Background A family history of colorectal cancer is recognizedas a risk factor for the disease. However, as a result of theretrospective design of prior studies, the strength of thisassociation is uncertain, particularly as it is influenced bycharacteristics of the person at risk and the affected familymembers.
Methods We conducted a prospective study of 32,085 men and 87,031women who had not previously been examined by colonoscopy orsigmoidoscopy and who provided data on first-degree relativeswith colorectal cancer, diet, and other risk factors for thedisease. During the follow-up period, colorectal cancer wasdiagnosed in 148 men and 315 women.
Results The age-adjusted relative risk of colorectal cancerfor men and women with affected first-degree relatives, as comparedwith those without a family history of the disease, was 1.72(95 percent confidence interval, 1.34 to 2.19). The relativerisk among study participants with two or more affected first-degreerelatives was 2.75 (95 percent confidence interval, 1.34 to5.63). For participants under the age of 45 years who had oneor more affected first-degree relatives, the relative risk was5.37 (95 percent confidence interval, 1.98 to 14.6), and therisk decreased with increasing age (P for trend, <0.001).
Conclusions A family history of colorectal cancer is associatedwith an increased risk of the disease, especially among youngerpeople.
Familial clustering of colorectal cancer is generally believedto occur even when the cases are not part of a defined geneticsyndrome. At least 12 retrospective studies have suggested thata history of colorectal cancer in a first-degree relative (aparent or sibling) elevates a person's lifetime risk of colorectalcancer 1.8-fold to 8.0-fold.1,2,3,4,5,6,7,8,9,10,11,12 However,the strength of the association is uncertain because of theretrospective design of these analyses and their failure tocontrol for other important risk factors.
In aggregate, prior analyses suggest that among people witha family history of colorectal cancer, those who are younger,those whose relatives received the diagnosis at a younger age,and those with two or more affected relatives are at particularlyhigh risk. On the basis of these findings, the American CancerSociety recommends that people with one or more first-degreerelatives who received a diagnosis of colorectal cancer at 55years of age or younger should undergo screening colonoscopyevery three to five years beginning at the age of 35 to 40 years.13In this analysis, we used data from two large prospective cohortstudies to quantify the excess risk of colorectal cancer associatedwith a family history of the disease and to assess the influenceof characteristics of the person at risk and of the affectedfamily members on this excess risk.
Methods
Study Cohorts
We analyzed data from two ongoing studies: the Nurses' HealthStudy and the Health Professionals Follow-up Study. The Nurses'Health Study began in 1976, when 121,700 U.S. women who wereregistered nurses, 30 to 55 years of age, completed a mailedquestionnaire on known or suspected risk factors for cancer14and coronary heart disease.15 In 1980 the questionnaire wasexpanded to include an assessment of diet. The Health ProfessionalsFollow-up Study began in 1986, when 51,269 U.S. men who weredentists, optometrists, osteopaths, pharmacists, podiatrists,or veterinarians, 40 to 75 years of age, completed a mailedquestionnaire on known or suspected risk factors for cancerand coronary heart disease, which also included an assessmentof diet.16 Every two years since these studies began, the participantshave been sent follow-up questionnaires to obtain updated informationon potential risk factors and recently diagnosed cases of cancerand other diseases.
Exposure Data
The study participants provided information on their smokinghistory, age, height, weight, physical activity, use of aspirin,and previous examination by colonoscopy or sigmoidoscopy, aswell as the indications for the procedure. A question aboutcolorectal cancer in a father, mother, sister, or brother wasincluded in the 1982 questionnaire for the women, and the informationwas updated in 1988. A question about colorectal cancer in afather or mother was included in the 1986 questionnaire forthe men. In 1990 the information on paternal or maternal colorectalcancer was updated, and a question about colorectal cancer ina sibling was included in the questionnaire for the men. Noquestions were asked about family size, and no attempt was madeto validate reports of cancer in family members.
The 1980 Nurses' Health Study questionnaire and the 1986 HealthProfessionals Follow-up Study questionnaire included semiquantitativequestions about food to assess diet as well as the use of supplementalvitamins. The subjects were asked to report the average frequencyof consumption of each listed food or nutrient during the previousyear. The reproducibility and validity of these questionnaireshave been documented elsewhere17,18,19,20,21.
Population for Analysis
We excluded women who left 10 or more questions about food itemsblank on the 1980 (61 item) food-frequency questionnaire, andwe excluded men who left 70 or more questions about food itemsblank on the 1986 (131 item) food-frequency questionnaire. Inaddition, women and men with implausibly high or low scoresfor total food intake were excluded. Both women and men whoreported previous cancer (other than nonmelanoma skin cancer),ulcerative colitis, or a familial polyposis syndrome were excluded.Since endoscopic examination and polypectomy can significantlyalter the natural history of colorectal cancer,22,23 we excludedparticipants with previous colonoscopic or sigmoidoscopic examinationsor colorectal adenomas before the study period. In addition,given the relatively high prevalence of endoscopic examinationsin the cohort of men, we excluded those who did not answer thequestions about endoscopy. Although the women who left the endoscopyquestions blank were included in the analysis, the exclusionof this group did not materially alter the relative risk ofcolorectal cancer associated with a family history of the diseasein the cohort of women. These exclusions left 87,031 women and32,085 men eligible for follow-up.
