The Impact of Family History of Colon Cancer on Survival after Diagnosis with Colon Cancer

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1 International Journal of Epidemiology O International Epfdemlotoglcal Association 1995 Vol. 24, No. 5 Printed In Great Britain The Impact of Family History of Colon Cancer on Survival after Diagnosis with Colon Cancer MARTHA L SLATTERY AND RICHARD A KERBER Slattery M L (Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA) and Kerber R A. The impact of family history of colon cancer on survival after diagnosis with colon cancer. International Journal of Epidemiology 1995; 24: Background. The impact of family history of colon cancer on survival after diagnosis with colon cancer is generally unknown. It is possible that family history Is indicative of a genetically inherited form of disease which may alter survival. Methods. The Utah Population Database was used to evaluate survival after diagnosis with colon cancer among 2236 first primary colon cancer cases. This database includes detailed information about family history and is linked to the Utah Cancer Registry to obtain tumour information. Results. Stage at diagnosis was the primary factor associated with death from all causes and from colon cancer. An older age at diagnosis, being female, and having a tumour in the ascending segment of the colon also were associated with poorer survival, although after adjusting for stage at diagnosis these associations disappeared. Having a family history of colon cancer had little impact on survival patterns although there were suggestions that men who were diagnosed.at age <55 were more likely to die from all causes as well as colon cancer If they had a sibling with colon cancer (hazard rate ratio [HRR] 2.50, 95% confidence interval [Cl] : ) relative to men >55 without a sibling with colon cancer. Conclusions. From these data it appears that the major factor which Increases survival Is being diagnosed at an early stage of disease. These data also suggest that younger men who have a sibling with colon cancer may have a different form of colon cancer which increases their risk of dying. Keywords, colonic neoplasia, family history of cancer, survival Factors which influence survival after diagnosis with cancer are not well understood. While most research has focused on treatment methods which may influence survival, little is known about factors which are intrinsic to the individual, including family history of cancer and lifestyle, and their impact on survival. Family history has been evaluated as a factor which could influence survival with breast cancer.'" 5 However little is known about the impact of family history of colon cancer on survival after diagnosis with colon cancer. One study 5 showed that those with hereditary colon cancer had slightly better survival than those without a family history of colon cancer and that those diagnosed at a younger age had better survival. 5 ' 6 Likewise, individuals whose tumours have various genetic alterations have been shown to have different survival patterns. 7 Thus, it is possible that genetic factors which are associated with and expressed as a positive family history of the disease may influence survival once diagnosed. Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. 888 In this study we use the Utah Population Database (UPDB), a linked database which consists of genealogy data and Utah Cancer Registry (UCR) data to examine survival patterns of people diagnosed with colon cancer. With this database we have access to detailed family history information which in some instances goes back seven generations. METHODS In this study we include 2236 cases (1114 women and 1122 men) of first primary colon cancer recorded in the Utah Cancer Registry (UCR) with a date of diagnosis after 1965 and who link to the UPDB genealogy database. The UCR is a population-based registry of cancers occurring in Utah. In 1966, the cancer registry began collecting tumour information throughout the state; in 1972 it became part of the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) Program. Data from the UCR have been linked to the genealogy database, a computerized database that contains family information on over one million

