Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family‐cancer database

Abstract

The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family-Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non-Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects.

Familial risk for gastric carcinoma: an updated study from Sweden

“…A Nordic twin study estimated that 62% variation in gastric cancer were owing to random environmental effects, 10% from shared environmental factors, and 28% from heritable effects (Lichtenstein et al, 2000); however, only the first figure was significant. Genetic and environmental components for gastric cancer have also been estimated based on the Swedish Family-Cancer Database (Czene et al, 2002). The results agreed with the twin study on the importance of random environmental effects (71%).…”

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

“…The three largest studies, based on the Swedish Family-Cancer Database (1)(2)(3), the Utah Population and Cancer Registry Database (4,5), and the Icelandic Cancer Registry (6), have shown familial aggregation for cancer at nearly every anatomical site. For common cancers such as prostate, breast, and lung, the familial relative risk (FRR), defined as the increase in risk associated with each affected first-degree relative of an individual, is generally estimated to be below or around 2.0.…”

“…For prostate cancer, the best-fitting estimate of the genetic correlation between aggressive and nonaggressive disease was at the upper boundary (ρ = 1, SE = 0.25), indicating a * Comparison of first-degree familial relative risk (95% CI) measured by our genome-wide association study (last column) with estimates of familial relative risk from the three largest family studies. Prior estimates are from (1,6,10), except for CLL (31), DLBCL (32), glioma (sibling) (33), pancreas (34), and esophagus (3). CI = confidence interval; CLL = chronic lymphocytic leukemia; DLBCL = diffuse large B-cell lymphoma; ER = estrogen receptor; FRR = family relative risk; GWAS = genome-wide association study.…”

Systematic review of the relationship between family history and lung cancer risk

“…Table 2 details the characteristics of the 17 cohort studies that have investigated the relationship between family history and lung cancer risk (Cannon-Albright et al, 1994;Goldgar et al, 1994;Hemminki et al, 1998Poole et al, 1999;Hemminki et al, 2001aHemminki et al, , b, 2004Dong and Hemminki, 2001;Czene et al, 2002;Li, 2002, 2003;Li and Hemminki, 2003Jonsson et al, 2004). In all, 13 of the studies (Cannon-Albright et al, 1994;Hemminki et al, 1998Hemminki et al, , 2001aHemminki et al, , b, 2004Dong and Hemminki, 2001;Czene et al, 2002;Li, 2002, 2003;Hemminki, 2003, 2004) were excluded from the metaanalysis as their data were replicated in subsequent studies. From the studies examining the Swedish Family Cancer Database, the study by Li and Hemminki (2005) was included in the pooled analysis as it examined the largest data set.…”