Prevention of Colorectal Neoplasia

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. There are well-established screening protocols involving fecal testing, radiographic, and endoscopic evaluations that have led to decreased incidence and mortality of CRC in the United States. In addition to screening for CRC, there is interest in preventing colorectal neoplasia by targeting the signaling pathways that have been identified in the pathway of dysplasia progressing to carcinoma. This review will detail the efficacy of multiple potential preventative strategies including lifestyle changes (physical activity, alcohol use, smoking cessation, and obesity); dietary factors (dietary patterns, calcium, vitamin D, fiber, folate, and antioxidants and micronutrients); and chemopreventive agents (nonsteroidal anti-inflammatory drugs, statins, metformin, bisphosphonates, and postmenopausal hormonal therapy).

Keywords

chemoprevention - primary prevention - colorectal cancer - adenoma

• References

• 1 Kohler BA, Sherman RL, Howlader N , et al. Annual report to the Nation on the Status of Cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst 2015; 107 (6) djv048
• 2 Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60 (5) 277-300
• 3 Winawer SJ, Zauber AG, Ho MN , et al; The National Polyp Study Workgroup. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329 (27) 1977-1981
• 4 Mandel JS, Bond JH, Church TR , et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328 (19) 1365-1371
• 5 Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348 (9040) 1467-1471
• 6 King H, Locke FB. Cancer mortality among Chinese in the United States. J Natl Cancer Inst 1980; 65 (5) 1141-1148
• 7 Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer 1971; 28 (1) 3-13
• 8 Trowell H, Southgate DA, Wolever TM, Leeds AR, Gassull MA, Jenkins DJ. Letter: Dietary fibre redefined. Lancet 1976; 1 (7966) 967
• 9 Theisen C. Chemoprevention: what's in a name?. J Natl Cancer Inst 2001; 93 (10) 743
• 10 Kinzler KW, Vogelstein B. Colorectal tumors. In: Vogelstein B, Kinzler KW, , eds. The Genetic Basis of Human Cancer. 2nd ed. New York, NY: McGraw-Hill; 1998: 565-587
• 11 Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61 (5) 759-767
• 12 Kiningham RB. Physical activity and the primary prevention of cancer. Prim Care 1998; 25 (2) 515-536
• 13 Winawer SJ, St John DJ, Bond JH , et al; WHO Collaborating Center for the Prevention of Colorectal Cancer. Prevention of colorectal cancer: guidelines based on new data. Bull World Health Organ 1995; 73 (1) 7-10
• 14 Trojian TH, Mody K, Chain P. Exercise and colon cancer: primary and secondary prevention. Curr Sports Med Rep 2007; 6 (2) 120-124
• 15 Kruk J, Aboul-Enein HY. Physical activity in the prevention of cancer. Asian Pac J Cancer Prev 2006; 7 (1) 11-21
• 16 Wolin KY, Yan Y, Colditz GA, Lee IM. Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer 2009; 100 (4) 611-616
• 17 Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J Natl Cancer Inst 2012; 104 (20) 1548-1561
• 18 Wolin KY, Lee IM, Colditz GA, Glynn RJ, Fuchs C, Giovannucci E. Leisure-time physical activity patterns and risk of colon cancer in women. Int J Cancer 2007; 121 (12) 2776-2781
• 19 Chao A, Connell CJ, Jacobs EJ , et al. Amount, type, and timing of recreational physical activity in relation to colon and rectal cancer in older adults: the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 2004; 13 (12) 2187-2195
• 20 Oguma Y, Shinoda-Tagawa T. Physical activity decreases cardiovascular disease risk in women: review and meta-analysis. Am J Prev Med 2004; 26 (5) 407-418
• 21 Fedirko V, Tramacere I, Bagnardi V , et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol 2011; 22 (9) 1958-1972
• 22 Cho E, Smith-Warner SA, Ritz J , et al. Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann Intern Med 2004; 140 (8) 603-613
• 23 Boffetta P, Hashibe M, La Vecchia C, Zatonski W, Rehm J. The burden of cancer attributable to alcohol drinking. Int J Cancer 2006; 119 (4) 884-887
• 24 Ferrari P, Jenab M, Norat T , et al. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer 2007; 121 (9) 2065-2072
• 25 Seitz HK, Pöschl G, Simanowski UA. Alcohol and cancer. Recent Dev Alcohol 1998; 14: 67-95
• 26 Mizoue T, Inoue M, Wakai K , et al; Research Group for Development and Evaluation of Cancer Prevention Strategies in Japan. Alcohol drinking and colorectal cancer in Japanese: a pooled analysis of results from five cohort studies. Am J Epidemiol 2008; 167 (12) 1397-1406
