Abstract
Obesity and cancer have been found to have a direct link in epidemiological studies. Obesity raises the risk of cancer and associated chronic disorders. Furthermore, an imbalance of adipokines, like leptins, plays a crucial role in neoplasm pathogenesis, cell migration, and thereby, cancer metastasis. Also, leptin increases human epidermal growth factor receptor 2 (HER2) protein levels through the STAT3-mediated (signal transducer and activator of transcription) upregulation of heat shock protein (Hsp90) in breast cancer cells. It has been noticed that insulin and insulin-like growth factors (IGFs) act as mitosis activators in the host and cancerous breast epithelial cells. The condition of hyperinsulinemia explains the positive association between colorectal cancer and obesity. Furthermore, in prostate cancer, an alteration in sex hormone levels, testosterone and dihydrotestosterone, has been reported to occur, along with increased oxidative stress, which is the actual cause of the tumors. Whereas, there have been two interconnected factors that play a crucial role in the psychological cycle concerned with lung cancer. The review article focuses on all the prospects of etiological mechanisms that have found linkage with obesity and breast, colon, lung, and prostate cancers. Furthermore, the article has also highlighted how these new insights into the processes occur and, due to which reasons, obesity contributes to tumorigenesis. This review provides a detailed discussion on the progression, which can assist in the development of new and innovative techniques to interfere in this process, and it has been supported with insights based on evidence literature on approved clinical treatments for obesity and cancer.
Keywords: Obesity, epidemiology, body mass index, cancer, etiological mechanisms, leptins, STAT3-mediated, clinical trials.
[http://dx.doi.org/10.1093/carcin/21.3.485] [PMID: 10688869]
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.1016/S0098-2997(00)00007-8] [PMID: 11173079]
[http://dx.doi.org/10.7314/APJCP.2012.13.10.4873] [PMID: 23244073]
[http://dx.doi.org/10.1053/j.gastro.2007.03.052] [PMID: 17498505]
[http://dx.doi.org/10.1038/nrc1408] [PMID: 15286738]
[http://dx.doi.org/10.3322/caac.21440] [PMID: 29160902]
[http://dx.doi.org/10.1136/bmj.j477] [PMID: 28246088]
[http://dx.doi.org/10.1038/s41388-018-0592-6] [PMID: 30518876]
[http://dx.doi.org/10.1155/2013/291546] [PMID: 24073332]
[http://dx.doi.org/10.1016/S0140-6736(08)60269-X] [PMID: 18280327]
[http://dx.doi.org/10.1056/NEJMoa021423] [PMID: 12711737]
[http://dx.doi.org/10.2741/E596] [PMID: 23481261]
[http://dx.doi.org/10.1371/journal.pmed.1000058] [PMID: 19399161]
[http://dx.doi.org/10.3390/ijms14011629] [PMID: 23344060]
[http://dx.doi.org/10.1038/nm.3112] [PMID: 23603815]
[http://dx.doi.org/10.1152/physrev.00033.2011] [PMID: 23303913]
[http://dx.doi.org/10.1016/j.cell.2007.10.004] [PMID: 17956727]
[http://dx.doi.org/10.3390/ijms20153657] [PMID: 31357412]
[http://dx.doi.org/10.1038/ijo.2008.102] [PMID: 18607383]
[http://dx.doi.org/10.1016/S0140-6736(14)60460-8] [PMID: 24880830]
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0057] [PMID: 24819876]
[http://dx.doi.org/10.1016/j.biocel.2015.06.010] [PMID: 26073129]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0183] [PMID: 25122071]
[http://dx.doi.org/10.1038/nm.2492] [PMID: 22037646]
[http://dx.doi.org/10.1016/j.bbalip.2013.02.010] [PMID: 23500888]
[http://dx.doi.org/10.1111/j.1749-6632.2012.06737.x] [PMID: 23050968]
[http://dx.doi.org/10.1074/jbc.M609798200] [PMID: 17344214]
[http://dx.doi.org/10.18632/oncotarget.5561] [PMID: 26472027]
[http://dx.doi.org/10.1074/jbc.M304984200] [PMID: 12902351]
[http://dx.doi.org/10.1002/jcp.20472] [PMID: 16110483]
[http://dx.doi.org/10.1080/15384101.2015.1041684] [PMID: 26017929]
[http://dx.doi.org/10.1038/sj.bjc.6604166] [PMID: 18182989]
[http://dx.doi.org/10.1677/ERC-07-0065] [PMID: 17914101]
