Baseline characteristics of the Nurses' Health Study cohort^*.

<p>*Dietary intake and other characteristics at baseline questionnaire in 1980 (mean value, unless otherwise indicated).</p>Ψ<p>All values have been directly standardized according to the age distribution of the cohort.</p>†<p>Pack-years were calculated for former and current smokers only.</p>‡<p>The body-mass index is the weight in kilograms divided by the square of the height in meters.</p>§<p>METS are metabolic equivalents. This was calculated based on the frequency of physical activities (such as jogging) in 1986.</p

Risk of colon cancer according to baseline quintiles of one-carbon nutrient intake by CIMP expression in tumors among 88,691 women in the Nurses' Health Study (1980–2002).

‡<p>Age adjusted only.</p><p>*All models are adjusted for age (continuous), energy intake, gender, screening sigmoidoscopy, family history of colorectal cancer, aspirin use, smoking, physical activity in METs, baseline body mass index, a history of colon polyps, beef intake, calcium, multi-vitamin use, and baseline folate, vitamin B6, B12, methionine, and alcohol if not primary exposure. P for heterogeneity of the association for folate intake and CIMP-low/0 colon cancer versus folate intake and CIMP-high colon cancers = 0.73 (χ² = 1.31, 3 d.f.).</p><p>P for heterogeneity of the association for vitamin B₆ intake and CIMP-high colon cancer and vitamin B₆ intake and CIMP-low/0 colon cancers = 0.63 (χ² = 2.6, 4 d.f.) and for vitamin B₁₂ intake = 0.94 (χ² = 0.79, 4 d.f.). P for heterogeneity of the association for methionine intake and CIMP-high colon cancer and methionine intake and CIMP-low/0 colon cancers = 0.007 (χ² = 14.097, 4 d.f.), and for alcohol intake = 0.32 (χ² = 3.52, 3 d.f.).</p

Risk of colon cancer according to baseline quintiles of one-carbon nutrient intake by BRAF mutation status in tumors among 88,691 women in the Nurses' Health Study (1980–2002).

‡<p>Age adjusted only.</p><p>*All models are adjusted for age (continuous), energy intake, gender, screening sigmoidoscopy, family history of colorectal cancer, aspirin use, smoking, physical activity in METs, baseline body mass index, a history of colon polyps, beef intake, calcium, multi-vitamin use, and baseline folate, vitamin B₆, B₁₂, methionine, and alcohol if not primary exposure.</p

The relative risks of fatal colorectal cancer according to lifetime number of blood donations in the Health Professionals Follow-up Study (1992–2008).

1<p>adjusted for age (in months).</p>2<p>adjusted for age (in months), smoking before age 30 (0, 1–4, 5–10, or >10 pack-years), history of colorectal cancer in a parent or sibling (yes, no), history of colonoscopy or sigmoidoscopy (yes, no), regular aspirin use (yes, no), body mass index (<25, 25–<30, ≥30 kg/m²), physical activity (<3, 3–<27, ≥27 MET-hrs/wk).</p>3<p>adjusted for age (in months), factors listed in model 2, consumption of processed meat (quintiles), consumption of beef, pork, or lamb as a main dish (quintiles), alcohol consumption (0–<5, 5–<10, 10–<15, or ≥15 g/d), multivitamin use (yes, no), energy-adjusted total calcium intake (quintiles), total folate intake (quintiles), and total vitamin D intake (quintiles).</p

The relative risks of colorectal cancer and sub-sites according to lifetime number of blood donations in the Health Professionals Follow-up Study (1992–2008).

1<p>adjusted for age (in months).</p>2<p>adjusted for age (in months), smoking before age 30 (0, 1–4, 5–10, or >10 pack-years), history of colorectal cancer in a parent or sibling (yes, no), history of colonoscopy or sigmoidoscopy (yes, no), regular aspirin use (yes, no), body mass index (<25, 25–<30, ≥30 kg/m²), physical activity (<3, 3–<27, ≥27 MET-hrs/wk).</p>3<p>adjusted for age (in months), factors listed in model 2, consumption of processed meat (quintiles), consumption of beef, pork, or lamb as a main dish (quintiles), alcohol consumption (0–<5, 5–<10, 10–<15, or ≥15 g/d), multivitamin use (yes, no), energy-adjusted total calcium intake (quintiles), total folate intake (quintiles), and total vitamin D intake (quintiles).</p

Age-standardized risk factors for colorectal cancer in relation to lifetime number of blood donation in the Health Professionals Follow-up Study.

1<p>Body mass index was calculated as weight in kilograms divided by the square of height in meters.</p>2<p>MET denotes metabolic equivalent. MET-hours  =  sum of the average time/week spent in each activity x MET value of each activity.</p>3<p>Regular aspirin user was defined as consumption of 2 or more 325-mg tablets per week. Non-regular user was defined otherwise.</p>4<p>Intakes were estimated with food-frequency questionnaire in 1990 except for iron supplement use from the 1992 questionnaire.</p>5<p>Nutrient values were energy-adjusted intake.</p>6<p>The serum ferritin levels were measured in a random sample of 305 men in HPFS.</p

Characteristics of colorectal cancer controls by levels of leukocyte genomic DNA methylation in a case-control study nested within the Nurses’ Health Study.

a<p>Regular aspirin use was defined as intake of at least two 325-mg tablets per week in the NHS.</p>b<p>The body mass index is weight in kilograms divided by the square of the height in meters.</p>c<p>MET denotes metabolic equivalent. Met -hours = sum of the average time/wk in each activity x MET value of each activity. One MET, the energy spent sitting quietly, is equal to 3.5 ml of oxygen uptake per kilograms of body weight per minute for a 70-kg adult.</p>d<p>Nutrient values (calcium, folate, and vitamin D) represent the mean of energy-adjusted intakes.</p

Association between leukocyte genomic DNA methylation level and colorectal cancer risk in the nested case-control study.

<p>Multivariate ORs are adjusted for race, height (continuous), pack-years of smoking (continuous), body mass index (continuous), physical activity (in quartiles), family history of colorectal cancer (yes or no), history of colonoscopy or sigmoidoscopy (yes or no), alcohol intake (continuous), intake of red and processed meat (in quartiles), vitamin D intake (continuous), calcium intake (continuous), and aspirin use (non-users vs. ever users).</p

Characteristics of colorectal cancer cases and controls in the nested case-control study within the Nurses’ Health Study.

a<p>Body mass index is weight in kilograms divided by the square of the height in meters.</p>b<p>MET denotes metabolic equivalent. Met –hours = sum of the average time/wk in each activity x MET value of each activity. One MET, the energy spent sitting quietly, is equal to 3.5 ml of oxygen uptake per kilograms of body weight per minute for a 70-kg adult.</p>c<p>Nutrient values (calcium, vitamin D, and folate) represent the mean of energy-adjusted intakes.</p

Flow diagram of the current study.

<p>Based on the availability of adequate follow-up and tumor molecular data among incident colorectal cancers identified in the Nurses' Health Study (NHS; N = 121,701) and the Health Professionals Follow-up Study (HPFS; N = 51,529), a total of 1072 stage I–IV colorectal cancer cases diagnosed up to 2004 were included. MSI, microsatellite instability; MSS, microsatellite stable.</p