A primary justification for dedicating substantial amounts of research funding to large-scale cancer genomics projects of both somatic and germline DNA is that the biological insights will lead to new treatment targets and strategies for cancer therapy. While it is too early to judge the success of these projects in terms of clinical breakthroughs, an alternative rationale is that new genomics techniques can be used to reduce the overall burden of cancer by prevention of new cases occurring and also by detecting them earlier. In particular, it is now becoming apparent that studying the genomic profile of tumors can help to identify new carcinogens and may subsequently result in implementing strategies that limit exposure. In parallel, it may be feasible to utilize genomic biomarkers to identify cancers at an earlier and more treatable stage using screening or other early detection approaches based on prediagnostic biospecimens. While the potential for these techniques is large, their successful outcome will depend on international collaboration and planning similar to that of recent sequencing initiatives.
References
[1]
Wetterstrand K. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP). . Accessed 05-Mar-2015.
[2]
Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR, et al. International network of cancer genome projects. Nature. 2010;464(7291):993–8. doi: 10.1038/nature08987. pmid:20393554
[3]
Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr., Kinzler KW. Cancer genome landscapes. Science (New York, NY). 2013;339(6127):1546–58. doi: 10.1126/science.1235122
[4]
Groenendijk FH, Bernards R. Drug resistance to targeted therapies: deja vu all over again. Molecular oncology. 2014;8(6):1067–83. doi: 10.1016/j.molonc.2014.05.004. pmid:24910388
[5]
Kreimer AR, Johansson M, Waterboer T, Kaaks R, Chang-Claude J, Drogen D, et al. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2013;31(21):2708–15. doi: 10.1200/jco.2012.47.2738
[6]
Riley JL. Combination checkpoint blockade—taking melanoma immunotherapy to the next level. N Engl J Med. 2013;369(2):187–9. doi: 10.1056/NEJMe1305484. pmid:23724866
[7]
Bozic I, Nowak MA. Cancer. Unwanted evolution. Science (New York, NY). 2013;342(6161):938–9. doi: 10.1126/science.1247887
[8]
Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306–13. doi: 10.1038/nature10762. pmid:22258609
[9]
Colditz GA, Wolin KY, Gehlert S. Applying what we know to accelerate cancer prevention. Science translational medicine. 2012;4(127):127rv4. doi: 10.1126/scitranslmed.3003218. pmid:22461645
[10]
Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ. 2004;328(7455):1519. pmid:15213107 doi: 10.1136/bmj.38142.554479.ae
[11]
IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol 100, A Review of Human Carcinogens. Lyon, France: International Agency for Research on Cancer; 2011. Accessed 05-Mar-2015.
[12]
Huang LM, Lu CY, Chen DS. Hepatitis B virus infection, its sequelae, and prevention by vaccination. Current opinion in immunology. 2011;23(2):237–43. doi: 10.1016/j.coi.2010.12.013. pmid:21257300
[13]
Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890–907. pmid:17826171 doi: 10.1016/s0140-6736(07)61416-0
[14]
Peto J. Cancer epidemiology in the last century and the next decade. Nature. 2001;411(6835):390–5. pmid:11357148 doi: 10.1038/35077256
[15]
Parkin DM, Boyd L, Walker LC. 16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011;105 Suppl 2:S77–81. doi: 10.1038/bjc.2011.489. pmid:22158327
[16]
Forman D BF, Brewster DH, Gombe Mbalawa C, Kohler B, Pi？eros M, Steliarova-Foucher E, Swaminathan R and Ferlay J. eds (2013) Cancer Incidence in Five Continents, Vol. X (electronic version) Lyon, IARC. last accessed on 05-Mar-2015. (The printed version of this volume: IARC Scientific Publication No. 164, will be available in 2014)
[17]
Pfeifer GP. Environmental exposures and mutational patterns of cancer genomes. Genome medicine. 2010;2(8):54. doi: 10.1186/gm175. pmid:20707934
[18]
Petitjean A ME, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat. 2007;28(6):622–9 (Version R17, November 2013). pmid:17311302 doi: 10.1002/humu.20495
[19]
Pleasance ED, Stephens PJ, O'Meara S, McBride DJ, Meynert A, Jones D, et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. 2010;463(7278):184–90. doi: 10.1038/nature08629. pmid:20016488
[20]
Pfeifer GP. How the environment shapes cancer genomes. Current opinion in oncology. 2015;27(1):71–7. doi: 10.1097/CCO.0000000000000152. pmid:25402978
[21]
Scelo G, Riazalhosseini Y, Greger L, Letourneau L, Gonzalez-Porta M, Wozniak MB, et al. Variation in genomic landscape of clear cell renal cell carcinoma across Europe. Nature communications. 2014;5:5135. doi: 10.1038/ncomms6135. pmid:25351205
[22]
Poon SL, Pang ST, McPherson JR, Yu W, Huang KK, Guan P, et al. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Science translational medicine. 2013;5(197):197ra01. doi: 10.1126/scitranslmed.3006086
[23]
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. doi: 10.1038/nature12477. pmid:23945592
[24]