Identification of Cases of Colorectal Cancer
On each questionnaire we inquired whether colon or rectal cancerhad been diagnosed and, if so, the date of the diagnosis. Forthis analysis, the follow-up rate was 96 and 94 percent of totalpossible person-years for the Nurses' Health Study and the HealthProfessionals Follow-up Study, respectively. Most of the deathsin these cohorts were reported by family members or the PostalService in response to the follow-up questionnaires. In addition,we used the National Death Index, a highly sensitive methodof identifying deaths among nonrespondents.24 All participantswho reported colorectal cancer (or the next of kin for decedents)were contacted for permission to review the relevant hospitalrecords and confirm the diagnosis. Pathology reports were obtainedfor 92 and 89 percent of the cases among the women and men,respectively. Information on the histologic characteristics,stage, and anatomical location of the tumors was extracted fromthe reports by physicians who were unaware of the data on familyhistory and other risk factors reported by the study participants.Although pathology reports and hospital records could not beobtained for 8 and 11 percent of cases among the women and men,respectively, we based our analysis on the total number of reportedcolorectal cancers, because the rate of accuracy of self-reportingwas high (92 and 95 percent for the cohorts of women and men,respectively). We excluded the small number of cancers thatwere not adenocarcinomas, as well as carcinomas in situ. Thus,our analysis is based on the 315 cases of invasive colorectaladenocarcinoma among the women and the 148 cases among the men.
Statistical Analysis
For the primary analysis we used incidence rates, with person-yearsof follow-up as the denominator. For each participant, the person-yearsof follow-up were counted from the year when the questionnairethat contained the base-line data on family history was returned(1982 in the cohort of women and 1986 in the cohort of men)to May 31, 1990, for the women and January 31, 1992, for themen. For the participants in both cohorts who received a diagnosisof colorectal cancer or who died from another cause, the person-yearsof follow-up were calculated according to the most recentlycompleted questionnaire, but the period of follow-up terminatedwith the diagnosis of colorectal cancer or death. If no questionnairewas returned for a follow-up interval, the most recently recordeddata were used for the subsequent interval.
We used relative risk as a measure of association, defined asthe incidence of colorectal cancer among the study participantswith a family history of colorectal cancer, divided by the correspondingrate among the participants who had no family history of thedisease. Age-adjusted relative risks were calculated after stratificationaccording to five-year age categories. We used proportional-hazardsmodels to adjust for multiple risk factors simultaneously.25We conducted additional stratified analyses to evaluate theinfluence of characteristics of the study participants and affectedfamily members on the risk associated with a family historyof colorectal cancer. Tests for the homogeneity of risk estimatesacross strata were based on a weighted sum of the squared deviationsof the stratum-specific log-odds ratios from their weightedmean26.
To obtain stable estimates of the cumulative incidence of colorectalcancer among people with a family history of the disease, weused both estimates of relative risk from our analysis and incidencerates for the general population from the Surveillance, Epidemiology,and End Results (SEER) program. Although the SEER data basedoes not include family history, we assumed that the prevalenceof a family history of colorectal cancer among people with colorectalcancer in the SEER data base was similar to the prevalence ofa family history among people with colorectal cancer in ourcohorts. In addition, we assumed that the multivariate age-specificrelative risks associated with a family history were stablefor each five-year age category. Incidence rates within eachfive-year age category among study participants without a familyhistory were calculated according to the following formula:
incidence rateno family history = incidence rateSEER dividedby (Pno family history + [Pfamily history x relative riskfamilyhistory]),
where P denotes prevalence. We calculated incidence rates amongpeople with a family history of colorectal cancer by multiplyingthe multivariate age-specific relative risk associated witha family history by the incidence rate of colorectal canceramong people in the corresponding five-year age category whohad no family history of the disease. In the determination ofcumulative incidence rates, the study participants who werealive and free of colorectal cancer at the start of the five-yearinterval were considered to be at risk for the disease.
The proportion of all cases of colorectal cancer in each cohortthat were attributable to a family history of colorectal cancerwas calculated as the proportion of cases among those with afamily history that were attributable to a family history ([relativerisk - 1] divided by relative risk) multiplied by the prevalenceof a family history among the people with colorectal cancer26.
