Editing Carcinogen (section)

===Colon cancer===

[[Colorectal cancer]] is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)].<ref name=Ferlay /> Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States.<ref>{{cite journal | vauthors = Giovannucci E, Martínez ME | title = Tobacco, colorectal cancer, and adenomas: a review of the evidence | journal = Journal of the National Cancer Institute | volume = 88 | issue = 23 | pages = 1717–1730 | date = December 1996 | pmid = 8944002 | doi = 10.1093/jnci/88.23.1717 | doi-access =  }}</ref>  In addition, substantial evidence implicates [[bile acid]]s as an important factor in colon cancer.  Twelve studies (summarized in Bernstein et al.<ref name=Bernstein2009>{{cite journal | vauthors = Bernstein H, Bernstein C, Payne CM, Dvorak K | title = Bile acids as endogenous etiologic agents in gastrointestinal cancer | journal = World Journal of Gastroenterology | volume = 15 | issue = 27 | pages = 3329–3340 | date = July 2009 | pmid = 19610133 | pmc = 2712893 | doi = 10.3748/wjg.15.3329 | doi-access = free }}</ref>) indicate that the bile acids deoxycholic acid (DCA) or lithocholic acid (LCA) induce production of DNA-damaging reactive oxygen species or reactive nitrogen species in human or animal colon cells.  Furthermore, 14 studies showed that DCA and LCA induce DNA damage in colon cells.  Also 27 studies reported that bile acids cause programmed cell death ([[apoptosis]]).

Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis.<ref name=Bernstein2009 />  Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer.<ref name=Bernstein2009 />  Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer.  Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids.  When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months.<ref>{{cite journal | vauthors = Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H | title = Carcinogenicity of deoxycholate, a secondary bile acid | journal = Archives of Toxicology | volume = 85 | issue = 8 | pages = 863–871 | date = August 2011 | pmid = 21267546 | pmc = 3149672 | doi = 10.1007/s00204-011-0648-7 | bibcode = 2011ArTox..85..863B }}</ref>  Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer.