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标题：Colorectal Cancer Epidemiology in the Nurses’ Health Study
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作者：Dong Hoon Lee ; NaNa Keum ; Edward L. Giovannucci 等
期刊名称：American journal of public health
印刷版ISSN：0090-0036
出版年度：2016
卷号：106
期号：9
页码：1599-1607
DOI：10.2105/AJPH.2016.303320
语种：English
出版社：American Public Health Association
摘要：Objectives. To review the contribution of the Nurses’ Health Study (NHS) to identifying risk and protective factors for colorectal adenomas and colorectal cancer (CRC). Methods. We performed a narrative review of the publications using the NHS between 1976 and 2016. Results. Existing epidemiological studies using the NHS have reported that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC. Moreover, modifiable factors, such as physical activity, vitamin D, folate, insulin and insulin-like growth factor binding protein-1, and diet quality, were identified to be associated with survival among CRC patients. In recent years, molecular pathological epidemiological studies have been actively conducted and have shown refined results by molecular subtypes of CRC. Conclusions. The NHS has provided new insights into colorectal adenomas, CRC etiology, and pathogenic mechanisms. With its unique strengths, the NHS should continue to contribute to the field of CRC epidemiology and play a major role in public health. Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men worldwide. 1 In 2012, an estimated 1.36 million new cases (women: 614 000; men: 746 000) of CRC were diagnosed, which accounted for 9.7% of total cancers, excluding nonmelanoma skin cancer. 1 The rates vary more than 10 times across the world; high-income countries have approximately 2.5 times higher rates than do low-income countries. Moreover, CRC is the third leading cause of cancer death in women and the fourth in men globally, with the combined number of total deaths reaching 694 000 (8.5% of total cancer deaths). 1 The number of cancer survivors has also grown rapidly over the past several decades. Research on CRC has drawn much attention. Many epidemiological studies, including the Nurses’ Health Study (NHS), have been conducted to provide evidence for CRC prevention and for improving survival among patients with CRC. We have briefly summarized the key findings from the NHS, a pioneering large prospective cohort study ( Tables 1 and and2 2 ). TABLE 1— Summary of Selected Studies: Nurses’ Health Study, 1976–2016 Study Study Cohort (Study Years) Total No. (No. Cases) Exposure Outcome RR (95% CI) Adjustments Fat/Fiber Willett et al. 2 NHS (1980–1986) 88 751 (150) Animal fat CC 1.89 (1.13, 3.15) Age, total energy intake Quintile 5 vs 1 Red meat 2.49 (1.24, 5.03) ≥ 1/d vs < 1/mo Processed meat 1.21 (0.53, 2.72) ≥ 1/d vs < 1/mo Cereal fiber 0.74 (0.43, 1.21) Quintile 5 vs 1 Fruit fiber 0.62 (0.37, 1.05) Quintile 5 vs 1 Vegetable fiber 1.07 (0.65, 1.76) Quintile 5 vs 1 Michels et al. 3 NHS (1984–2000) 76 947 (919) Cereal fiber CRC 0.94 (0.79, 1.11) Age, period, family history of CRC, history of sigmoidoscopy or colonoscopy, height, BMI, PA, aspirin, smoking, multivitamin, total energy intake, alcohol, dietary folate, red meat, processed meat, glycemic load, calcium, methionine, menopausal status, hormone use Quintile 5 vs 1 