Results
A history of colorectal cancer in a first-degree relative wasreported by 3007 (9.4 percent) of the 32,085 men in the HealthProfessionals Follow-up Study and by 8727 (10.0 percent) ofthe 87,031 women in the Nurses' Health Study who were eligiblefor analysis. During the study period, colorectal cancer wasdiagnosed in 148 of the men and 315 of the women. Of these 463participants with colorectal cancer, 17 percent had previouslyreported a family history of colorectal cancer. Base-line characteristicsof the study participants according to the presence or absenceof a family history of colorectal cancer are shown in Table 1.Within each cohort, the patterns of dietary intake, body-massindex, level of physical activity, and smoking history weresimilar in the groups of participants with and without a familyhistory. In both cohorts, participants with a family historyof colorectal cancer underwent screening endoscopy during thestudy period more frequently than those without a family history.
Table 1. Characteristics of the Study Participants According to the Presence or Absence of a Family History of Colorectal Cancer.
Participants in the Health Professionals Follow-up Study andthe Nurses' Health Study who reported a history of colorectalcancer in one or more first-degree relatives had similarly increasedrisks of colorectal cancer. For men with a family history, theage-adjusted relative risk was 1.64 (95 percent confidence interval,1.04 to 2.58), and for women with a family history, the age-adjustedrelative risk was 1.77 (95 percent confidence interval, 1.32to 2.37) (Table 2). Furthermore, the relative risk associatedwith a family history of colorectal cancer was not materiallyaltered by multivariate adjustment for known or suspected environmentalrisk factors for the disease.
Table 2. Risk of Colorectal Cancer among Study Participants According to the Presence or Absence of a Family History of the Disease.
In both cohorts, the relative risk of colorectal cancer associatedwith a family history of the disease was higher for the youngerparticipants (Table 3). Among the women, for whom there weresubstantially more person-years of follow-up, the relative riskassociated with a family history was highest for those youngerthan 50 years of age, and the risk decreased progressively forolder women. This trend in the association between relativerisk and age among the women was significant (P = 0.005). Whenthe cohorts of men and women were combined, the results weresimilar. For participants younger than 45 years of age, therelative risk of colorectal cancer was 5.37 (95 percent confidenceinterval, 1.98 to 14.6), and the risk decreased monotonicallyfor older people. For participants 65 years of age or older,the relative risk associated with a family history approached1. These results remained essentially unchanged after otherrisk factors for colorectal cancer had been controlled for.For men and women combined, the linear trend of a decreasingrelative risk in association with increasing age was significant(P<0.001).
Table 3. Age-Specific Relative Risk of Colorectal Cancer among Study Participants with a Family History of Colorectal Cancer.
Our estimates of age-specific relative risk and incidence ratesfrom the SEER program were used to estimate the cumulative incidenceof colorectal cancer among people with a family history of thedisease and those without a family history (Figure 1). Partlyon the basis of data on the age-specific cumulative incidenceof colorectal cancer, the National Cancer Institute, AmericanCancer Society, American College of Physicians, American GastroenterologicalAssociation, and World Health Organization all recommend screeningsigmoidoscopy beginning at the age of 50 years for Americanswith an average risk of the disease.13 For people with a familyhistory of colorectal cancer, we found a similar cumulativeincidence of the disease at approximately 35 to 40 years ofage.
Figure 1. Cumulative Incidence of Colorectal Cancer According to Age and the Presence or Absence of a Family History of the Disease.
We also examined the association between the risk of colorectalcancer and the type and number of affected first-degree relatives.The type of affected relative (mother, father, or sibling) didnot have a significant influence on the relative risk (P = 0.75for the test of the homogeneity of odds ratios).
Among the men who reported two or more affected first-degreerelatives, there were no cases of colorectal cancer (Table 4).This finding may reflect the small number of men who had twoor more affected relatives and had not undergone screening endoscopybefore the start of the study (543 person-years of follow-upfor a total of 176,093 person-years for the entire cohort).Among the women with two or more affected first-degree relatives,the age-adjusted relative risk of colorectal cancer was 3.79(95 percent confidence interval, 1.88 to 7.62); the linear trendtoward an increase in relative risk with the increasing numberof affected relatives was significant (P<0.001). Even whenthe cohorts of men and women were combined, the relative riskfor people with two or more affected relatives was 2.75 (95percent confidence interval, 1.34 to 5.63; P for trend, <0.001).
Table 4. Relative Risk of Colorectal Cancer According to the Number of Affected Relatives.
In both cohorts, a family history of colorectal cancer was associatedwith an excess risk of colon cancer but not of rectal cancer(Table 5). Among men and women combined, the age-adjusted relativerisk of colon cancer was l.99 (95 percent confidence interval,1.51 to 2.61) and the age-adjusted relative risk of rectal cancerwas 0.86 (95 percent confidence interval, 0.44 to 1.70). Adjustmentfor various known or suspected environmental risk factors forcolorectal cancer did not materially change these results, andthe risk estimates for colon and rectal cancer differed significantly(P = 0.02). The site of disease within the colon had no significantassociation with the relative risk.
Table 5. Risk of Colorectal Cancer among Study Participants According to the Specific Site of the Disease.
