Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer

Seminars in Cancer Biology

Volumn 52, Issue , 2018, Pages 1-8

  Rajpoot, Meenakshi ^a   Sharma, Anil K ^a   Sharma, Anil ^b   Gupta, Girish Kumar ^a  

^a MAHARISHI MARKANDESHWAR DEEMED TO BE UNIVERSITY   (India)

^b MAYO GRADUATE SCHOOL   (United States)

Author keywords

Biomarker; Cancer; Flora; Microbiome; Personalized medicine

Indexed keywords

PREBIOTIC AGENT; PROBIOTIC AGENT; SYNBIOTIC AGENT; TUMOR MARKER;

BIOINFORMATICS; CANCER GROWTH; CANCER PREVENTION; CANCER SCREENING; CANCER THERAPY; DISEASE COURSE; DYSBIOSIS; FECAL MICROBIOTA TRANSPLANTATION; GENE OVEREXPRESSION; GENE SEQUENCE; HUMAN; INTESTINE FLORA; METAGENOMICS; MICROBIAL COMMUNITY; MICROBIAL DIVERSITY; MICROBIOME; MICROFLORA; MOUTH FLORA; NEXT GENERATION SEQUENCING; NONHUMAN; PERSONALIZED MEDICINE; REVIEW; DNA SEQUENCE; GENETIC VARIATION; GENETICS; MICROBIOLOGY; NEOPLASM; PROCEDURES; TRENDS;

BIOMARKERS, TUMOR; GENETIC VARIATION; HUMANS; METAGENOMICS; MICROBIOTA; NEOPLASMS; PRECISION MEDICINE; SEQUENCE ANALYSIS, DNA;

EID: 85042169186     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2018.02.003     Document Type: Review

References (116)