Olivier M, Weninger A, Ardin M, Huskova H, Castells X, Vallee MP, et al. Modelling mutational landscapes of human cancers in vitro. Sci Rep. 2014;4:4482. doi: 10.1038/srep04482. pmid:24670820
[25]
Korte JE, Brennan P, Henley SJ, Boffetta P. Dose-specific meta-analysis and sensitivity analysis of the relation between alcohol consumption and lung cancer risk. Am J Epidemiol. 2002;155(6):496–506. pmid:11882523 doi: 10.1093/aje/155.6.496
[26]
Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta-carotene materially reduce human cancer rates? Nature. 1981;290(5803):201–8. pmid:7010181 doi: 10.1038/290201a0
[27]
Goralczyk R. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research. Nutr Cancer. 2009;61(6):767–74. doi: 10.1080/01635580903285155. pmid:20155614
[28]
Lawlor DA, Davey Smith G, Kundu D, Bruckdorfer KR, Ebrahim S. Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? Lancet. 2004;363(9422):1724–7. pmid:15158637 doi: 10.1016/s0140-6736(04)16260-0
[29]
Smith GD, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22. pmid:12689998 doi: 10.1093/ije/dyg070
[30]
Chen L, Smith GD, Harbord RM, Lewis SJ. Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med. 2008;5(3):e52. doi: 10.1371/journal.pmed.0050052. pmid:18318597
[31]
Thrift AP, Shaheen NJ, Gammon MD, Bernstein L, Reid BJ, Onstad L, et al. Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a mendelian randomization study. J Natl Cancer Inst. 2014;106(11). doi: 10.1093/jnci/dju252
[32]
Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, et al. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. J Natl Cancer Inst. 2015;107(9).
[33]
Trummer O, Pilz S, Hoffmann MM, Winkelmann BR, Boehm BO, Marz W, et al. Vitamin D and mortality: a Mendelian randomization study. Clinical chemistry. 2013;59(5):793–7. doi: 10.1373/clinchem.2012.193185. pmid:23319826
[34]
Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572–80. doi: 10.1016/S0140-6736(12)60312-2. pmid:22607825
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35. doi: 10.1016/S0140-6736(14)61177-6. pmid:25131982
[37]
Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age. PLoS Med. 2015;12(3):e1001779. doi: 10.1371/journal.pmed.1001779. pmid:25826379
[38]
Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89–98. doi: 10.1093/hmg/ddu328. pmid:25064373
[39]
Ebrahim S, Davey Smith G. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet. 2008;123(1):15–33. pmid:18038153 doi: 10.1007/s00439-007-0448-6
[40]
Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64. doi: 10.1093/ije/dyr036. pmid:21414999
[41]
VanderWeele TJ, Tchetgen Tchetgen EJ, Cornelis M, Kraft P. Methodological challenges in mendelian randomization. Epidemiology. 2014;25(3):427–35. doi: 10.1097/EDE.0000000000000081. pmid:24681576
[42]
Ferlay J SI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013 , accessed on 05-Mar-2015.
[43]
Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385(9972):977–1010. doi: 10.1016/S0140-6736(14)62038-9. pmid:25467588
[44]
Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372(23):2243–57. doi: 10.1056/NEJMsr1501341. pmid:26014596
[45]
Jervis S, Song H, Lee A, Dicks E, Harrington P, Baynes C, et al. A risk prediction algorithm for ovarian cancer incorporating BRCA1, BRCA2, common alleles and other familial effects. J Med Genet. 2015;52(7):465–75. doi: 10.1136/jmedgenet-2015-103077. pmid:26025000
[46]
Szulkin R, Whitington T, Eklund M, Aly M, Eeles RA, Easton D, et al. Prediction of individual genetic risk to prostate cancer using a polygenic score. Prostate. 2015. doi: 10.1002/pros.23037
[47]
Kreimer AR, Brennan P, Lang Kuhs KA, Waterboer T, Clifford G, Franceschi S, et al. Human papillomavirus antibodies and future risk of anogenital cancer: a nested case-control study in the European prospective investigation into cancer and nutrition study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2015;33(8):877–84. doi: 10.1200/jco.2014.57.8435
[48]
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nature medicine. 2008;14(9):985–90. doi: 10.1038/nm.1789. pmid:18670422
[49]
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Science translational medicine. 2014;6(224):224ra24. doi: 10.1126/scitranslmed.3007094. pmid:24553385
[50]
Iorio MV, Croce CM. microRNA involvement in human cancer. Carcinogenesis. 2012;33(6):1126–33. doi: 10.1093/carcin/bgs140. pmid:22491715
[51]
Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, et al. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2014;32(8):768–73. doi: 10.1200/jco.2013.50.4357
[52]
Bianchi F, Nicassio F, Marzi M, Belloni E, Dall'olio V, Bernard L, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO molecular medicine. 2011;3(8):495–503. doi: 10.1002/emmm.201100154. pmid:21744498
[53]
Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol. 2012;13(8):790–801. doi: 10.1016/S1470-2045(12)70211-5. pmid:22658655
[54]
Wild CP, Bucher JR, de Jong BW, Dillner J, von Gertten C, Groopman JD, et al. Translational cancer research: balancing prevention and treatment to combat cancer globally. J Natl Cancer Inst. 2015;107(1):353. doi: 10.1093/jnci/dju353. pmid:25515230