We investigated the possibility that the excess risk associatedwith a family history of colorectal cancer was the result ofa detection bias caused by closer surveillance of people witha family history of the disease. When we excluded from the analysismen and women whose cancers may have been detected incidentallyor only by screening (Dukes' stages A and B), the multivariaterelative risk of colorectal cancer associated with a familyhistory did not decrease (relative risk, 2.00; 95 percent confidenceinterval, 1.32 to 3.03). Moreover, when we restricted our analysisto fatal colorectal cancers among the study participants, therelative risk was 1.72 (95 percent confidence interval, 1.03to 2.89).
Discussion
This prospective analysis found a consistent increase in therisk of colorectal cancer among men and women with a familyhistory of the disease. The increase in risk, which was about1.7-fold, was virtually identical in cohorts from two independentlyconducted studies, and the risk increased significantly if therewas a history of two or more affected relatives. The effectof family history was greatest for people who were 44 yearsof age or younger; a family history of the disease was not associatedwith a significant elevation in risk among people 60 years orolder, although we had limited power to determine risk estimatesfor people over the age of 75. Within the combined cohorts,7 percent of all cases of colorectal cancer were attributableto a family history in a first-degree relative, and 23 percentof colorectal cancers diagnosed in cohort members under theage of 45 years were attributable to a family history of thedisease.
The prospective nature of this study substantially reduces thepossibility of a recall bias, a potential source of distortionthat is inherent in retrospective studies of family historyand the risk of cancer. Data on family history were obtainedonly from the study participants; we did not ask relatives toverify these reports, and we did not determine family size.Since the participants were all health care professionals, theaccuracy of the reports is likely to be high. Moreover, becausethe data on family history were collected before the diagnosisof any cases of colorectal cancer, any errors in recall wouldhave attenuated rather than exaggerated a true association.Familial clusters that may have occurred simply because of largefamilies would also have attenuated our results.
Other forms of bias are unlikely to explain the observed relations.To minimize the possibility of a selection bias, we excludedpeople who had undergone either polypectomy or endoscopy beforethe start of our analysis. Such people were more likely to reporta family history of colorectal cancer (14.5 percent), and thosewith a family history had a markedly attenuated excess riskof disease, which is consistent with the presumed effect ofendoscopy on the natural history of colorectal neoplasia (datanot shown).
Differential follow-up is unlikely to have had a material influence,since follow-up was nearly complete for both fatal and nonfatalend points. A detection bias also appears unlikely, since theassociation between relative risk and family history persistedwhen the analysis was restricted to either advanced or fatalcases of colorectal cancer. Finally, since new cases of cancermay develop in relatives during follow-up in a prospective study,we used updated information on family history to minimize misclassification.
Previous studies that have addressed the relation between familyhistory and the risk of colorectal cancer used retrospectivedata. The relative risk associated with a family history ofthe disease has varied considerably, although estimates in thethree largest case-control studies ranged from 1.8 to 2.14,9,10.In these three studies, investigators reported an increasedrisk of colorectal cancer among people with two or more affectedrelatives4,10 and an increased risk among people with a familyhistory who were younger than 50 years of age,4,9 findings consistentwith ours. In support of other recent observations, our analysisrefutes the tenet that the familial predisposition to coloncancer is associated predominantly with tumors that have a proximalsite of origin4,9,10,27. Although we observed an increased riskof colon cancer but not of rectal cancer, we were unable todetect a difference in risk according to the specific site ofthe tumor within the colon.
Previous analyses have been unable to distinguish between geneticand common environmental contributions to familial clusteringof colorectal cancer. However, kindred studies suggest thatfamilial clustering of common (i.e., apparently sporadic) colorectalcancer probably occurs as a result of a partially penetrantinherited susceptibility.28 In the present analysis, the excessrisk associated with a family history did not change materiallyafter adjustment for other known or suspected risk factors forcolorectal cancer, which is consistent with the existence ofan important genetic contribution.
In conclusion, for the majority of people with a family historyof colorectal cancer, particularly those who are 60 years orolder, the excess risk of colorectal cancer is not large. Nevertheless,the increased risk among younger people with a family historysupports the recommendation of the American Cancer Society thatpeople with a family history of colorectal cancer undergo earlierscreening.
Supported by grants (CA 40935 and CA 55075) from the NationalInstitutes of Health. Dr. Fuchs is the recipient of the IrvingW. Jannock Fellowship and support from the Harvard EducationProgram in Cancer Prevention. Dr. Colditz is the recipient ofa Faculty Research Award (FRA-398) from the American CancerSociety.
Source Information
From Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (C.S.F., E.L.G., G.A.C., D.J.H., F.E.S., W.C.W.); the Division of Medical Oncology, Dana-Farber Cancer Institute (C.S.F.); and the Departments of Epidemiology (G.A.C., D.J.H., F.E.S., W.C.W.), Environmental Health (F.E.S.), and Nutrition (W.C.W.), Harvard School of Public Health -- all in Boston.
Address reprint requests to Dr. Fuchs at the Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115.