1. Mulle, J.G., Sharp, W.G., Cubells, J.F., The gut microbiome: a new frontier in autism research. Curr. Psychiatry Rep., 5(2), 2014, 337, 10.1007/s11920-012-0337-0.
2. Fierer, N., Lauber, C.L., Zhou, N., McDonald, D., Costello, E.K., Knight, R., Forensic identification using skin bacterial communities. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 6477–6481.
3. Ursell, L.K., Metcalf, J.L., Parfrey, W., Knight, R., Defining the human microbiome. Nutr. Rev. 70 (2012), S38–S44.
4. Clemente, J.C., Ursell, L.K., Parfrey, L.W., Knight, R., The impact of the gut microbiota on human health: an integrative view. Cell 148 (2012), 1258–1270.
5. Cénit, M.C., Matzaraki, V., Tigchelaar, E.F., et al. Rapidly expanding knowledge on the role of the gut microbiome in health and disease. Biochim. Biophys. Acta 1842:10 (2014), 1981–1992.
6. Wang, Y., Kasper, L.H., The role of microbiome in central nervous system disorders. Brain Behav. Immun. 38 (2014), 1–12.
7. Gill, S.R., Pop, M., DeBoy, R.T., et al. Metagenomic analysis of the human distal gut microbiome. Science 312:5778 (2006), 1355–1359.
8. Turnbaugh, P.J., Ley, R.E., Hamady, M., Fraser-Liggett, C., et al. The human microbiome project: exploring the microbial part of ourselves in a changing world. Nature 449:October (7164) (2007), 804–810.
9. Schwabe, R.F., Jobin, C., The microbiome and cancer. Nat. Rev. Cancer 13:11 (2013), 800–812.
10. Ling, Z., Kong, J., Liu, F., et al. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genom., 11, 2010, 488, 10.1186/1471-2164-11-488.
11. Rajendhran, J., Gunasekaran, P., Human microbiomics. Indian J. Microbiol. 50:1 (2010), 109–112.
12. Sonnenburg, J.L., Fischbach, M.A., Community health care: therapeutic opportunities in the human microbiome. Sci. Transl. Med. 3 (2011), 1–5.
13. Badger, J.H., Ng, P.C., Venter, J.C., The human genome, microbiomes, and disease. Nelson, K.E., (eds.) Metagenomics of the Human Body, 2011, Springer Science+Business Media, New York, 1–14.
14. Khajuria, N., Metgud, R., Role of bacteria in oral carcinogenesis. Indian J. Dent. 6:1 (2015), 37–43.
15. Shreiner, A.B., Kao, J.Y., Young, V.B., The gut microbiome in health and in disease. Curr. Opin. Gastroenterol. 31:1 (2015), 69–75, 10.1097/MOG.0000000000000139.
16. Kelly, B.J., Imai, I., Bittinger, K., et al. Composition and dynamics of the respiratory tract microbiome in intubated patients. Microbiome, 4, 2016, 7, 10.1186/s40168-016-0151-8.
17. Sekirov, I., Russell, S.L., Antunes, L.C., Finlay, B.B., Gut microbiota in health and disease. Physiol. Rev. 90:3 (2010), 859–904, 10.1152/physrev.00045.2009.
18. Qin, J., Li, R., Raes, J., Arumugam, M., et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 (2010), 59–65.
19. The Human Microbiome Project Consortium, Structure, function and diversity of the healthy human microbiome. Nature 486 (2012), 207–214.
20. Fraher, M., O'Toole, P., Quigley, E., Techniques used to characterize the gut microbiota: a guide for the clinician. Nat. Rev. Gastroenterol. Hepatol. 9 (2012), 312–322.
21. Kau, A., Ahern, P., Griffin, N., Goodman, A., Gordon, J., Human nutrition, the gut microbiome and the immune system. Nature 474 (2011), 327–336.
22. Tyler, A.D., Smith, M.I., Silverberg, M.S., Analyzing the human microbiome: a how to guide for physicians. Am. J. Gastroenterol. 109 (2014), 983–993, 10.1038/ajg.2014.73.
23. Russo, E., Taddei, A., Ringressi, M.N., et al. The interplay between the microbime and the adaptive immune response in cancer development. Therap. Adv. Gastroenterol. 9:4 (2016), 594–605.
24. Morgan, X.C., Huttenhower, C., Chapter 12: human microbiome analysis. PLoS Comput. Biol., 8(12), 2012, e1002808, 10.1371/journal.pcbi.1002808.
25. Karin, M., Jobin, C., Balkwill, F., Chemotherapy, immunity and microbiota—a new triumvirate?. NatMed 20:2 (2014), 126–127.
26. Costello, E.K., Lauber, C.L., Hamady, M., Bacterial community variation in human body habitats across space and time. Science 326 (2009), 1694–1697, 10.1126/science.1177486.
27. Fredricks, D.N., Fiedler, T.L., Marrazzo, J.M., Molecular identification of bacteria associated with bacterial vaginosis. N. Engl. J. Med. 353:18 (2005), 1899–1911.
28. Lloyd-Price, J., Abu-Ali, G., Huttenhower, C., The healthy human microbiome. Genome Med., 8, 2016, 51.
29. Peterson, J., Garges, S., Giovanni, M., et al. The NIH human microbiome project. Genome Res. 19:12 (2009), 2317–2323, 10.1101/gr.096651.109.