• 27 Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P. Smoking and colorectal cancer: a meta-analysis. JAMA 2008; 300 (23) 2765-2778
• 28 Botteri E, Iodice S, Raimondi S, Maisonneuve P, Lowenfels AB. Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology 2008; 134 (2) 388-395
• 29 Giovannucci E. An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2001; 10 (7) 725-731
• 30 Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 2003; 3 (10) 733-744
• 31 Karahalios A, English DR, Simpson JA. Weight change and risk of colorectal cancer: a systematic review and meta-analysis. Am J Epidemiol 2015; 181 (11) 832-845
• 32 Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 2007; 16 (12) 2533-2547
• 33 Larsson SC, Wolk A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr 2007; 86 (3) 556-565
• 34 Qasim A, O'Morain C. Primary prevention of colorectal cancer: are we closer to reality?. Eur J Gastroenterol Hepatol 2010; 22 (1) 9-17
• 35 Koushik A, Hunter DJ, Spiegelman D , et al. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. J Natl Cancer Inst 2007; 99 (19) 1471-1483
• 36 van't Veer P, Jansen MC, Klerk M, Kok FJ. Fruits and vegetables in the prevention of cancer and cardiovascular disease. Public Health Nutr 2000; 3 (1) 103-107
• 37 Michels KB, Edward Giovannucci, Joshipura KJ , et al. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst 2000; 92 (21) 1740-1752
• 38 Lee JE, Chan AT. Fruit, vegetables, and folate: cultivating the evidence for cancer prevention. Gastroenterology 2011; 141 (1) 16-20
• 39 van Duijnhoven FJ, Bueno-De-Mesquita HB, Ferrari P , et al. Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2009; 89 (5) 1441-1452
• 40 van Breda SG, de Kok TM, van Delft JH. Mechanisms of colorectal and lung cancer prevention by vegetables: a genomic approach. J Nutr Biochem 2008; 19 (3) 139-157
• 41 Aune D, Lau R, Chan DS , et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology 2011; 141 (1) 106-118
• 42 Crosara Teixeira M, Braghiroli MI, Sabbaga J, Hoff PM. Primary prevention of colorectal cancer: myth or reality?. World J Gastroenterol 2014; 20 (41) 15060-15069
• 43 Orlich MJ, Singh PN, Sabaté J , et al. Vegetarian dietary patterns and the risk of colorectal cancers. JAMA Intern Med 2015; 175 (5) 767-776
• 44 Yoon H, Benamouzig R, Little J, François-Collange M, Tomé D. Systematic review of epidemiological studies on meat, dairy products and egg consumption and risk of colorectal adenomas. Eur J Cancer Prev 2000; 9 (3) 151-164
• 45 Chao A, Thun MJ, Connell CJ , et al. Meat consumption and risk of colorectal cancer. JAMA 2005; 293 (2) 172-182
• 46 Cross AJ, Ferrucci LM, Risch A , et al. A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res 2010; 70 (6) 2406-2414
• 47 MacLennan R, Macrae F, Bain C , et al; Australian Polyp Prevention Project. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. J Natl Cancer Inst 1995; 87 (23) 1760-1766
• 48 Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 1990; 323 (24) 1664-1672
• 49 Chan DS, Lau R, Aune D , et al. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS ONE 2011; 6 (6) e20456
• 50 Figueiredo JC, Hsu L, Hutter CM , et al; CCFR; GECCO. Genome-wide diet-gene interaction analyses for risk of colorectal cancer. PLoS Genet 2014; 10 (4) e1004228
• 51 Beresford SA, Johnson KC, Ritenbaugh C , et al. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006; 295 (6) 643-654
• 52 Prentice RL, Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control 1990; 1 (1) 81-97 , discussion 99–109
• 53 Weijenberg MP, Lüchtenborg M, de Goeij AF , et al. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes. Cancer Causes Control 2007; 18 (8) 865-879
• 54 Kuriki K, Wakai K, Hirose K , et al. Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as biomarkers for dietary intakes of fish, fat, and fatty acids. Cancer Epidemiol Biomarkers Prev 2006; 15 (10) 1791-1798
• 55 Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2008; (1) CD003548
• 56 Wactawski-Wende J, Kotchen JM, Anderson GL , et al; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006; 354 (7) 684-696
• 57 Keum N, Aune D, Greenwood DC, Ju W, Giovannucci EL. Calcium intake and colorectal cancer risk: dose-response meta-analysis of prospective observational studies. Int J Cancer 2014; 135 (8) 1940-1948
• 58 Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J ; European Cancer Prevention Organisation Study Group. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet 2000; 356 (9238) 1300-1306