References
Bonelli L, Martines H, Conio M, Bruzzi P, Aste H. Family history of colorectal cancer as a risk factor for benign and malignant tumors of the large bowel: a case-control study. Int J Cancer 1988;41:513-517. [Medline]
Duncan JL, Kyle J. Family incidence of carcinoma of the colon and rectum in north-east Scotland. Gut 1982;23:169-171. [Free Full Text]
Fisher G, Armstrong B. Familial colorectal cancer and the screening of family members. Med J Aust 1989;150:22-25. [Medline]
Kune GA, Kune S, Watson LF. The role of heredity in the etiology of large bowel cancer. World J Surg 1989;13:124-129. [CrossRef][Medline]
Lovett E. Family studies in cancer of the colon and rectum. Br J Surg 1976;63:13-18. [Medline]
Macklin MT. Inheritance of cancer of the stomach and large intestine in man. J Natl Cancer Inst 1960;24:551-571.
Maire P, Morichau-Beauchant M, Drucker J, Barboteau MA, Barbier J, Matuchansky C. Prevalence familiale du cancer du colon et du rectum: resultats d'une enquete "cas-temoins" de 3 ans. Gastroenterol Clin Biol 1984;8:22-27. [Medline]
Ponz de Leon M, Antonioli A, Ascari A, Zanghieri G, Sacchetti C. Incidence and familial occurrence of colorectal cancer and polyps in a health-care district of northern Italy. Cancer 1987;60:2848-2859. [CrossRef][Medline]
Sondergaard JO, Bulow S, Lynge E. Cancer incidence among parents of patients with colorectal cancer. Int J Cancer 1991;47:202-206. [Medline]
St John DJ, McDermott FT, Hopper JL, Debney EA, Johnson WR, Hughes ES. Cancer risk in relatives of patients with common colorectal cancer. Ann Intern Med 1993;118:785-790. [Free Full Text]
Stephenson BM, Finan PJ, Gascoyne J, Garbett F, Murday VA, Bishop DT. Frequency of familial colorectal cancer. Br J Surg 1991;78:1162-1166. [Medline]
Woolf CM. A genetic study of carcinoma of the large intestine. Am J Hum Genet 1958;10:42-47.
Levin B, Murphy GP. Revision in American Cancer Society recommendations for the early detection of colorectal cancer. CA Cancer J Clin 1992;42:296-299. [Medline]
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Speizer FE. Moderate alcohol consumption and the risk of breast cancer. N Engl J Med 1987;316:1174-1180. [Abstract]
Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 1985;313:1044-1049. [Abstract]
Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-1456. [Free Full Text]
Colditz GA, Willett WC, Stampfer MJ, et al. The influence of age, relative weight, smoking, and alcohol intake on the reproducibility of a dietary questionnaire. Int J Epidemiol 1987;16:392-398. [Free Full Text]
Colditz GA, Martin P, Stampfer MJ, et al. Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol 1986;123:894-900. [Free Full Text]
Giovannuci E, Colditz G, Stampfer MJ, et al. The assessment of alcohol consumption by a simple self-administered questionnaire. Am J Epidemiol 1991;133:810-817. [Free Full Text]
Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51-65. [Free Full Text]
Willett WC, Sampson L, Browne ML, et al. The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol 1988;127:188-199. [Free Full Text]
Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329:1977-1981. [Free Full Text]
Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653-657. [Abstract]
Stampfer MJ, Willett WC, Speizer FE, et al. Test of the National Death Index. Am J Epidemiol 1984;119:837-839. [Free Full Text]
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986.
Cannon-Albright LA, Thomas TC, Bishop DT, Skolnick MH, Burt RW. Characteristics of familial colon cancer in a large population data base. Cancer 1989;64:1971-1975. [CrossRef][Medline]
Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med 1988;319:533-537. [Abstract]
Bapat, B., Lindor, N. M., Baron, J., Siegmund, K., Li, L., Zheng, Y., Haile, R., Gallinger, S., Jass, J. R., Young, J. P., Cotterchio, M., Jenkins, M., Grove, J., Casey, G., Thibodeau, S. N., Bishop, D. T., Hopper, J. L., Ahnen, D., Newcomb, P. A., Le Marchand, L., Potter, J. D., Seminara, D., and the Colon Cancer Family Registry,
(2009). The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer. Cancer Epidemiol. Biomarkers Prev.
18: 967-975
[Abstract][Full Text]
Freedman, A. N., Slattery, M. L., Ballard-Barbash, R., Willis, G., Cann, B. J., Pee, D., Gail, M. H., Pfeiffer, R. M.
(2009). Colorectal Cancer Risk Prediction Tool for White Men and Women Without Known Susceptibility. JCO
27: 686-693
[Abstract][Full Text]
Chan, J. A., Fuchs, C. S.
(2008). Family History and Survival in Patients With Stage III Colorectal Cancer--Reply. JAMA
300: 1996-1997
[Full Text]
Zell, J. A., Honda, J., Ziogas, A., Anton-Culver, H.
(2008). Survival After Colorectal Cancer Diagnosis Is Associated with Colorectal Cancer Family History. Cancer Epidemiol. Biomarkers Prev.