30. Zaura, E., Keijser, B.J.F., Huse, S.M., et al. Defining the healthy core microbiome of oral microbial communities. BMC Microbiol., 9, 2009, 259, 10.1186/1471-2180-9-259.
31. Dethlefsen, L., McFall-Ngai, M., Relman, D.A., An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449 (2007), 811–818.
32. Zarco, M.F., Vess, T.J., Ginsburg, G.S., The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis. 18:2 (2012), 109–120.
33. Nasidze, I., Li, J., Quinque, D., Tang, K., Stoneking, M., Global diversity in the human salivary microbiome. Genome Res. 19 (2009), 636–643.
34. Ravel, J., Gajer, P., Abdo, Z., et al. Vaginal micromicrobiome of reproductive-age women. Proc. Natl. Acad. Sci. U. S. A. 108:Suppl. 1 (2011), 4680–4687.
35. Grice, E.A., Kong, H.H., Conlan, S., et al. Topographical and temporal diversity of the human skin microbiome. Science 324 (2009), 1190–1192.
36. Robinson, C.J., Bohannan, B.J., Young, V.B., From structure to function: the ecology of host-associated microbial communities. Microbiol. Mol. Biol. Rev. 74 (2010), 453–476.
37. Wade, W.G., The oral microbiome in health and disease. Pharmacol. Res. 69 (2013), 137–143.
38. Gerritsen, J., Smidt, H., Rijkers, G.T., de Vos, W.M., Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr. 6:3 (2011), 209–240, 10.1007/s12263-011-0229-7.
39. Gorbach, S.L., Chapter 95 microbiology of the gastrointestinal tract. Baron, S., (eds.) Medical Microbiology, 4th edition, 1996, University of Texas Medical Branch at Galveston, Galveston (TX).
40. Perez-Chanona, E., Trinchieri, G., The role of microbiota in cancer therapy. Curr. Opin. Immunol. 39 (2016), 75–81, 10.1016/j.coi.2016.01.003.
41. Castellarin, M., Warren, R.L., Freeman, J.D., et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22:2 (2012), 299–306.
42. Tahara, T., Yamamoto, E., Suzuki, H., et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 74:5 (2014), 1311–1318, 10.1158/0008-5472.
43. Aas, J.A., Paster, B.J., Stokes, B.J., et al. Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol., 2005, 5721–5732.
44. Dewhirst, F.E., Chen, T., Izard, J., Paster, B.J., Tanner, A.C., Yu, W.H., Lakshmanan, A., Wade, W.G., The human oral microbiome. J. Bacteriol. 192:19 (2010), 5002–5017.
45. Avila, M., Ojcius, D.M., Yilmaz, O., The oral microbiota: living with a permanent guest. DNA Cell Biol. 28:8 (2009), 405–411.
46. Kumar, M., Umashankar, D.N., Viswanath, D., Girish, G., Role of the oral microflora in health and disease. J. Indian Acad. Oral Med. Radiol. 25:3 (2013), 184–187.
47. Kilian, M., Chapple, I.L.C., Hannig, M., The oral microbiome—an update for oral healthcare professionals. Br. Dent. J. 221 (2016), 657–666.
48. Xu, X., He, J., Xue, J., et al. Oral cavity contains distinct niches with dynamic microbial communities. Environ. Microbiol. 17 (2015), 699–710.
49. Van't Hof, W., Veerman, E.C., Nieuw Amerongen, A.V., Ligtenberg, A.J., Antimicrobial defense systems in saliva. Monogr. Oral Sci. 24 (2014), 40–51.
50. Jenkinson, H.F., Lamont, R.J., Oral microbial communities in sickness and in health. Trends Microbiol. 13:12 (2005), 589–595.
51. Parahitiyawa, N.B., Scully, C., Leung, W.K., et al. Exploring the oral bacterial flora: current status and future directions. Oral Dis., 16, 2010, 10.
52. Perez-Chaparro, P.J., Goncalves, C., Figueiredo, L.C., et al. Newly identified pathogen sassociated with periodontitis: asystematicreview. J. Dent. Res 93 (2014), 846–858, 10.1177/0022034514542468.
53. Segata, N., Haake, S.K., Mannon, P., et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. GenomeBiol, 13, 2012, R42, 10.1186/gb-2012-13-6-r42.
54. Belizário, J.E., Napolitano, M., Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front. Microbiol., 6, 2015, 1050, 10.3389/fmicb.2015.01050.
55. Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K., Knight, R., Diversity, stability and resilience of the human gut microbiota. Nature 489 (2012), 220–230.
56. Rajilic-Stojanovic, M., de Vos, W.M., The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev. 38 (2014), 996–1047.
57. De Vos, W.M., De Vos, E.A.J., Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr. Rev. 70 (2012), S45–S56.
58. Backhed, F., Ley, R.E., Sonnenburg, J.L., et al. Host-bacterial mutualism in the human intestine. Science 307:5717 (2005), 1915–1920, 10.1126/science.1104816.
59. Eckburg, P.B., Bik, E.M., Bernstein, C.N., et al. Diversity of the human intestinal microbial flora. Science 308:5728 (2005), 1635–1638.
