A cohort study of cancer risk in relation to family histories of cancer in the Utah Population Database

BACKGROUND. it is well known that genetic variability affects the risk of many cancers, but details of the patterning of inherited cancer risk across different sites and age groups still are not well quantified. METHODS. The authors conducted a nested case-control study of the familial risk of 40 cancers based on a cohort of 662,515 individuals from the Utah Population Database. From 1 to 10 controls selected from the cohort were matched individually on gender, birth year, and birthplace to each cancer case; and familial standardized incidence ratios (FSIR) were calculated for both cases and controls. Conditional logistic regression was used to estimate relative risks and population-attributable risks (PARs) of cancer in relation to FSIR. Relative risks of cancer in first-degree through fifth-degree relatives of cases, compared with controls, were calculated using the proportional hazards methods. All analyses were adjusted for spouse affection status and Latter Day Saints church affiliation. RESULTS. Thirty-five of 40 cancers exhibited positive associations between risk and FSIR, and 21 of those associations were statistically significant. PAR estimates were strikingly high for prostate carcinoma (57%), breast carcinoma (39%), colon carcinoma (32%), lip carcinoma (31%), chronic lymphocytic leukemia (35%), and melanoma (32%). Both the proportion and the number of all cancers attributable to family history peaked at 32% in the group ages 65-84 years and remained high in the group age >= 85 years. CONCLUSIONS. A substantial portion of cancer risk was attributable to familial factors. The patterns of familial cancer recurrence among distant relatives suggested that simple genetic mechanisms may explain much of the familiality of cancer. (c) 2005 American Cancer Society.