17: 3134-3140
[Abstract][Full Text]
Chan, J. A., Meyerhardt, J. A., Niedzwiecki, D., Hollis, D., Saltz, L. B., Mayer, R. J., Thomas, J., Schaefer, P., Whittom, R., Hantel, A., Goldberg, R. M., Warren, R. S., Bertagnolli, M., Fuchs, C. S.
(2008). Association of Family History With Cancer Recurrence and Survival Among Patients With Stage III Colon Cancer. JAMA
299: 2515-2523
[Abstract][Full Text]
Ladabaum, U.
(2007). When even people at high risk do not take up colorectal cancer screening. Gut
56: 1648-1650
[Full Text]
Ruthotto, F, Papendorf, F, Wegener, G, Unger, G, Dlugosch, B, Korangy, F, Manns, M., Greten, T.
(2007). Participation in screening colonoscopy in first-degree relatives from patients with colorectal cancer. Ann Oncol
18: 1518-1522
[Abstract][Full Text]
Ahuja, N., Chang, D., Gearhart, S. L.
(2007). Disparities in Colon Cancer Presentation and In-Hospital Mortality in Maryland: A Ten-Year Review. Ann. Surg. Oncol.
14: 411-416
[Abstract][Full Text]
Setoguchi, S., Glynn, R. J., Avorn, J., Mogun, H., Schneeweiss, S.
(2007). Statins and the Risk of Lung, Breast, and Colorectal Cancer in the Elderly. Circulation
115: 27-33
[Abstract][Full Text]
Aaltonen, L., Johns, L., Jarvinen, H., Mecklin, J.-P., Houlston, R.
(2007). Explaining the Familial Colorectal Cancer Risk Associated with Mismatch Repair (MMR)-Deficient and MMR-Stable Tumors. Clin. Cancer Res.
13: 356-361
[Abstract][Full Text]
Winawer, S. J., Zauber, A. G., Fletcher, R. H., Stillman, J. S., O'Brien, M. J., Levin, B., Smith, R. A., Lieberman, D. A., Burt, R. W., Levin, T. R., Bond, J. H., Brooks, D., Byers, T., Hyman, N., Kirk, L., Thorson, A., Simmang, C., Johnson, D., Rex, D. K.
(2006). Guidelines for Colonoscopy Surveillance after Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.. CA Cancer J Clin
56: 143-159
[Abstract][Full Text]
Taylor, W. C.
(2006). A 71-Year-Old Woman Contemplating a Screening Colonoscopy. JAMA
295: 1161-1167
[Full Text]
Dove-Edwin, I., Sasieni, P., Adams, J., Thomas, H. J W
(2005). Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 year, prospective, follow-up study. BMJ
331: 1047-
[Abstract][Full Text]
Ramsey, S. D., Burke, W., Pinsky, L., Clarke, L., Newcomb, P., Khoury, M. J.
(2005). Family History Assessment to Detect Increased Risk for Colorectal Cancer: Conceptual Considerations and a Preliminary Economic Analysis. Cancer Epidemiol. Biomarkers Prev.
14: 2494-2500
[Abstract][Full Text]
Eisen, G. M., Weinberg, D. S.
(2005). Narrative Review: Screening for Colorectal Cancer in Patients with a First-Degree Relative with Colonic Neoplasia. ANN INTERN MED
143: 190-198
[Abstract][Full Text]
Chan, A. T., Ma, J., Tranah, G. J., Giovannucci, E. L., Rifai, N., Hunter, D. J., Fuchs, C. S.
(2005). Hemochromatosis Gene Mutations, Body Iron Stores, Dietary Iron, and Risk of Colorectal Adenoma in Women. JNCI J Natl Cancer Inst
97: 917-926
[Abstract][Full Text]
Schoenfeld, P., Cash, B., Flood, A., Dobhan, R., Eastone, J., Coyle, W., Kikendall, J. W., Kim, H. M., Weiss, D. G., Emory, T., Schatzkin, A., Lieberman, D., the CONCeRN Study Investigators,
(2005). Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia. NEJM
352: 2061-2068
[Abstract][Full Text]
Eberl, M. M., Sunga, A. Y., Farrell, C. D., Mahoney, M. C.
(2005). Patients with a Family History of Cancer: Identification and Management. J Am Board Fam Med
18: 211-217
[Abstract][Full Text]
Coggins, R P, Cawkwell, L, Bell, S M, Crockford, G P, Quirke, P, Finan, P J, Bishop, D T
(2005). Association between family history and mismatch repair in colorectal cancer. Gut
54: 636-642
[Abstract][Full Text]
Rawl, S. M., Menon, U., Champion, V. L., May, F. E., Loehrer, P. Sr, Hunter, C., Azzouz, F., Monahan, P. O., Skinner, C. S.
(2005). Do benefits and barriers differ by stage of adoption for colorectal cancer screening?. Health Educ Res
20: 137-148
[Abstract][Full Text]
Murff, H. J., Spigel, D. R., Syngal, S.