2 COLON CANCER SURVIVAL 889 descendants of the Utah pioneers. 8 ' 9 Records from the UCR were linked to the UPDB database via probabilistic record-linking software developed by RAK. Last, first, and middle names, parts of names, dates of birth and death, and place of birth were used to link records. Records with ambiguous linking scores were hand checked. For married women, marriage records from the UPDB genealogy were used to generate married names, and second and third names given in cancer registry record were evaluated as possible maiden names. The percentage of colon cancer records linked to the genealogy database was 43.1% for men and 43.0% for women. In general, the proportion of cancer records linked to the genealogy decreased with increasing birth year, particularly for women. No differences in stage of disease at diagnosis were observed between linked and unlinked cases. Data obtained from the UCR included the age at diagnosis, the total number of months survived, the date of last observation, vital status, site of the tumour at diagnosis, and stage of the tumour at diagnosis. 10 The SEER summary stage codes were used to evaluate the impact of disease stage at diagnosis on survival. These codes take into account the tumour size and extent, node involvement, and metastasis. Tumours at a local stage are those which invade the submucosa or muscularis propria, have no lymph node involvement, and no metastasis. Tumours defined as regional invade through the muscularis propria into the subserosa or into non-peritonealized pericolic or perirectal tissues, or perforate the visceral peritoneum or other organs or structures such as small intestine, abdominal fat wall or enterperitenoneum; they have no lymph node involvement or metastasis. Distant tumours are those which invade other more distant organs such as the gallbladder, diaphragm, or adrenal glands, have lymph node involvement and distant metastasis. Tumour registry data were used to estimate length of survival. Genealogy data were used to develop family history profiles. Together these data were used to determine familial risk estimates of colon cancer and their impact on survival. Family History Definitions Family history was defined several ways. The most comprehensive family history measure we used was the familial standardized incidence ratio (FSIR). This measure takes into account the variability in family size and person-time at risk among the families of subjects. It weights the observed familial cancer rates by kinship to the subject."' 12 We also have defined family history by kinship order, including first, second, third, and fourth and greater kinship ranking. Firstdegree relatives include mothers, fathers, children, brothers and sisters, second-degree relatives include grandparents and aunts and uncles, third-degree relatives include first cousins and great grandparents, fourth-degree relatives include second cousins, greatgreat grandparents, great aunts and uncles, and more distant relatives. We further examine type of firstdegree relative with cancer since much of the reported literature has focused on the first-degree relative. Statistical Analyses Familial risk calculation. Familial risk was calculated as a familial standardized incidence ratio (FSIR). For each subject we did a comprehensive search of all the subject's relatives (ascending, descending, and collateral), and calculated observed and expected cases of colon and other cancers within six age- and sex-specific categories. Both observed and expected cancer counts were weighted by a kinship coefficient which measures the probability that the subject and his or her relative share a random gene through common descent. After all relatives were searched, FSIR was calculated by summing observed and expected cases across age and sex categories, and dividing total observed by total expected." Other statistical methods. The distribution of the population in terms of having a family history of colon cancer was assessed. We also evaluated the sex-specific survival associations and other factors which could be associated with survival, including the age at diagnosis, stage at diagnosis, and the site of the tumour within the colon. Proximal or ascending tumours were defined as tumours in the caecum, ascending, hepatic flexure and transverse segments of the colon; distal or descending tumours included those located in the splenic flexure, descending and sigmoid parts of the colon. The months of observation were calculated from the month of diagnosis until the month of death. Months of observation for people still alive or lost to follow-up were counted from the date of diagnosis until the date of last contact. We calculated median survival times, using the product-limit (Kaplan-Meier) estimate. 