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Together with observations that tumours in the hereditary cancer syndromes HNPCC and FAP occur predominantly in the right and left colon, respectively, the existence of 2 categories of CRC based on site of origin in the large bowel was proposed more than a decade ago. Differences between normal right and left colonic segments that could favour progression through different tumourigenic pathways are summarized in this review. Accumulating evidence suggests that the risk of CRC conferred by various environmental and genetic factors is different for proximal and distal tumours. Right\u2010 and left\u2010sided tumours also exhibit different sensitivities to fluorouracil\u2010based chemotherapy. Such differences are probably related to the molecular characteristics of the tumours, with the microsatellite instability and CpG island methylator phenotypes being associated with right\u2010sided tumours and chromosomal instability with left\u2010sided tumours. Future molecular\u2010based classification systems for CRC that rely upon distinctive gene expression patterns may allow a clearer discrimination of subgroups than that provided by tumour site alone. Until then however, the existence of 2 broadly different groups of cancer defined by site of origin in the colon should be considered in the design of future epidemiologic studies as well as in the design of new clinical trials aimed at testing novel adjuvant therapies. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10635","type":"journal-article","created":{"date-parts":[[2002,10,8]],"date-time":"2002-10-08T22:57:58Z","timestamp":1034117878000},"page":"403-408","source":"Crossref","is-referenced-by-count":643,"title":["Are there two sides to colorectal cancer?"],"prefix":"10.1002","volume":"101","author":[{"given":"Barry","family":"Iacopetta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,9,3]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199002083220602"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-113-10-779"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02553382"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890515)63:10<1888::AID-CNCR2820631004>3.0.CO;2-L"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1985.237"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90537-0"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jso.2930440109"},{"key":"e_1_2_9_10_2","first-page":"10","article-title":"Two colons\u2014two cancers? 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