• 59 Baron JA, Beach M, Mandel JS , et al; Calcium Polyp Prevention Study Group. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999; 340 (2) 101-107
• 60 Bond JH ; Practice Parameters Committee of the American College of Gastroenterology. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Am J Gastroenterol 2000; 95 (11) 3053-3063
• 61 Lee JE, Li H, Chan AT , et al. Circulating levels of vitamin D and colon and rectal cancer: the Physicians' Health Study and a meta-analysis of prospective studies. Cancer Prev Res (Phila) 2011; 4 (5) 735-743
• 62 Weinstein SJ, Yu K, Horst RL, Ashby J, Virtamo J, Albanes D. Serum 25-hydroxyvitamin D and risks of colon and rectal cancer in Finnish men. Am J Epidemiol 2011; 173 (5) 499-508
• 63 Jacobs ET, Alberts DS, Benuzillo J, Hollis BW, Thompson PA, Martínez ME. Serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma recurrence. J Steroid Biochem Mol Biol 2007; 103 (3–5) 752-756
• 64 Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2011; 155 (12) 827-838
• 65 Ingraham BA, Bragdon B, Nohe A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin 2008; 24 (1) 139-149
• 66 Moore MA, Park CB, Tsuda H. Soluble and insoluble fiber influences on cancer development. Crit Rev Oncol Hematol 1998; 27 (3) 229-242
• 67 Asano T, McLeod RS. Dietary fibre for the prevention of colorectal adenomas and carcinomas. Cochrane Database Syst Rev 2002; 2 (2) CD003430
• 68 Alberts DS, Martínez ME, Roe DJ , et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med 2000; 342 (16) 1156-1162
• 69 Fuchs CS, Giovannucci EL, Colditz GA , et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 1999; 340 (3) 169-176
• 70 Michels KB, Fuchs CS, Giovannucci E , et al. Fiber intake and incidence of colorectal cancer among 76,947 women and 47,279 men. Cancer Epidemiol Biomarkers Prev 2005; 14 (4) 842-849
• 71 Giovannucci E, Stampfer MJ, Colditz GA , et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 1993; 85 (11) 875-884
• 72 Duthie SJ. Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 1999; 55 (3) 578-592
• 73 Carroll C, Cooper K, Papaioannou D , et al. Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer. Aliment Pharmacol Ther 2010; 31 (7) 708-718
• 74 Cole BF, Baron JA, Sandler RS , et al; Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007; 297 (21) 2351-2359
• 75 Chan AT, Giovannucci EL. Primary prevention of colorectal cancer. Gastroenterology 2010; 138 (6) 2029-2043.e10
• 76 Jänne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med 2000; 342 (26) 1960-1968
• 77 Arber N, Levin B. Chemoprevention of colorectal neoplasia: the potential for personalized medicine. Gastroenterology 2008; 134 (4) 1224-1237
• 78 Garcia-Albeniz X, Chan AT. Aspirin for the prevention of colorectal cancer. Best Pract Res Clin Gastroenterol 2011; 25 (4–5) 461-472
• 79 Fajardo AD, Robb BW. Chemoprevention for colorectal neoplasia. Clin Colon Rectal Surg 2008; 21 (4) 304-312
• 80 Draft Recommendation Statement. Aspirin to Prevent Cardiovascular Disease and Cancer. US Preventive Services Task Force; 2015
• 81 Sandler RS, Halabi S, Baron JA , et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003; 348 (10) 883-890
• 82 Rostom A, Dubé C, Lewin G , et al; U.S. Preventive Services Task Force. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007; 146 (5) 376-389
• 83 Grau MV, Sandler RS, McKeown-Eyssen G , et al. Nonsteroidal anti-inflammatory drug use after 3 years of aspirin use and colorectal adenoma risk: observational follow-up of a randomized study. J Natl Cancer Inst 2009; 101 (4) 267-276
• 84 Flossmann E, Rothwell PM ; British Doctors Aspirin Trial and the UK-TIA Aspirin Trial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007; 369 (9573) 1603-1613
• 85 Cook NR, Lee IM, Gaziano JM , et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294 (1) 47-55
• 86 Cole BF, Logan RF, Halabi S , et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 2009; 101 (4) 256-266
• 87 Burn J, Gerdes AM, Macrae F , et al; CAPP2 Investigators. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011; 378 (9809) 2081-2087
• 88 Benamouzig R, Uzzan B, Deyra J , et al; Association pour la Prévention par l'Aspirine du Cancer Colorectal Study Group (APACC). Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial. [Erratum appears in Gut. 2012 Mar;61(3):472] Gut 2012; 61 (2) 255-261
• 89 Baron JA, Cole BF, Sandler RS , et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003; 348 (10) 891-899