60. Arumugam, M., Raes, J., Pelletier, E., et al. Enterotypes of the human gut microbiome. Nature 473:7346 (2011), 174–180, 10.1038/nature09944.
61. Zackular, J.P., Bexter, N.D., Chan, G.Y., et al. Manipulation of the Gut Microbiota reveals role in colon tumorigenesis. MBio 4:November (6) (2013), e00692–00713, 10.1128/mBio.00692-13.
62. Schwabe, R.F., Jobin, C., The microbiome and cancer. Nat. Rev. Cancer 13:11 (2013), 800–812.
63. Breitbart, M., Haynes, M., Kelley, S., et al. Viral diversity and dynamics in an infant gut. Res. Microbiol. 159 (2008), 367–373.
64. Koenig, J.E., Spor, A., Scalfone, N., et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl. Acad. Sci. U. S. A. 108:Suppl. 1 (2011), 4578–4585.
65. Benson, A.K., Kelly, S.A., Legge, R., et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 18933–18938.
66. Reyes, A., Haynes, M., Hanson, N., et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466 (2010), 334–338.
67. Spor, A., Koren, O., Ley, R., Unravelling the effects of the environment and host genotype on the gut microbiome. Nat. Rev. Microbiol. 9 (2011), 279–290.
68. Turnbaugh, P.J., Hamady, M., Yatsunenko, T., et al. A core gut microbiome in obese and lean twins. Nature 457 (2009), 480–484.
69. Burke, C., Steinberg, P., Rusch, D., et al. Bacterial community assembly based on functional genes rather than species. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 14288–14293.
70. Shroff, K.E., Meslin, K., Cebra, J.J., Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect. Immun. 63:10 (1995), 3904–3913.
71. Round, J.L., Mazmanian, S.K., The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:5 (2009), 313–323, 10.1038/nri2515.
72. McCarville, J.L., Caminero, A., Verdu, E.F., Novel perspectives on therapeutic modulation of the gut microbiota. Therap. Adv. Gastroenterol. 9:4 (2016), 580–593, 10.1177/1756283X16637819.
73. Nosho, K., Sukawa, Y., Adachi, Y., et al. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J. Gastroenterol. 22:2 (2016), 557–566, 10.3748/wjg.v22.i2.557.
74. Mim, K., Cao, Y., Chan, A.T., et al. Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location. Clin. Transl. Gastroenterol., 7, 2016, e200, 10.1038/ctg.2016.53.
75. Ye, X., Wang, R., Bhattacharya, R., et al. Fusobacterium nucleatum subspecies animalis influences proinflammatory cytokine expression and monocyte activation in human colorectal tumors. Cancer Prev. Res. (Phila) 10:7 (2017), 398–409, 10.1158/1940-6207.CAPR-16-0178.
76. Yang, Y., Weng, W., Peng, J., et al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology 152:4 (2017), 851–866, 10.1053/j.gastro.2016.11.018.
77. Kostic, A.D., Gevers, D., Pedamallu, C.S., et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22:2 (2012), 292–298, 10.1101/gr.126573.111.
78. Kostic, A.D., Chun, E., Robertson, L., Glickman, J.N., et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:2 (2013), 207–215, 10.1016/j.chom.2013.07.007.
79. Ito, M., Kanno, S., Nosho, K., et al. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. Int. J. Cancer 137:6 (2015), 1258–1268, 10.1002/ijc.29488.
80. Goulart, M.C., Iano, F.G., Silva, P.M., et al. Manipulation of the human genome: ethics and law. Cienc Saude Coletiva 15:Suppl. 1 (2010), 1709–1713.
81. Vieira, A.T., Fukumori, C., Ferreira, C.M., et al. New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases. Clin. Transl. Immunol., 5(6), 2016.
82. Lahti, L., Salojarvi, J., Salonen, A., et al. Tipping elements in the human intestinal ecosystem. Nat. Commun. 8 (2014), 4344–4355.
83. Li, J., Jia, H., Cai, X., Zhong, H., et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32 (2014), 834–841.
84. Sommer, F., Bäckhed, F., The gut microbiota-masters of host development and physiology. Nat. Rev. Microbiol. 11 (2013), 227–238.
85. De Vos, W.M., Microbial biofilms and the human intestinal microbiome. npj Biofilms Microbiomes, 2015, 15005, 10.1038/npjbiofilms.2015.5.
86. Savage, D.C., Microbial ecology of the gastrointestinal tract. Ann. Rev. Microbiol. 31 (1977), 107–133.
87. Hattori, M., Taylor, T.D., The human intestinal microbiome: a new frontier of human biology. DNA Res. 16:1 (2009), 1–12, 10.1093/dnares/dsn033.
88. Blaut, M., Clavel, T., Metabolic diversity of the intestinal microbiota: implications for health and disease. J. Nutr. 137 (2007), 751S–755S.
89. Ley, R.E., Peterson, D.A., Gordon, J.I., Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124 (2006), 837–848.
90. Collins, J., Borojevic, R., Verdu, E.F., Huizinga, J.D., Ratcliffe, E.M., Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol. Motil. 26 (2014), 98–107.
91. Faith, J.J., Ahern, P.P., Ridaura, V.K., Cheng, J., Gordon, J.I., Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci. Transl. Med., 6, 2014, 220ra11.
92. Cotillard, A., Kennedy, S.P., Kong, L.C., Prifti, E., Pons, N., Le Chatelier, E., et al. Dietary intervention impact on gut microbial gene richness. Nature 500 (2013), 585–588.
93. Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500 (2013), 541–546.
94. David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505 (2014), 559–563.
95. Viaud, S., Daillère, R., Boneca, I.G., Lepage, P., Pittet, M.J., Ghiringhelli, F., Trinchieri, G., Goldszmid, R., Zitvogel, L., Harnessing the intestinal microbiome for optimal therapeutic immunomodulation. Cancer Res. 74:16 (2014), 4217–4221, 10.1158/0008-5472.CAN-14-0987.
96. Bultman, S.J., Emerging roles of the microbiome in cancer. Carcinogenesis 35:2 (2014), 249–255, 10.1093/carcin/bgt392.
97. Vogelstein, B., Papadopoulos, N., Velculescu, V.E., et al. Cancer genome landscapes. Science 339:6127 (2013), 1546–1558.
98. O'Hara, A.M., Shanahan, F., The gut flora as a forgotten organ. EMBO Rep. 7 (2006), 688–693.
99. Cho, S.-H., Jeon, J., Kim, S.I., Personalized medicine in breast cancer: a systematic review. J. Breast Cancer 15:3 (2012), 265–272, 10.4048/jbc.2012.15.3.265.
100. Iida, N., Dzutsev, A., Stewart, C.A., et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342 (2013), 967–970.
101. Viaud, S., Saccheri, F., Mignot, G., et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342 (2013), 971–976.
102. Verma, M., Personalized medicine and cancer. J. Pers. Med. 2 (2012), 1–14, 10.3390/jpm2010001.
103. Jackson, S.E., Chester, J.D., Personalised cancer medicine. Int. J. Cancer 137 (2015), 262–266.
104. Karapetis, C.S., Khambata-Ford, S., Jonker, D.J., O'Callaghan, C.J., et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359:17 (2008), 1757–1765, 10.1056/NEJMoa0804385.
105. Stricker, T., Catenacci, D.V., Seiwert, T.Y., Molecular profiling of cancer-the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic. Semin. Oncol. 38:2 (2011), 173–185, 10.1053/j.seminoncol.2011.01.013.
106. J.M.G. Wilson, G. Jungner, Principles and practice of screening for disease. World Health Organization Public Health Papers, 1968, 34.
107. Biswajit, B., Sukanta, C., Shibendu, B., Role of the oral micro flora in human population: a brief review. Int. J. Pharm. Life Sci. 3 (2012), 2220–2227.
108. Dejea, C.M., Wick, E.C., Hechenbleikner, E.M., et al. Microbiota organization is a distinct feature of proximal colorectal cancers. PNAS 111:51 (2014), 18321–18326.
109. Rubinstein, M.R., Wang, X., Liu, W., et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesion. Cell Host Microbe 14:2 (2013), 195–206, 10.1016/j.chom.2013.07.012.
110. Ogino, S., Lochhead, P., Chan, A.T., et al. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease. Mod. Pathol. 26:4 (2013), 465–484, 10.1038/modpathol.2012.214.
111. Ogino, S., Nishihara, R., VanderWeele, T.J., et al. The role of molecular pathological epidemiology in the study of neoplastic and non-neoplastic diseases in the era of precision medicine. Epidemiology 27:4 (2016), 602–611, 10.1097/EDE.000000000 0000471.
112. Nishi, A., Milner, D.A. Jr, Giovannucci, E.A., et al. Integration of molecular pathology, epidemiology, and social science for global precision medicine. Expert Rev. Mol. Diagn. 16:1 (2016), 11–23, 10.1586/14737159.2016.1115346.
113. Ogino, S., Stampfer, M., Lifestyle factors and microsatellite instability in colorectal cancer: the evolving field of molecular pathological epidemiology. J. Natl. Cancer Inst. 102 (2010), 365–367, 10.1093/jnci/djq031.
114. Ogino, S., Chan, A.T., Fuchs, C.S., et al. Molecular pathological epidemiology of colorectal neoplasia:an emerging transdisciplinary and interdisciplinary field. Gut 60 (2011), 397–411, 10.1136/gut.2010.217182.
115. Morikawa, T., Kuchiba, A., Yamauchi, M., et al. Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA 305 (2011), 1685–1694, 10.1001/jama.2011.513.
116. Liao, X., Lochhead, P., Nishihara, R., et al. Aspirin use, tumor PIK3CA mutation status, and colorectal cancer survival. N. Eng1. J. Med. 367 (2012), 1596–1606, 10.1056/NEJMoa1207756.