Risk of cancer in first‐ and second‐degree relatives of testicular germ cell tumor cases and controls

Abstract

Risk factors for testicular germ cell tumors (TGCT) have not been well identified; however, data suggest that risks of cancer in family members of men with TGCT is elevated. Using family history data from 738 cases and 904 controls enrolled in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study from 2002 to 2005, the risk of cancer in first-and second-degree family members of these men was examined. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for reference age of case or control, race/ethnicity of case or control, sex of family member and lineage (maternal vs. paternal). An increased risk of all cancer among first-degree relatives of cases compared to controls was observed (RR 5 1.17, 95% CI: 1.01-1.35). There were suggestions of differences in risk when stratifying all relatives by lineage. For maternal relatives, there was a statistically significant increased risk of all cancer (RR 5 1.16, 95% CI: 1.04-1.30), digestive tract (RR 5 1.52, 95% CI: 1.15-2.00) and male genital organ cancer (RR 5 1.70, 95% CI: 1.15-2.51); there was also a suggestion of increased risks of hematopoetic cancers, cancers in the female genital organs and nonmelanoma skin cancer. For paternal relatives, there was a statistically significant association only with decreased risk of lung cancer (RR 5 0.69, 95% CI: 0.51-0.94). Thus, this study suggests that there may be aggregation of cancer among families of men diagnosed with TGCT. Published 2008 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.Key words: testicular cancer; family; aggregation Testicular germ cell tumors (TGCT) are the most common tumors among men in the U.S. aged 15-35 years, and the incidence of certain subtypes is still rising. 1 However, with the exception of cryptorchidism, which has been shown to increase risk substantially, other risk factors for TGCT have not been well identified, 2 although there is some evidence that a genetic predisposition to TGCT may exist. Several studies have shown that men with TGCT, compared to those without, are more likely to have a family member also affected with TGCT. Brothers of cases have been shown to have a 5-to 14-fold increase in risk of having TGCT, [3][4][5][6] and this elevated risk is particularly evident among twins. 7 Fathers of men with TGCT have also been shown to have elevated risk of having TGCT, although the increase in risk is not as high, ranging from 1.75 to 4.50. 3,4,6,[8][9][10] Other studies have indicated an elevated risk of other cancers among first-and second-degree family members, including a higher risk of breast cancer 8,9,11-14 and cancer in the female genital organs of mothers or sisters of TGCT cases. 9,11 Thus, it is reasonable to posit that there may be an increased risk of hormonally related cancers among family members of men with TGCT.There have been several studies on aggregation of cancer among families ide...

Cancer in first‐degree relatives and risk of testicular cancer in Denmark

“…Results from a Swedish study population similarly suggested a slightly increased risk of testicular cancer in association with familial NHL,10, 11 which to our knowledge is the only previous investigation of this association. Furthermore, we observed a borderline statistically significant association between familial esophageal cancer and testicular cancer, which is in agreement with prior studies 10, 17. A similar tendency was found in a previous Danish study of cases from an earlier time period, however statistically insignificant and based on very few cases 9.…”

“…Although an association, thus, has been established between the risk of testicular cancer and testicular cancer in first‐degree relatives, it is an open question whether an association also exists between risk of testicular cancer and nontesticular cancers in relatives. Such possible associations were explored in previous studies of which some indicated higher risk of testicular cancer in association with, among others, cancers of the pancreas, esophagus, genitals and breast as well as melanomas and lymphomas, whereas other studies did not find such associations 7–12, 16–19…”

Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

“…Genetic factors contribute significantly to TGCT susceptibility as exemplified by a 4- to 15-fold increased risk in the sons and brothers of affected men, respectively [8,9]. With conventional inheritance however, risk should be similar in sons and brothers.…”

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

“…Susceptibility to testicular germ cell tumors (TGCTs) is illustrative (2). Testicular cancer is the most common malignancy affecting young men (3), more than 90% of testicular cancers result from TGCTs (4), TGCTs rank third in heritability among all cancers (5), and family history is the strongest known risk factor with a two-to sixfold increase among sons and a 5-to 19-fold increase among brothers of affected individuals (6)(7)(8)(9). Despite the strong evidence for heritability, the only TGCT susceptibility factors identified in genome-wide association studies are the gr/gr deletion on the Y chromosome and autosomal variants in KITLG, SPRY4, BAK1, and DMRT1, which together account for less than 10% of risk (10)(11)(12)(13)(14).…”