[http://dx.doi.org/10.1016/j.cell.2009.11.027] [PMID: 20079333]
[http://dx.doi.org/10.3389/fgene.2012.00268] [PMID: 23226157]
[http://dx.doi.org/10.3390/cancers12123798] [PMID: 33339340]
[http://dx.doi.org/10.1016/j.cmet.2013.04.012] [PMID: 23663740]
[http://dx.doi.org/10.1371/journal.pone.0208099] [PMID: 30730895]
[http://dx.doi.org/10.1096/fj.13-232868] [PMID: 24277575]
[http://dx.doi.org/10.1080/14728222.2018.1538356] [PMID: 30332900]
[http://dx.doi.org/10.1515/hmbci-2014-0037] [PMID: 25781552]
[http://dx.doi.org/10.3389/fendo.2014.00065] [PMID: 24829560]
[http://dx.doi.org/10.1074/jbc.270.45.26746] [PMID: 7592907]
[http://dx.doi.org/10.1161/01.CIR.102.11.1296] [PMID: 10982546]
[http://dx.doi.org/10.3389/fonc.2020.615375] [PMID: 33604295]
[http://dx.doi.org/10.1200/JCO.2016.67.9712] [PMID: 27903152]
[http://dx.doi.org/10.1111/j.1749-6632.2012.06750.x] [PMID: 23050962]
[http://dx.doi.org/10.1200/JCO.2008.19.8937] [PMID: 19064959]
[http://dx.doi.org/10.1007/s11912-010-0139-7] [PMID: 21080117]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2755] [PMID: 19074892]
[http://dx.doi.org/10.1007/s10549-006-9471-x] [PMID: 17221153]
[http://dx.doi.org/10.1056/NEJMra050776] [PMID: 16421368]
[http://dx.doi.org/10.1038/nrm3025] [PMID: 21157483]
[http://dx.doi.org/10.1038/nbt.2942] [PMID: 24997786]
[http://dx.doi.org/10.1097/PPO.0000000000000049] [PMID: 24855004]
[http://dx.doi.org/10.1016/j.metabol.2018.11.001] [PMID: 30445141]
[http://dx.doi.org/10.1155/2021/6620873] [PMID: 34104309]
[http://dx.doi.org/10.1007/s11684-019-0695-7] [PMID: 31250341]
[http://dx.doi.org/10.1111/nyas.12416] [PMID: 24725147]
[http://dx.doi.org/10.3390/nu13103656] [PMID: 34684657]
[http://dx.doi.org/10.1038/nrgastro.2017.72] [PMID: 28676707]
[http://dx.doi.org/10.1158/1055-9965.EPI-14-0240] [PMID: 25012997]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.077602] [PMID: 22156000]
[http://dx.doi.org/10.1002/bjs.9623] [PMID: 25224741]
[http://dx.doi.org/10.1073/pnas.1100255108] [PMID: 21876127]
[PMID: 26236690]
[http://dx.doi.org/10.1111/micc.12270] [PMID: 26808917]
[http://dx.doi.org/10.1161/01.RES.0000099243.20096.FA] [PMID: 14525808]
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[http://dx.doi.org/10.1038/s41586-018-0040-3] [PMID: 29670281]
[http://dx.doi.org/10.1126/science.aaf4405] [PMID: 27124451]
[http://dx.doi.org/10.1158/1940-6207.CAPR-12-0140] [PMID: 23034147]
[http://dx.doi.org/10.1146/annurev.pathmechdis.3.121806.151434] [PMID: 18039139]
[http://dx.doi.org/10.3389/fonc.2017.00078] [PMID: 28491820]
[http://dx.doi.org/10.1016/S2214-109X(19)30488-7] [PMID: 31862245]
[http://dx.doi.org/10.1677/erc.1.00729] [PMID: 16728564]
[http://dx.doi.org/10.1016/j.gendis.2020.12.005] [PMID: 35782984]
[http://dx.doi.org/10.1207/S15327914NC4501_1] [PMID: 12791499]
[http://dx.doi.org/10.3389/fonc.2019.00765] [PMID: 31555578]
[http://dx.doi.org/10.1210/en.2009-0070] [PMID: 19372199]
[http://dx.doi.org/10.1186/s12943-015-0291-7] [PMID: 25743390]
[http://dx.doi.org/10.1016/j.bbadis.2019.165660] [PMID: 31891805]
[http://dx.doi.org/10.1111/j.1365-2036.2007.03371.x] [PMID: 17593063]
[http://dx.doi.org/10.1016/j.ccell.2018.03.004] [PMID: 29657127]
[http://dx.doi.org/10.1016/j.eururo.2012.11.013] [PMID: 23219374]
[http://dx.doi.org/10.1097/MOU.0000000000000424] [PMID: 28632505]
[http://dx.doi.org/10.1530/EC-15-0080] [PMID: 26581226]
[http://dx.doi.org/10.1016/j.prnlm.2015.08.001] [PMID: 27014656]
[http://dx.doi.org/10.1186/s40248-016-0066-z] [PMID: 27408717]
[http://dx.doi.org/10.1111/j.1467-789X.2006.00261.x] [PMID: 17038127]
[http://dx.doi.org/10.1007/s10549-021-06355-9] [PMID: 34383179]
[http://dx.doi.org/10.1158/1940-6207.CAPR-18-0262] [PMID: 31818851]
[http://dx.doi.org/10.1038/s41391-022-00492-y] [PMID: 35079115]
[http://dx.doi.org/10.1002/oby.22347] [PMID: 30421844]
[http://dx.doi.org/10.1016/S2213-8587(20)30364-8] [PMID: 33137293]
[http://dx.doi.org/10.1136/jim-2021-001952] [PMID: 34706925]