education, energy, multivitamin use, total calcium, red meat, and HRT
Wu et al. (2004)³⁶	USA; Health Professionals Follow-up Study	47,311 men Age: 45–75 y Follow-up: 14 y	Colorectal cancer 561 cases	Whole-grain intake: Quintile 5 vs 1	0.75 (0.57–1.00); P_trend = N/A	Age, family history of colorectal cancer, history of endoscopy, physical activity, smoking before age 30, race, aspirin use, and energy
Larsson et al. (2005)³⁷	Sweden; Swedish Mammography Cohort	61,433 women Mean age: 53–55 y Mean follow-up: 14.8 y	Colorectal cancer 805 cases	Whole-grain intake: ≥4.5 vs <1.5 servings/d	Colorectal cancer: 0.80 (0.60–1.06); P_trend = .16 Colon cancer: 0.67 (0.47–0.96); P_trend = .06 Rectal cancer: 1.11 (0.67–1.83); P_trend = .85	Age, BMI, education, energy, saturated fat, calcium, red meat, fruits, and vegetables
Schatzkin et al. (2007)⁴²	USA; NIH–AARP Diet and Health Study	291,988 men and 197,623 women Age: 50–71 y Follow-up: 1995–2000	Colorectal cancer 2974 cases	Whole-grain intake: Quintiles 5 vs 1 (median intake: 5.7 vs 1.7 g/1000 kcal/d)	0.79 (0.70–0.89); P_trend < .001	Sex, physical activity, smoking, menopausal status, HRT, red meat, dietary calcium, dietary folate, and energy
Schatzkin et al. (2008)³⁸	USA; NIH–AARP Diet and Health Study	291,988 men and 197,623 women Age: 50–71 y Follow-up: 1995–2003	Small intestinal cancer 165 cases	Whole-grain intake: Quintiles 5 vs 1 (1.4 vs 0.2 servings/1000 kcal/d)	0.59 (0.33–1.05); P_trend = .06	Age, sex, education, family history of cancer, smoking, BMI, physical activity, HRT, red meat, total fat, energy, and fiber
Egeberg et al. (2010)⁴⁴	Denmark; Diet, Cancer and Health Cohort Study	26,630 men and 29,189 women Age: 50–64 y Follow up (median): 10.6 y	Colorectal cancer 461 colon cancer cases 283 rectal cancer cases Follow-up (median): 10.6 y	Whole-grain product intake: Quartile 4 vs 1 (>160 vs <75 g/d) Per 50 g increment	Colon cancer: Men: 0.61 (0.43–0.86) Women: 0.92 (0.63–1.35); P_trend = N/A Rectal Cancer: Men: 0.88 (0.57–1.36) Women: 0.81 (0.50–1.30); P_trend = N/A Colon cancer: Men: 0.85 (0.77–0.94) Women: 0.98 (0.88–1.10) Rectal cancer: Men: 0.90 (0.80–1.01) Women: 1.02 (0.88–1.19)	BMI, alcohol, education, red and processed meat, HRT, and leisure time physical activity
Fung et al. (2010)⁴³	USA; Health Professionals Follow-up Study Nurses Health Study	45,490 men Age: 40–75 y Follow-up: 20 y 87,256 women Age: 34–59 y Follow-up: 26 y	Colorectal cancer 1032 cases among men 1432 cases among women	Whole-grain intake: Per additional serving/d	Men: 0.94 (0.88–0.99) Women: 0.95 (0.89–1.02)	Age, BMI, alcohol, family history of colorectal cancer, physical activity, aspirin, colonoscopy, history of polyps, smoking, energy, and multivitamin use
Kyro et al. (2013)³¹	Scandinavia (Denmark, Sweden, Norway)	108,000 men and women Age: 40–55 y Follow-up: 11 y (median)	Colorectal cancer 1123 cases	Total whole-grain intake: Quartile 4 vs 1 (>71 vs <31 g/d in males and >68 vs <30 g/d in females) Per 25 g increase	0.86 (0.69–1.06); P_trend = .11 0.94 (0.88–1.01)	Alcohol. smoking, education, HRT, red and processed meat, BMI, energy, and other grain products
Head and neck cancers
Kasum et al. (2002)⁴¹	USA; Iowa Women’s Health Study	34,651 postmenopausal women Age: 55–69 y Follow-up: 14 y	Upper aerodigestive tract cancer 169 cases	Whole-grains intake (servings/wk): Tertile 3 vs 1 (13–108.5 vs 0–6.5 servings/wk)	Upper aerodigestive tract cancers: 0.53 (0.34–0.81); P_trend = .005 Oral/pharangeal^a: 0.47 Nasopharangeal/salivary^a: 0.67 Laryngeal^a: 0.44	Age, smoking, alcohol, and energy
Lam et al. (2011)³⁹	USA; NIH–AARP Diet and Health Study	494,991 men and women Age: 50–71 Follow-up:11 y	Head and neck cancers 1867 cases	Whole-grain intake: Quintile 5 vs 1 (median intake: 1.1 vs 0.15 servings/1000 kcal) Quintile 5 vs 1 (median intake: 1.1 vs 0.12 servings/1000 kcal)	Women: 0.71 (0.51–0.97); P_trend = .005 Men: 0.85 (0.72–1.01); P_trend = .139	Energy, education, BMI, physical activity, alcohol, smoking dose, red meat, and fiber
Hematologic cancers
Thompson et al. (2010)³²	USA; Iowa Women’s Health Study	35,159 postmenopausal women Age: 55–69 y Follow-up: 19 y	Non-Hodgkin’s lymphoma 415 cases	Whole-grain intake: >17 vs <4.6 servings/wk	0.88 (0.66–1.17)	Age and energy

^a Dietary intakes of whole grains were measured using a food frequency questionnaire in all studies except the study by Drake et al. (2012)³⁴, where a 7-day menu book and 1-hour dietary interview were also used.

^b These hazard ratios do not have an associated confidence interval due to the small number of site-specific cancer cases, which limited statistical testing.

Abbreviations: BMI, body mass index; CI, confidence interval; ER, Estrogen Receptor; HR, hazard ratio; HRT, hormone replacement therapy; N/A, Not Applicable; NIH–AARP, National Institutes of Health–American Association of Retired Persons; PR, Progesterone Receptor; RR, relative risk.