(2004). Does This Patient Have a Family History of Cancer?: An Evidence-Based Analysis of the Accuracy of Family Cancer History. JAMA
292: 1480-1489
[Abstract][Full Text]
Andrieu, N, Launoy, G, Guillois, R, Ory-Paoletti, C, Gignoux, M
(2004). Estimation of the familial relative risk of cancer by site from a French population based family study on colorectal cancer (CCREF study). Gut
53: 1322-1328
[Abstract][Full Text]
Liljegren, A., Lindgren, G., Brandberg, Y., Rotstein, S., Nilsson, B., Hatschek, T., Jaramillo, E., Lindblom, A.
(2004). Individuals With an Increased Risk of Colorectal Cancer: Perceived Benefits and Psychological Aspects of Surveillance by Means of Regular Colonoscopies. JCO
22: 1736-1742
[Abstract][Full Text]
Sharp, L., Little, J.
(2004). Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review. Am J Epidemiol
159: 423-443
[Abstract][Full Text]
Lieberman, D. A., Prindiville, S., Weiss, D. G., Willett, W.
(2003). Risk Factors for Advanced Colonic Neoplasia and Hyperplastic Polyps in Asymptomatic Individuals. JAMA
290: 2959-2967
[Abstract][Full Text]
Murphy, K. M., Geiger, T., Hafez, M. J., Eshleman, J. R., Griffin, C. A., Berg, K. D.
(2003). A Single Nucleotide Primer Extension Assay to Detect the APC I1307K Gene Variant. J. Mol. Diagn.
5: 222-226
[Abstract][Full Text]
Liljegren, A, Lindblom, A, Rotstein, S, Nilsson, B, Rubio, C, Jaramillo, E
(2003). Prevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: correlation between the two types of colon polyps. Gut
52: 1140-1147
[Abstract][Full Text]
Almendingen, K, Hofstad, B, Vatn, M H
(2003). Does a family history of cancer increase the risk of occurrence, growth, and recurrence of colorectal adenomas?. Gut
52: 747-751
[Abstract][Full Text]
Liu, H.-X., Zhou, X.-L., Liu, T., Werelius, B., Lindmark, G., Dahl, N., Lindblom, A.
(2003). The Role of hMLH3 in Familial Colorectal Cancer. Cancer Res.
63: 1894-1899
[Abstract][Full Text]
Walsh, J. M. E., Terdiman, J. P.
(2003). Colorectal Cancer Screening: Clinical Applications. JAMA
289: 1297-1302
[Abstract][Full Text]
Janda, M., Stanton, W. R., Hughes, K., Del Mar, C., Clavarino, A., Aitken, J. F., Tong, S., Short, L., Leggett, B., Newman, B.
(2003). Knowledge, Attitude and Intentions Related to Colorectal Cancer Screening Using Faecal Occult Blood Tests in a Rural Australian Population. Asia Pac J Public Health
15: 50-56
[Abstract]
Brauer, P. M., McKeown-Eyssen, G. E., Jazmaji, V., Logan, A. G., Andrews, D. F., Jenkins, D., Marcon, N., Saibil, F., Cohen, L., Stern, H., Baron, D., Greenberg, G., Diamandis, E., Kakis, G., Singer, W., Steiner, G.
(2002). Familial Aggregation of Diabetes and Hypertension in a Case-Control Study of Colorectal Neoplasia. Am J Epidemiol
156: 702-713
[Abstract][Full Text]
Dunlop, M G
(2002). Guidance on large bowel surveillance for people with two first degree relatives with colorectal cancer or one first degree relative diagnosed with colorectal cancer under 45 years. Gut
51: v17-20
[Full Text]
Easson, A. M., Cotterchio, M., Crosby, J. A., Sutherland, H., Dale, D., Aronson, M., Holowaty, E., Gallinger, S.
(2002). A Population-Based Study of the Extent of Surgical Resection of Potentially Curable Colon Cancer. Ann. Surg. Oncol.
9: 380-387
[Abstract][Full Text]
Fuchs, C. S., Willett, W. C., Colditz, G. A., Hunter, D. J., Stampfer, M. J., Speizer, F. E., Giovannucci, E. L.
(2002). The Influence of Folate and Multivitamin Use on the Familial Risk of Colon Cancer in Women. Cancer Epidemiol. Biomarkers Prev.
11: 227-234
[Abstract][Full Text]
Sandhu, M S, Luben, R, Khaw, K-T
(2001). Self reported non-insulin dependent diabetes, family history, and risk of prevalent colorectal cancer: population based, cross sectional study. J. Epidemiol. Community Health
55: 804-805
[Full Text]
Hemminki, K., Li, X., Dong, C.
(2001). Second Primary Cancers after Sporadic and Familial Colorectal Cancer. Cancer Epidemiol. Biomarkers Prev.
10: 793-798
[Abstract][Full Text]
Renehan, A. G., O'Dwyer, S. T., Shalet, S. M.
