The large intestine, also known as the colon, is vulnerable to the development of cancer due to its rapid turnover and exposure to toxins. Colon cancer is the second most prevalent cancer in men in the United States, and the third most prevalent in women after lung and breast cancer. The incidence of colon cancer may become even more significant as the incidence of lung cancer decreases due to a decrease in cigarette smoking. Colon cancer occurs when the normal genetic control over the rate of epithelial cell proliferation is disrupted, leading to the growth of polyps that can eventually become invasive tumors and metastasize to other parts of the body. The underlying molecular defects in colon cancer can vary, including overexpression of growth-stimulatory factors or mutations that prevent cells from responding to growth-suppressive factors. However, early detection and removal of polyps with malignant potential can substantially reduce colon cancer mortality. Current guidelines recommend increased screening for colon abnormalities, even in asymptomatic middle-aged individuals, through colonoscopy or non-invasive imaging techniques. In the colon, three transport processes play a role in driving absorption. The first process involves electroneutral NaCl absorption, which is stimulated by growth factors and inhibited by hormones and neurotransmitters that increase cAMP levels in colonic surface epithelial cells. The second process is the absorption of short-chain fatty acids, such as acetate, propionate, and butyrate, which are absorbed by surface epithelial cells through sodium-monocarboxylate transporters (SMCTs). The uptake of these fatty acids is driven by the low intracellular sodium levels maintained by the basolateral Na+,K+-ATPase. Short-chain fatty acids are used for energy by colonocytes and can also regulate gene expression and potentially suppress malignant transformation. However, reduced expression of SMCT1 in some colon cancers leads to a decrease in butyrate uptake, which may contribute to malignant transformation. The third major absorptive process in the colon involves the absorption of sodium ions.
Thecolonicepitheliumturnsoverrapidlyinhealth,thuslimitingtheaccumulationofgeneticdamage.However,thisrapidturnover,aswellasfrequent/prolongedexposuretobacteriallysynthesizedorenvironmentaltoxins,orboth,makesthelargeintestineespeciallyvulnerabletomalignancy.ColoncancerissecondinprevalenceonlytolungcancerinmenintheUnitedStatesandthirdbehindlungandbreastcancerinwomen.Withthedecreasedincidenceofcigarettesmokingandthereforelungcancer,coloncancermayassumeevengreatersignificance.Coloncancerariseswhennormalgeneticcontrolsontherateofepithelialproliferationaresubverted;initiallythisleadstogrowthofapolypandeventually,ifnotremoved,toaninvasivetumorthatmaymetastasizetootherpartsofthebody.Coloncancercanbesubdividedaccordingtothebasicnatureoftheunderlyingmoleculardefect,whichcanincludeoverexpressionofgrowthstimulatoryfactorsoramutationthatpreventsthecellsfromrespondingtofactorsthatwouldnormallybegrowthsuppressive.However,coloncancermortalitycanbereducedverysubstantiallybyearlydetectionandremovalofpolypswithmalignantpotential.Thishasdrivencurrentguidelinesforincreasedscreeningofevenasymptomaticmiddle-agedindividualsforcolonicabnormalitiesviacolonoscopy(inwhichaflexiblefiberoptictubeisinsertedintothecolontoinspectitsinterior),screeningforthepresenceofso-calledoccult(orhidden)bloodinthestoolderivedfromableedingpolyportumor,ornoninvasiveimagingtechniquessuchascomputedtomographyscans.
colon is driven by three transport processes. The first is electroneutral NaCl absorption, which is mediated by the same mechanism that drives NaCl absorption in the intestine (see
Fig. 30.17 ). NaCl absorption is stimulated by various growth factors, such as epidermal growth factor, and is inhibited by hormones and neurotransmitters that increase levels of cyclic adenosine monophosphate (cAMP) in colonic surface epithelial cells.
•Fig. 31.4 Mechanismofshort-chainfattyacid(SCFA)uptakebycolonocytes.ATP,adenosinetriphosphate;SMCT1,sodium/monocarboxylatecotransporter1.3Na˜SMCT1 SCFA used by colonocyte for intracellular metabolism ATP
The second transport process that drives fluid absorption in the colon is absorption of short-chain fatty acids, including acetate, propionate, and butyrate. These molecules are absorbed from the lumen by surface (and perhaps crypt) epithelial cells in an Na+-dependent fashion by a family of symporters related to the Na+-glucose symporter in the small intestine, and known as sodium-monocarboxylate transporters (SMCTs). Uptake of short-chain fatty acids by SMCTs located in the apical plasma membrane is driven by the low intracellular [Na+] established by the basolateral Na+,K+-ATPase (
Fig. 31.4 ). These short-chain fatty acids are used for energy by colonocytes. In addition, butyrate regulates expression of specific genes in colonic epithelial cells and may suppress development of a malignant phenotype. Expression of SMCT1 (also identified as SLC5A8) is reduced in some colon cancers, thereby leading to a reduction in butyrate uptake, which may contribute to malignant transformation.
The third absorptive process of major significance in the colon is absorption of Na+ (