13 Median survival times are presented as the time in which 50% of the population had either died from any cause, were censored as alive, or were censored at the date of last contact. Brookmeyer-Crowley 95% confidence intervals (CI) on the median survival times are presented along with Breslow estimates of differences in survival between groups (BMDP). We used Cox proportional hazard techniques to estimate hazard rate ratios (HRR)

3 890 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY and corresponding 95% CI associated with family history. In these analyses we took into account stage at diagnosis and age at diagnosis. We excluded people for whom stage of diagnosis was unknown (N = 201) from the proportional hazards models. We stratified the data by age at diagnosis (S55 and >55). We estimated survival for deaths from all causes and for deaths from colon cancer only. When evaluating deaths from colon cancer only, we censored deaths from other causes. RESULTS Of the 1114 women and 1122 men diagnosed with colon cancer, 72.0% (802) of the women and 71.8% (806) of the men had died. For both women and men, the primary cause of death reported was colon cancer accounting for 458 (57.1%) deaths among women and 402 (49.9%) deaths among men. Other cancers accounted for 9.9% of deaths (n = 79) among women and 11.7% (n = 94) among men. The most frequently occurring other cancer deaths for women were rectal cancer (11 or 1.4% of deaths), other gastrointenstinal cancers (13 or 1.6% of deaths), and unknown primary (18 or 2.2% of deaths). Among men, the most frequently occurring other deaths from cancer were rectal cancer (11 or 1.4% of deaths), other gastrointenstinal cancers (18 or 2.2% of deaths), unknown primary (17 or 2.1% of deaths), cancers of the gallbladder, lung, or prostate (8 each or 1% of deaths each). The primary factors associated with crude survival include age, stage of disease at diagnosis, and tumour site within the colon (Table 1). The median survival was less among older men and women, those diagnosed at a more advanced stage of disease, and those whose tumour was located in the ascending segment of the colon. Among men, those with a higher familial risk score had better crude survival than those with less of a family history. We also characterized survival by short-term survival (=S24 months) and by longer-term survival (Table 2). We observed that among women, those >65 years at the time of diagnosis, those diagnosed at a more distant stage of disease, and those with tumours in the ascending segment of the colon were more likely to die within 24 months of diagnosis. Evaluation of a family history of colon cancer did not show any associations with survival. The most pronounced indicator of risk of death from all causes and from colon cancer was diagnosis at a late stage of disease. The HRR of dying from any cause was approximately 8 and for dying from colon cancer was 13 when diagnosed at a distant stage of disease relative to diagnosis at a local stage of disease. After adjustment for stage of disease and age at diagnosis, there were no differences in risk of dying for men versus women or ascending versus descending tumours. Family history of colon cancer did not appear to alter one's risk of dying from any cause or from colon cancer in either men or women when examining all ages combined (Table 3). We further evaluated the age at which diagnosis occurred and risk of dying if one had a family history of colon cancer (Table 4). Among women age >55 and men =S55 years, we observed that risk of dying from colon cancer increased if a sibling had colon cancer. Among younger men, a twofold increase in risk of death was observed if their sibling had been diagnosed with colon cancer relative to younger men without a sibling with colon cancer. No alteration in risk was observed if parents had colon cancer. Findings were similar for all-cause mortality as for deaths from colon cancer. We further evaluated the interaction between age at diagnosis, sex, and having a sibling with colon cancer and survival (Table 5). We observed that