Fruit fiber 0.87 (0.73, 1.04) Quintile 5 vs 1 Vegetable fiber 1.05 (0.90, 1.23) Quintile 5 vs 1 Bernstein et al. 4 NHS (1980–2010) 87 108 (1735) Processed meat Per 1 serving/d CRC Pooled HR (95% CI) 1.15 (1.01, 1.32) Age, 2-follow-up cycle, family history of CRC, history of endoscopy, smoking, BMI, PA, multivitamin, menopausal status and hormone use, aspirin, total energy intake, alcohol, folate, calcium, vitamin D, fiber HPFS (1986–2010) 47 389 (996) Proximal CC 0.99 (0.79, 1.24) Distal CC 1.36 (1.09, 1.69) Folate Giovannucci et al. 5 NHS (1980–1990) 15 984 (564) Methyl availability CRA 0.66 (0.46, 0.95) Age, family history of CRC, indications for endoscopy, history of endoscopy, total energy intake, saturated fat, fiber, BMI Total folate Quintile 5 vs 1 Alcohol intake 2 drinks/d vs 0 1.84 (1.19, 2.86) High alcohol and low folate vs low alcohol and high folate 2.71 (1.61, 4.58) Giovannucci et al. 6 NHS (1980–1994) 88 756 (442) Total folate > 400 vs < 200 μg/d CC 0.69 (0.52, 0.93) Age, family history of CRC, aspirin, smoking, BMI, PA, red meat, alcohol, methionine, fiber Chen et al. 7 NHS (1989–1994) 970 (257) MTHFR CRA Total CRA Age family history, smoking, BMI, folate, methionine, alcohol, fiber, saturated fat Genotype: val/val vs val/ala or ala/ala 1.35 (0.84, 2.17) Small CRA 1.36 (0.76, 2.45) Large CRA 1.32 (0.66, 2.66) Wu et al. 8 ^, ^a NHS, HPFS (1996–2004) 672 (9134) Folic acid supplementation 1 mg/d vs placebo Recurrent CRA 0.87 (0.65, 1.16) Age, gender, length of trial, time between start of trial and last endoscopy Lee et al. 9 NHS, HPFS (1980–2004) 135 151 (2299) Total folate > 800 vs < 250 μg/d CRC 0.69 (0.51, 0.94) Age, calendar year, smoking, PA, aspirin, height, BMI, family history of CRC, menopausal status and hormone therapy, history of endoscopy, red meat, alcohol, calcium, total energy intake 79 652 (5655) Total folate > 800 vs < 250 μg/d CRA 0.68 (0.60, 0.78) Further adjusting for recent endoscopy year, indications for endoscopy Cho et al. 10 ^, ^b NHS (1989–2010) 1825 (618) Plasma level of unmetabolized folic acid CRC 1.03 (0.73, 1.46) 1.12 (0.81, 1.55) Age, date of blood draw, gender, race, height, fasting status, smoking, BMI, PA, family history of CRC, history of screening, alcohol, red and processed meat, vitamin D, calcium, aspirin HPFS (1993–2010) < 0.5 nmol/L vs 0 ≥ 0.5 nmol/L vs 0 Calcium and vitamin D Kampman et al. 11 NHS (1980–1988) 8935 (350) Total vitamin D CRA 0.68 (0.41, 1.13) Age, total energy intake, BMI, alcohol, folate, saturated fat, fiber, indications for endoscopy, history of endoscopy, family history of colon cancer Quintile 5 vs 1 Martinez et al. 12 NHS (1980–1992) 89 448 (501) Total vitamin D CRC 0.42 (0.19, 0.91) Age, BMI, PA, family history of CRC, aspirin, smoking, red meat, alcohol Quintile 5 vs 1 Wu et al. 13 NHS (1980–1996) 87 998 (626) Total calcium > 1250 vs ≤ 500 mg/d Distal CC Pooled RR (95% CI) 0.65 (0.43, 0.98) Age, family history, BMI, PA, smoking, aspirin, red meat, alcohol, postmenopausal hormone use, menopausal status HPFS (1986–1996) 47 344 (399) Feskanich et al. 14 ^, ^b NHS (1989–2000) 576 (193) Plasma 25(OH)D Quintile 5 vs 1 CRC 0.53 (0.27, 1.04) Age, time of blood draw, BMI, PA, smoking, menopausal status, HRT use, aspirin, family history of CRC, calcium, folate, methionine, retinol, red meat, alcohol Wu et al. 15 ^, ^b NHS (1989–2000) 576 (193) Plasma 25(OH)D Quintile 5 vs 1 CRC Pooled OR (95% CI) 0.66 (0.42, 1.05) Age, time of blood draw, BMI, PA, smoking, aspirin, family history of CRC, calcium, folate, retinol, red and processed meat, alcohol (NHS additionally included menopausal status and postmenopausal hormone use) HPFS (1993–2002) 535 (179) CC 0.54 (0.34, 0.86) Smoking Giovannucci et al. 16 NHS (1976–1990) 12 143 (564) Smoking pack-years accumulated within the past 20 y CRA Small adenoma Age, saturated fat, fiber, folate, alcohol, BMI, family history of CRC, pack-years of cigarettes smoked in the past 1.45 (1.25, 1.68) Large adenoma 1.31 (1.17, 1.47) 118 334 (586) Among women who started smoking > 10 cigarettes/d CRC After 35–39 y follow-up 1.47 (1.07, 2.01) After 40–44 y follow-up 1.63 (1.14, 2.33) After 45 y 2.00 (1.14, 3.49) Kenfield et al. 17 NHS (1980–2004) 104 519 (578) Smoking CRC death Current smoker Age, follow-up period, history of hypertension, diabetes, high cholesterol levels, BMI, change in weight, alcohol, PA, oral contraceptives use, postmenopausal estrogen therapy use and menopausal status, parental history of disease, age at starting smoking, red and processed meat, calcium, folate, aspirin Current vs never smoker 1.63 (1.29, 2.05) Former vs never smoker Former smoker 1.23 (1.02, 1.49) Energy balance Giovannucci et al. 18 NHS (1986–1992) 13 057 (439) Total PA (MET-h/wk) Quintile 5 vs 1 CRA 0.58 (0.40, 0.86) Age, family history of CRC, history of endoscopy, smoking, aspirin, animal fat, fiber, alcohol, folate, methionine WC, WHR 1 quintile increment WC 1.55 (1.09, 2.21) WHR 1.55 (1.08, 2.21) Wei et al. 19 ^, ^b NHS (1989–2000) 532 (182) C-peptide CC 1.76 (0.85, 3.63) Age, date of blood draw, fasting status, BMI, PA, smoking, alcohol, family history of CRC, aspirin, history of screening, menopausal status, postmenopausal hormones Quartile 4 vs 1 IGFBP-1 0.28 (0.11, 0.75) Quartile 4 vs 1 IGF-1/IGFBP-3 2.82 (1.35, 5.88) Quartile 4 vs 1 Wei et al. 20 ^, ^b NHS (1989–1998) 760 (380) C-peptide Quartile 4 vs 1 CRA 1.63 (1.01, 2.66) Age, period of and indications for endoscopy, date of blood draw, BMI, PA, smoking, alcohol, family history of CRC, aspirin, menopausal status, HRT use Survival Meyerhartdt et al. 21 NHS (1986–2004) 573 (72) Postdiagnosis PA ≥ 18 vs < 3 MET h/wk CRC death 0.39 (0.18, 0.82) Age, BMI, stage of disease, grade of tumor differentiation, location of primary tumor, year of diagnosis, chemotherapy, time from diagnosis to PA measurement, change in BMI before and after diagnosis, smoking 573 (121) Overall death 0.43 (0.25, 0.74) Ng et al. 22 ^, ^b NHS (1989–2005) 304 (96) Plasma 25(OH)D Quartile 4 vs 1 CRC death Overall death Pooled HR (95% CI) 0.61 (0.31, 1.19) 0.52 (0.29, 0.94) Age, season of blood draw, gender, stage of disease, grade of tumor differentiation, location of primary tumor, year of diagnosis, BMI at diagnosis, postdiagnosis PA HPFS (1993–2005) 304 (123) Wolpin et al. 23 ^, ^b NHS (1989–2005) 301 (95) Plasma folate Quintile 5 vs 1 CRC death Overall death Pooled HR 0.42 (0.20, 0.88) 0.46 (0.24, 0.88) Age, stage of disease, histologic differentiation, chemotherapy, tumor location, period of diagnosis, BMI, PA, smoking, aspirin, alcohol, total vitamin D, postmenopausal hormone use HPFS (1993–2005) 301 (122) Wolpin et al. 24 ^, ^b NHS (1989–2004) 373 (108) C-peptide Quartile 4 vs 1 IGFBP-1 Quartile 4 vs 1 Overall death 2.11 (1.06, 4.21) Age, gender, stage of disease, histologic differentiation, tumor location, period of diagnosis, time between last meal and plasma collection, chemotherapy, smoking, aspirin, alcohol, total vitamin D, postmenopausal hormone HPFS (1993–2004) 0.44 (0.24, 0.81) Fung et al. 25 NHS (1986–2010) 1201 (162) AHEI-2010 CRC death 0.72 (0.43, 1.21) Age, PA, BMI, weight change, stage of disease, chemotherapy, smoking, total energy intake, colon or rectal cancer, stage of disease, date of CRC diagnosis Quintile 5 vs 1 1201 (435) Overall death 0.71 (0.52, 0.98) Molecular pathogenic epidemiology Liao et al. 26 NHS (1980–2011) 964 (190) Aspirin Postdiagnosis regular use vs no use CRC death Overall death Pooled HR (95% CI) PIK3CA mutation 0.18 (0.06, 0.61) 0.54 (0.31, 0.94) Age, gender, stage of disease, BMI, year of diagnosis, time from diagnosis to first measurement of aspirin use after diagnosis, regular use or nonuse of aspirin before diagnosis, tumor location, tumor differentiation, microsatellite instability status, CIMP, KRAS mutation, BRAF mutation, LINE-1 methylation, and the presence or absence of PTGS2 expression HPFS (1986–2011) 964 (395) Wild-type PIK3CA 0.96 (0.69, 1.32) 0.94 (0.75, 1.17) Nishihara et al. 27 NHS (1980–2008) 134 204 (714) Smoking duration of cessation (10–19, 20–39, ≥ 40 y) vs current smoker CRC CIMP-high CRC 0.53 (0.29, 0.95) 0.52 (0.32, 0.85) 0.50 (0.27, 0.94) Age, gender, BMI, family history of CRC, aspirin, PA, alcohol, total energy intake, red meat HPFS (1986–2008) CIMP-low CRC 1.07 (0.81, 1.42) 0.98 (0.77, 1.26) 0.95 (0.69, 1.32) Open in a separate window Note . 25(OH)D = 25-hydroxyvitamin D; AHEI-2010 = alternative healthy eating index-2010; BMI = body mass index; CC = colon cancer; CI = confidence interval; CRA = colorectal adenoma; CIMP = CpG island methylator phenotype; CRC = colorectal cancer; HPFS = health professional follow-up study; HR = hazard ratio; HRT = hormone replacement therapy; IGF = insulin-like growth factor; IGFBP = insulin-like growth factor binding protein; LINE-1 = long interspersed nuclear element 1; MET = metabolic equivalent task; MTHFR = methylenetetrahydrofolate reductase; NHS = Nurses’ Health Study; OR = odds ratio; PA = physical activity; RR = rate ratio; WC = waist circumference; WHR = waist to hip ratio. ^aRandomized controlled trial. ^bNested case–control study. TABLE 2— Initial Findings on Factors Related to Colorectal Cancer Risk and Survival: Nurses’ Health Study, 1976–2016 Publication Year Factors Association CRC risk 1990 Red meat Positive 1990 Fiber Null 1993 Folate Inverse 1993 Alcohol Positive 1994 Calcium and vitamin D Inverse 1994 Smoking Positive 1995 Aspirin Inverse 1996 Physical activity Inverse 1996 BMI Positive Waist circumference Positive 2013 Smoking cessation Inverse (CIMP-high CRC) Null (CIMP-low CRC) Mortality in CRC patients 2006 Physical activity Inverse 2008 Vitamin D Inverse 2008 Folate Inverse 2009 Insulin Positive IGFBP-1 Inverse 2012 Aspirin Inverse ( PIK3CA mutation) Null (wild type) 2014 Diet quality Inverse Open in a separate window Note . BMI = body mass index; CIMP = CpG island methylator phenotype; CRC = colorectal cancer; IGFBP-1 = insulin-like growth factor binding protein-1.