Hereditary CRC has two well-described forms: familial adenomatous polyposis (FAP, including an attenuated form of polyposis [AFAP]), due to germline mutations in the APC gene,[52,53,54,55,56,57,58,59] and Lynch syndrome (LS) (also called hereditary nonpolyposis colorectal cancer [HNPCC]), which is caused by germline mutations in DNA MMR genes.[60,61,62,63] Many other families exhibit aggregation of CRC and/or adenomas, but with no apparent association with an identifiable hereditary syndrome, and are known collectively as familial CRC.
Difficulties in Identifying a Family History of CRC Risk
The accuracy and completeness of family history data must be taken into account in using family history to assess individual risk in clinical practice, and in identifying families appropriate for cancer research. A reported family history may be erroneous, or a person may be unaware of relatives with cancer. In addition, small family sizes and premature deaths may limit how informative a family history may be. Also, some persons may carry a genetic predisposition to CRC but do not develop cancer, giving the impression of skipped generations in a family tree.
When family histories of colon cancer were checked in a research study, a sensitivity of 73% (95% CI, 54–86) was obtained. In this study of Utah patients, the investigators compared self-reported family history of colon cancer with a computerized Utah Population Database, which was created by linking genealogical records with the state cancer registry. The kappa score, a measure of overall agreement between the reported family history and the database, was 0.56 (95% CI, 0.45–0.66), indicating moderately good agreement. Thus, what patients tell clinicians about their family histories is a reasonably good indicator of actual history.
Other Risk Factors for CRC
Other risk factors that may influence the development of adenomatous polyps and CRC risk include diet, use of nonsteroidal anti-inflammatory drugs (NSAIDs), postmenopausal hormone use, cigarette smoking, colonoscopy with removal of adenomatous polyps, and physical activity.
- Dietary factors that appear to be associated with developing adenomatous polyps and an increased incidence of CRC risk include a diet high in total fat [66,67,68] and meat (both red and white meat).[68,69,70,71,72,73,74,75,76,77,78,79]
- Some,[80,81,82] but not all, studies have reported an association between aspirin use and decreased adenomatous polyp development and colon cancer incidence. In addition, studies have suggested a decreased risk of colon cancer among users of postmenopausal female hormone supplements.[84,85]
- Cigarette smoking is associated with an increased tendency to form adenomas that develop into CRC.[86,87]
- Colonoscopy with removal of adenomatous polyps reduces the risk of CRC.
- A sedentary lifestyle has been associated in some,[88,89,90] but not all, studies with an increased risk of CRC.