Epidemiological Studies

Four case-control and three cohort studies have systematically examined the risk of CLL and other LPDs in relatives of patients. Table 1 summarizes the characteristics of each of the studies and the estimates of the familial risks obtained. All the studies found that risk of leukemia or lymphocytic leukemia was elevated in relatives. The study reported by Gunz et al. in 1975 (1) was based on a survey of 909 families ascertained through leukemia cases. Giles et al. (2) made no distinction between types of LPD in their analysis of the family histories of cases diagnosed between 1972 and 1980 in Tasmania. In 1994, Goldgar et al. (3) systematically analyzed the clustering of malignancy at 28 distinct sites using the Utah population database. Relatives of lymphocytic leukemia cases were at a sixfold increased risk of the same hematological malignancy. The risk of LPD in relatives reported in the three cohort studies was comparable to that observed in the four case-control studies. Although none of these studies has systematically estimated familial risks by specific leukemia type, it is likely that the familial risk reflects an increased risk of CLL since acute lymphoblastic leukemia—the primary potential confounding diagnosis—does not display an increased sibling risk (4).

A number of inherited susceptibility genes cause cancer at several sites. Therefore any excess of cancer at sites other than CLL in relatives may reflect in part the pleiotropic effects of an

From: Contemporary Hematology Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management Edited by: G. B. Faguet © Humana Press Inc., Totowa, NJ 389

Table 1

Familial Risks of CLL and other LPDs

Table 1

Familial Risks of CLL and other LPDs

Observed

Expected

Risk (%)

Study

Diagnosis in index case

Relative

(no.)

(no.)

(95% CI)

Cohort studies

Giles et al. (2)

LPD

LPD in first-degree relatives

35

10.3

3.4 (2.4-4.7)

Gunz et al. (1)

Leukemia

Leukemia in first-degree relatives

16

6.61

2.4 (1.9-3.9)

Goldgar et al. (3)

Lymphocytic leukemia

Lymphocytic leukemia in first-degree relatives

18

3.6

5.7 (2.6-10.0)

Case-control studies

Cartwright et al. (45)

CLL

Lymphocytic leukemia in blood relatives

5/330

2/559

4.3 (0.9-19.5)

Linet et al. (46)

CLL

Leukemia in parents and siblings

25/342

10/342

2.6 (1.2-5.5)

Pottern et al. (47)

CLL

Leukemia in parents and siblings

13/237

30/1207

2.3 (1.2-4.4)

Radovanovic et al. (48)

CLL

Leukemia in first- and second-degree relatives

7/130

0/130

Fig. 1. Chronic lymphocytic leukemia (CLL) in one family. CLL was not recorded in the first two generations, which is consistent with incomplete penetrance. Solid symbols, diagnosis of CLL. (Adapted from ref. 59.)
Fig. 2. Chronic lymphocytic leukemia recorded in one family. (Adapted from ref. 54.)

inherited predisposition gene. In addition to a possible relationship between CLL and other B-cell LPDs, a relationship between lymphocytic leukemia and granulocytic leukemia and rectal cancer was observed in the study reported by Goldgar et al. (3).

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