(2000). RESPONSE: More About: Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3. JNCI J Natl Cancer Inst
92: 1949a-1949a
[Full Text]
Renehan, A. G., Bhaskar, P., Painter, J. E., O’Dwyer, S. T., Haboubi, N., Varma, J., Ball, S. G., Shalet, S. M.
(2000). The Prevalence and Characteristics of Colorectal Neoplasia in Acromegaly. J. Clin. Endocrinol. Metab.
85: 3417-3424
[Abstract][Full Text]
Syngal, S., Schrag, D., Falchuk, M., Tung, N., Farraye, F. A., Chung, D., Wright, M., Whetsell, A., Miller, G., Garber, J. E.
(2000). Phenotypic Characteristics Associated With the APC Gene I1307K Mutation in Ashkenazi Jewish Patients With Colorectal Polyps. JAMA
284: 857-860
[Abstract][Full Text]
Lieberman, D. A., Weiss, D. G., Bond, J. H., Ahnen, D. J., Garewal, H., Chejfec, G., Harford, W. V., Provenzale, D., Sontag, S., Schnell, T., Durbin, T. E., Nelson, D. B., Ewing, S. L., Triadafilopoulos, G., Ramirez, F. C., Lee, J. G., Collins, J. F., Fennerty, M. B., Johnston, T. K., Corless, C. L., McQuaid, K. R., Sampliner, R. E., Morales, T. G., Fass, R., Smith, R., Maheshwari, Y., The Veterans Affairs Cooperative Study Group 380,
(2000). Use of Colonoscopy to Screen Asymptomatic Adults for Colorectal Cancer. NEJM
343: 162-168
[Abstract][Full Text]
Gazelle, G. S., McMahon, P. M., Scholz, F. J.
(2000). Screening for Colorectal Cancer. Radiology
215: 327-335
[Abstract][Full Text]
Baier, M., Calonge, N., Cutter, G., McClatchey, M., Schoentgen, S., Hines, S., Marcus, A., Ahnen, D.
(2000). Validity of Self-Reported Colorectal Cancer Screening Behavior. Cancer Epidemiol. Biomarkers Prev.
9: 229-232
[Abstract][Full Text]
Schoen, R. E., Tangen, C. M., Kuller, L. H., Burke, G. L., Cushman, M., Tracy, R. P., Dobs, A., Savage, P. J.
(1999). Increased Blood Glucose and Insulin, Body Size, and Incident Colorectal Cancer. JNCI J Natl Cancer Inst
91: 1147-1154
[Abstract][Full Text]
Glanz, K., Grove, J., Le Marchand, L., Gotay, C.
(1999). Underreporting of Family History of Colon Cancer: Correlates and Implications. Cancer Epidemiol. Biomarkers Prev.
8: 635-639
[Abstract][Full Text]
Petersen, G. M., Larkin, E., Codori, A.-M., Wang, C.-Y., Booker, S. V., Bacon, J., Giardiello, F. M., Boyd, P. A.
(1999). Attitudes toward Colon Cancer Gene Testing: Survey of Relatives of Colon Cancer Patients. Cancer Epidemiol. Biomarkers Prev.
8: 337-344
[Abstract][Full Text]
Codori, A.-M., Petersen, G. M., Miglioretti, D. L., Larkin, E. K., Bushey, M. T., Young, C., Brensinger, J. D., Johnson, K., Bacon, J. A., Booker, S. V.
(1999). Attitudes toward Colon Cancer Gene Testing: Factors Predicting Test Uptake. Cancer Epidemiol. Biomarkers Prev.
8: 345-351
[Abstract][Full Text]
Brown, S R, Finan, P J, Bishop, D T
(1998). Are relatives of patients with multiple HNPCC spectrum tumours at increased risk of cancer?. Gut
43: 664-668
[Abstract][Full Text]
Dunlop, M., Campbell, H.
(1997). Screening for people with a family history of colorectal cancer. BMJ
314: 1779-1779
[Full Text]
Mulcahy, H. E, Farthing, M. J G, O'Donoghue, D. P
(1997). Fortnightly review: screening for asymptomatic colorectal cancer. BMJ
314: 285-285
[Full Text]
Winawer, S. J., Zauber, A. G., Gerdes, H., O'Brien, M. J., Gottlieb, L. S., Sternberg, S. S., Bond, J. H., Waye, J. D., Schapiro, M., Panish, J. F., Kurtz, R. C., Shike, M., Ackroyd, F. W., Stewart, E. T., Skolnick, M., Bishop, D. T., The National Polyp Study Workgroup,
(1996). Risk of Colorectal Cancer in the Families of Patients with Adenomatous Polyps. NEJM
334: 82-87
[Abstract][Full Text]
Narod, S. A., Ginsburg, O., Jothy, S., Selby, J. V., Fuchs, C. S., Willett, W. C.
(1995). Family History and Colorectal Cancer. NEJM
332: 1578-1579
[Full Text]