• 90 Dubé C, Rostom A, Lewin G , et al; U.S. Preventive Services Task Force. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007; 146 (5) 365-375
• 91 Whitlock EP, Williams SB, Burda BU, Freightner A, Beil T. Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms: A Systematic Evidence Review for the U.S. Preventive Services Task Force. AHRQ Publication; 2015: 13
• 92 Nan H, Hutter CM, Lin Y , et al; CCFR; GECCO. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA 2015; 313 (11) 1133-1142
• 93 Bertagnolli MM, Eagle CJ, Zauber AG , et al; APC Study Investigators. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006; 355 (9) 873-884
• 94 Kerr DJ, Dunn JA, Langman MJ , et al; VICTOR Trial Group. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 2007; 357 (4) 360-369
• 95 Chan AT, Sima CS, Zauber AG, Ridker PM, Hawk ET, Bertagnolli MM. C-reactive protein and risk of colorectal adenoma according to celecoxib treatment. Cancer Prev Res (Phila) 2011; 4 (8) 1172-1180
• 96 Solomon SD, Wittes J, Finn PV , et al; Cross Trial Safety Assessment Group. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008; 117 (16) 2104-2113
• 97 Meyskens Jr FL, McLaren CE, Pelot D , et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila) 2008; 1 (1) 32-38
• 98 Zell JA, Pelot D, Chen WP, McLaren CE, Gerner EW, Meyskens FL. Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila) 2009; 2 (3) 209-212
• 99 Laukaitis CM, Gerner EW. DFMO: targeted risk reduction therapy for colorectal neoplasia. Best Pract Res Clin Gastroenterol 2011; 25 (4–5) 495-506
• 100 Lytras T, Nikolopoulos G, Bonovas S. Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies. World J Gastroenterol 2014; 20 (7) 1858-1870
• 101 Bonovas S, Filioussi K, Flordellis CS, Sitaras NM. Statins and the risk of colorectal cancer: a meta-analysis of 18 studies involving more than 1.5 million patients. J Clin Oncol 2007; 25 (23) 3462-3468
• 102 Broughton T, Sington J, Beales IL. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterol 2012; 12: 36
• 103 Xiao H, Yang CS. Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int J Cancer 2008; 123 (5) 983-990
• 104 Sehdev A, Shih YC, Vekhter B, Bissonnette MB, Olopade OI, Polite BN. Metformin for primary colorectal cancer prevention in patients with diabetes: a case-control study in a US population. Cancer 2015; 121 (7) 1071-1078
• 105 Tsilidis KK, Capothanassi D, Allen NE , et al. Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial. Diabetes Care 2014; 37 (9) 2522-2532
• 106 Marks AR, Pietrofesa RA, Jensen CD, Zebrowski A, Corley DA, Doubeni CA. Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus. Cancer Epidemiol Biomarkers Prev 2015; 24 (11) 1692-1698
• 107 Kowall B, Stang A, Rathmann W, Kostev K. No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: database analyses from Germany and the UK. Pharmacoepidemiol Drug Saf 2015; 24 (8) 865-874
• 108 Zhang ZJ, Zheng ZJ, Kan H , et al. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care 2011; 34 (10) 2323-2328
• 109 Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS ONE 2013; 8 (8) e71583
• 110 Thosani N, Thosani SN, Kumar S , et al. Reduced risk of colorectal cancer with use of oral bisphosphonates: a systematic review and meta-analysis. J Clin Oncol 2013; 31 (5) 623-630
• 111 Singh H, Nugent Z, Demers A, Mahmud S, Bernstein C. Exposure to bisphosphonates and risk of colorectal cancer: a population-based nested case-control study. Cancer 2012; 118 (5) 1236-1243
• 112 Khalili H, Huang ES, Ogino S, Fuchs CS, Chan AT. A prospective study of bisphosphonate use and risk of colorectal cancer. J Clin Oncol 2012; 30 (26) 3229-3233
• 113 Rennert G, Pinchev M, Rennert HS, Gruber SB. Use of bisphosphonates and reduced risk of colorectal cancer. J Clin Oncol 2011; 29 (9) 1146-1150
• 114 Grodstein F, Martinez ME, Platz EA , et al. Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med 1998; 128 (9) 705-712
• 115 U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med 2002; 137 (10) 834-839
• 116 Chlebowski RT, Wactawski-Wende J, Ritenbaugh C , et al; Women's Health Initiative Investigators. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 2004; 350 (10) 991-1004
• 117 Solimando R, Bazzoli F, Ricciardiello L. Chemoprevention of colorectal cancer: a role for ursodeoxycholic acid, folate and hormone replacement treatment?. Best Pract Res Clin Gastroenterol 2011; 25 (4–5) 555-568
• 118 Simon MS, Chlebowski RT, Wactawski-Wende J , et al. Estrogen plus progestin and colorectal cancer incidence and mortality. J Clin Oncol 2012; 30 (32) 3983-3990