men diagnosed at age *55 with a sibling with colon cancer had a relative risk of 2.50 of dying of any cause (95% CI : ) compared to men >55 without a sibling with colon cancer. The HRR for younger women with a sibling with colon cancer was 1.10 (95% CI: ). Similar interactions were observed when analysing deaths from colon cancer. Stage at diagnosis was a major factor associated with survival. We therefore examined factors which might be associated with stage at which the tumour is diagnosed (Table 6). We found that more men than women were diagnosed at a local stage and that stage was unknown for more women than men. Among cases >65, the stage was unknown more frequently than for younger people. Tumours in the descending segment of the colon were more frequently diagnosed at an earlier stage. These associations were observed for both men and women. The only indicator of family history associated with stage of diagnosis was having a sibling with colon cancer which was associated with an earlier diagnosis. Overall, the association between stage at diagnosis and having a sibling with colon cancer was of borderline significance (P = 0.08) when tumours at an unknown stage were included and significant (P = 0.04) when those tumours with an unknown stage were excluded. When examining sex-specific associations similar findings were observed. DISCUSSION Lifestyle and family history of cancer could potentially alter survival if environmental and genetic factors

4 COLON CANCER SURVIVAL 891 TABLE 1 Description of study population Median survival time (95% CI)* Dead(N9t>) Censored (N») Dead(N%) Censored (N%) Total Sex (27, 37) 39 (33, 44) Age at diagnosis S >65 (Breslow) Stage at diagnosis' 1 Local Regional Distant / -value (Breslow) Site of tumour in the colon 0 Ascending Descending (Breslow) (Breslow) (Breslow) (Breslow) < -1.9 (Breslow) 32 (4.0) 167 (20.8) 603 (75.2) 180 (26.0) 273 (39.5) 238 (34.4) 364 (52.0) 336 (48.0) 788 (98.2) 14(1.7) 746 (93.0) 56 (7.0) 70 (8.7) 43 (5.4) 105(13.1) 584 (72.8) 479 (59.7) 150(18.7) 109(13.6) 64 (8.0) 33 (10.6) 98(31.4) 181 (58.0) 154(51.3) 138(46.0) 8 (2.7) 115(38.7) 182(61.3) 303(97.1) 9 (2.9) 291 (93.3) 21 (6.7) 29 (9.3) 18(5.8) 45(14.4) 220 (70 5) 176(56.4) 63 (20.2) 43 (13.8) 30 (9.6) 37 (4.6) 197 (24.4) 572(7) 189 (25.6) 326 (44.2) 223 (30.2) 343 (47.4) 381 (52.6) 788 (97.8) 18 (2.2) 745 (92.4) 61 (7.6) 77 (9.6) 47 (5.8) 126(15.6) 556 (69.0) 466 (57.8) 148(18.4) 131 (16.3) 61 (7.6) 32(10.1) 116(36.7) 168 (53.2) 176 (57.5) 120 (39.2) 10(3.3) 120 (40.4) 177 (59.6) 309 (97.8) 7 (2.2) 295 (93.3) 21 (6.6) 27 (8.5) 19 (6.0) 50(15.8) 220 (70.0) 183 (57.9) 63(19.9) 45(14.2) 25 (7.9) 93 (39, -) 53(38,71) 24 (20, 29) 109(89, 131) 50 (40, 58) 6 (5, 7) 29 (22, 34) 49 (38, 66) 32 (26, 37) 38(14,-) (26, 36) 41 (18,57) (19,57) 52(21,87) 24(16,39) 32 (26, 38) (28, 42) 25(18,36) 27(17,50) 42 (24, 59) (25,-) 64 (46, 86) 30 (26, 35) 118(96, 143) 42 (36, 54) 6 (5, 6) 30(21,38) 50(40,61) 38 (32, 44) 59(12,76) (32, 43) 52(27,71) (29,71) 30 (20, 70) 34 (22, 48) 39 (32, 46) (30, 42) 32 (22, 46) 48 (30, 57) 65 (37, 90) (43,-) 58 (46, 71) 27 (24, 30) 113(103, 129) 47 (39, 53) 6 (5, 6) 29 (24, 33) 49 (42, 60) 35(31,38) 55 (20, 76) (31,38) 42 (27, 59) (29, 57) 39 (27, 70) 30 (22, 39) 35(31,38) (29, 57) 39 (27, 70) 30 (22, 39) 35(31,38) 0.29 ' Median survival time in months. 95* confidence interval (Cl) calculated by Brookmeyer-Crowly. If ties in data occur, CI cannot be calculated. b Stage at diagnosis unknown for 78 men and 123 women. c Site of tumour unknown for 101 men and 117 women.

5 892 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY TABLE 2 Characteristics of study population by length of survival in months <24 Months Survival time Months >60 Months Sex / -value (47.9) (42.7) (20.0) (24.6) (32.0) (32.7) Age at diagnosis < >65 Stage at diagnosis* Local Regional Distant Site of tumour in the colon b Ascending Descending < (35.1) (35.3) (50.0) (21.6) (35.8) (87.7) (48.9) (37.7) (45.4) (39.6) (45.6) (41.5) (40.9) (41.7) (50.3) (45.1) (45.2) (49.3) (44.5) (46.7) (20.9) (23.7) (21.9) (26.5) (29.1) (7.7) (23.3) (23.8) (22.3) (25.0) (22.2) (23.9) (24.1) (24.4) (19.0) (22 6) (22.3) (2) (22.3) (21.9) (44.0) (4) (28.1) (51.9) (35.1) (4.6) (27.7) (38.5) (32.3) (35.4) (32.2) (34.6) (30.9) (33.9) (30.7) (32.3) (32.4) (29.7) (33.2) (31.4) "Excludes 201 with unknown stage. b Excludes 218 with unknown site.

6 COLON CANCER SURVIVAL 893 TABLE 3 Hazard rate ratio (HRRf for family history for all causes mortality and from colon cancer by family history All causes Colon cancer All causes Colon cancer < ( ) 1.19 ( ) 0.97 ( ) 0.91 ( ) 1.13 ( ) 0.92 ( ) 1.14 ( ) 1.12 ( ) 0.82 ( ).0 ().83 ( ) ( ).09 ( ) 8 ( ) 1 ( ) 1.10 ( ).0.11 ( ).15 ( ).06 ( ) 0.90 ( ).0.12 ( ) 1.37 (3-1.83).07 ( ) 6 ( ) 0.99 ( ) ' HRR calculated from Cox proportional hazard models and adjusted for age and stage at diagnosis. influence the disease. Using data from the UPDB we evaluated the impact of a family history of colon cancer on survival once diagnosed. We observed that having a sibling with colon cancer had an impact on survival which was influenced by gender and age at diagnosis. who were age = 55 at the time of diagnosis were more likely to die (from any cause or colon cancer) if they had a sibling with colon cancer. We did not observe an increase in risk for having a parent with colon cancer, although there were few people in this database who had a parent with colon cancer. These findings are opposite to those which we observed for breast cancer, where we observed that having a sibling with breast cancer increased survival while having a parent with breast cancer decreased survival. 3 Results from this study suggest that there are different survival patterns within certain subgroups of those who develop colon cancer. Despite the fact that those with a sibling were generally diagnosed at an earlier stage of disease, survival was worse among men = 55 if they had a sibling with colon cancer after controlling for stage at diagnosis. This may indicate a genetically different form of colon cancer which is more severe, or shared environmental factors which may act differently given an inherited genetic predisposition to colon cancer. Differences in risk by age at diagnosis and sex have been observed for colon cancer development. l4tl5 Descriptive data suggest differences in colon cancer 0.89 ( ) 0.98 ( ) 1.22 ( ) 2 ( ) 0.98 ( ) 1.26 ( ) 0.94 ( ) 0.84 ( ) incidence by age and sex and analytical data support these observations. It has been shown in some studies that diet carries less risk among men diagnosed at a younger versus older age while reproductive factors may differ in their relationship to risk of colon cancer by age at diagnosis. 14 " 16 These differences observed in aetiology may contribute to different forms of disease and thus the different survival patterns for young and old men and women which we observed. Although marginally significant, the increased risk of death among younger men with an affected sibling might conceivably be a chance observation. As has been shown by others 6 the major factor affecting survival is stage at diagnosis, with those diagnosed at a more advanced stage being more likely to die. Thus, early detection is probably the major contributor to better survival. Although we do not have data on screening practices of the population, we were able to examine factors which could be associated with stage of the tumour at diagnosis. We observed that men were more likely to be diagnosed at an earlier stage of disease than were women. Likewise, tumours in the descending segment of the colon were more likely to be detected at an early stage than were tumours in the ascending segment of the colon. People with a sibling with colon cancer were more likely to be diagnosed at an earlier stage, while having a parent with colon cancer did not alter the stage at diagnosis. The differential effect on survival of site of the tumour, age at

7 894 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY TABLE 4 Hazard rate ratio (HRR) associated with family history for all causes of mortality and colon cancer mortality by age at diagnosis All causes Colon cancer All causes Colon cancer Age at diagnosis >55 years < -1 9 Age at diagnosis <55 years < ( ) 1.19 ( ) 0.89 ( ) 0.88 ( ) 1.12 ( ) 0.88 ( ) 3 ( ) 1 15 ( ) 0.77 ( ) 5 ( ) 0.94 ( ) 0.87 ( ) 1.66 ( ) 1.46 ( ) 1.89 ( ) 0.56 ( ) 0.74 ( ) 1.29 ( ) 3 ( ) ( ) 1.16 ( ) 0.83 ( ) 1.31 ( ) 1.15 ( ) 6 ( ) _b 1.36 ( ) 0.80 ( ) 0.59 ( ) 1.55 ( ) 1.62 ( ) 0.23 ( ) * HRR calculated from Cox proportional hazard models and adjusted for age and stage at diagnosis. 'Unable to calculate since no one had died who had a sibling with colon cancer. diagnosis, and sex was the result of stage at diagnosis, although these differences could have implications for screening practices. In summary, we observed that having a family history of colon cancer had little impact on survival patterns, except among men ^55 years of age who had a sibling with colon cancer. Stage of the tumour at diagnosis was the major factor associated with survival. There are indications in these data that women are diagnosed when tumours have advanced to a more distant stage. While this may be partly attributed to women having a slighter greater percentage of their tumours in the ascending segment of the colon, 12 this also could be an indication that women have screening sigmoidoscopies less frequently resulting 0.83 ( ) 4 ( ) 6 ( ) 1.12 ( ) 1 ( ) 6 ( ) 1 ( ) ( ) 0.64 ( ) 2.33 ( ) 1.48 ( ) 0.98 ( ) 1.41 ( ) 1.75 ( ) 1.38 ( ) 0.56 ( ) 0.84 ( ) 0.88 ( ) 1.19 ( ) 0.96 ( ) 0.88 ( ) 1.22 ( ) 0.90 ( ) 0.83 ( ) 7 ( ) 2.35 ( ) 1.37 ( ) 1.29 ( ) 1.81 ( ) 1.67 ( ) 1.26 ( ) 0.80 ( ) TABLE 5 Interaction between age at diagnosis, having a sibling with colon cancer, and sex and risk of dying of any cause Age at diagnosis >55 years <55 years Sex Male Female Male Female with colon cancer No Yes No Yes No Yes No Yes 1 06( ) 0.90(0.80-) 8( ) 6( ) 2.50(3-6.10) 0.% ( ) 1.10( )

8 COLON CANCER SURVIVAL 895 TABLE 6 Characteristics of the population by stage at diagnosis Local Regional Stage at diagnosis Distant Unknown N * N % N % N 5, Sex /"-valne Age at diagnosis <5O >65 / -value Site of tumour in the colon* Asceoding Descending < 'Excludes 218 people with unknown site O < CO (30.0) (32.5) (29.9) (33.9) (30.4) (28.1) (35.9) (31.3) (31.3) (30.6) (40.3) (38.4) (27.6) (31.9) (30.5) (30.0) (30.7) (35.1) (35.0) in the tumour being at a more advanced stage at detection. ACKNOWLEDGEMENTS This research was supported by grant CA and contract CN05222 from the National Cancer Institute. We would like to thank Rosemary Dibble of the Utah Cancer Registry and Christi Ramsey for their assistance in the preparation of this manuscript. REFERENCES 1 Ruder A M, Moodie P F, Nelson N A, Choi N W. Does family history of breast cancer improve survival among patients with breast cancer? Am J Obstet Cynecol 1988; 158: (36.9) (39.8) (44.0) (40.1) (37.1) (42.6) (37.8) (38.4) (35.4) (38.6) (34.6) (35.0) (46.5) (37.4) (38.3) (38.0) (39.6) (36.0) (42.2) (22.1) (20.8) (21.6) (21.3) (21.5) (24.5) (21.2) (21.3) (27.1) (21.8) (17.0) (19.2) (15.7) (23.6) (21.7) (22.2) (21.2) (2) (17.2) (1) (7.0) (4.5) (4.7) (1) (4.8) (5 2) (9.0) (6.3) (9.1) (8.2) (7.4) (10.2) (7.1) (9.5) (9.9) (8.5) (7.9) (5.6) 2 Anderson D E, Badzioch M D. Survival in familial breast cancer patients. Cancer 1986; 58: Slattery M L, Berry D T, Kerber R A. Is survival among women diagnosed with breast cancer influenced by family history of cancer? Epidemiology 1993; 4: Lees AW, Jenkins H i. May C L, Cherian G, Lam E W H, Hanson J. Risk factors and 10-year breast cancer survival in northern Alberta. Breast Cancer Res Treat 1989; 13: Albano W A, Recabaren J A, Lynch H T et al. Natural history of hereditary cancer of the breast and colon. Cancer 1982; 50: Kune G A, Kune S, Field B et al. Survival in patients with largebowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study. Dis Colon Rectum 1990; 33: Lothe R A, Peltomaki P, Meling G I el al. Genomic instability in colorectal cancer relationship to clinicopathological variables and family history. Cancer Res 1993; 53:

9 896 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 'Skolnick M. The Utah genealogical database: a resource for genetic epidemiology. In: Cflims J, Lyon J L, Skolnick M. Cancer Incidence in Defined Populations. US, Cold Spring Harbor Laboratory, ' Beam L L, Mineau G P, Anderton D L. Fertility Change on the American Frontier. Berkeley: University of California Press, Beahrs O H, Henson D E, Hutter R V P, Myers M H (eds). Manual for Staging of Cancer. Third Edn. Philadelphia: J B Lippincott Company, 1988, Ch. 11. " Kerber R. Statistical methods to calculate risk associated with family history. Genetic Epidemiology 1995 (In press). 12 Slattery M L, Kerber R A. Family history of cancer and colon cancer risk: The Utah Population Database. JNCI 1994; 86: BMDP Statistical Software. Berkeley: University of California Press, Slattery M L, Potter J D, Sorenson A W. Age and risk factors for colon cancer: are there implications for understanding differences in case-control and cohort studies? Cancer Causes Control 1994; 5: Potter J D, McMichael A J. Large bowel cancer in relation to reproductive and hormonal factors: a case-control study. JNCI 1983; 71: Potter J D, Slauery M L, Bostick R M, Gasptur S M. Colon cancer: A review of the epidemiology. Epidemiol Rev 1993; 15: (Revised version received April 1995)