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      Familial risk in testicular cancer as a clue to a heritable and environmental aetiology

      research-article
      1 , 2 , 1 , *
      British Journal of Cancer
      Nature Publishing Group
      testicular cancer, seminoma, teratoma, familial risk, genetics, hereditary

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          Abstract

          The incidence of testicular cancer has increased in many countries, including Sweden, two- to four-fold over the last half a century, for unknown reasons (Bergstrom et al, 1996; Centre for Epidemiology, 2002). Of the two main types, seminomas and nonseminomas, the latter include teratomas with somatic differentiation and undifferentiated embryonal tumours (Kumar et al, 1997). However, some 60% of germ cell tumours of the testis contain multiple histological types and only 40% contain a single histological type (Kumar et al, 1997). The aetiology of testicular cancer remains largely unknown; some identified or suggested risk factors include undescended testis (cryptorchidism), a prior history of cancer in one testis (the opposite testis is at increased risk), in utero hormonal exposures, perinatal factors and family history of testicular cancer (Forman et al, 1992,1994; Heimdal et al, 1997; Moller and Skakkebaek, 1997; Swerdlow et al, 1997; Westergaard et al, 1998; Jacobsen et al, 2000; Hemminki and Mutanen, 2001). Compared to the relatively high incidence of testicular cancer in Sweden, first-generation immigrants generally show a decreased risk of testicular cancer compared to the natives, but this difference disappears in the next generation; this effect is marked among the sons of Finnish immigrants, whose risk is doubled compared to their fathers (Hemminki and Li, 2002b; Hemminki et al, 2002). Among the sons of the Danish immigrants, an equally large but opposite change takes place (Hemminki and Li, 2002a). In the present study, we have examined the genetic epidemiology of histology-specific testicular cancer in order to distinguish the contribution of heritable and environmental effects to etiology. Compared to the previous testicular cancer study from the Swedish Family-Cancer Database, an extended population and hence some 50% more familial testicular cancer cases are available (Dong et al, 2001), allowing analysis by age of onset through parental and fraternal probands. This, the largest cohort study of familial testicular cancer, offers new insight into the aetiology of the disease. SUBJECTS AND METHODS Statistics Sweden maintains a ‘Multigeneration Register’ in which offspring, born in Sweden in 1932 and later, are registered with their parents (as declared at birth) and they are organized as families (Hemminki et al, 2001a). Information on the Database is available at the Nature Genetics website as ‘Supplementary information’ (Hemminki and Granstrom, 2002). The data on families and cancers have a complete coverage, barring some groups of deceased offspring born in the 1930s and who died before 1991. Although this small group of offspring with missing links to parents has a negligible effect on the estimates of familial risk (Hemminki and Li, 2003), we limited the present study to offspring whose parents were known, to eliminate this possible source of bias. The ‘Multigeneration Register’ was linked using the individually unique national registration number to the Cancer Registry for the years 1958–2000. Cancer registration is considered now to be close to 100% complete (Centre for Epidemiology, 2002). The registered site of cancer is as a four-digit diagnostic code based on the 7th revision of the International Classification of Diseases (ICD-7). The following ICD-7 codes were grouped: ‘upper aerodigestive tract’ cancer codes 161 (larynx) and 140–148 (lip, mouth, pharynx), except for code 142 (salivary glands), ‘lymphoma’ codes 200, 202 (non-Hodgkin lymphoma), 201 (Hodgkin's disease) and ‘leukemia’ codes 204–207 (leukemias), 208 (polycytemia vera) and 209 (myelofibrosis). Rectal cancer, ICD-7 code 154, was subdivided into the anus (squamous cell carcinoma, 154.1) and mucosal rectum (154.0). Basal cell carcinoma of the skin is not registered in the Cancer Registry. Up to 1992, the histology of testicular cancers as in the Cancer Registry (WHO/HS/CANC/24.1 Histology Code) was used, to define seminoma (pathology codes 066) and teratoma (826, also including embryonal tumours). From 1993, ICD-O-2/ICD with histopathological data according to the Systematized Nomenclature of Medicine (SNOMED, http://snomed.org) was used, referred to here as ‘SNOMED’. Standardized incidence ratios (SIRs) were used to measure cancer risks for sons (i.e., offspring) according to the occurrence of cancers in their families. When more than two affected sons were found in any family, they were counted as independent events. Standardized incidence ratios were calculated for sons whose parents or brothers had the same, concordant cancer, that is, using parents or brothers as probands. Follow-up started for each offspring at birth, immigration or January 1, 1961, whichever came latest, and terminated on diagnosis of the first cancer, death, emigration, or the closing date of the study, December 31, 2000. Parents’ ages were not limited but sons were 0–68 years of age. All tumour incidence rates were based on the data in the Family-Cancer Database, and they were essentially similar to rates in the Swedish Cancer Registry. Rates were standardized to the European population. Standardized incidence ratios were calculated as the ratio of observed (O) to expected (E) number of cases. The expected numbers were calculated from 5-year-age-, sex-, tumour type-, period- (5-year bands), socioeconomic status- (six groups) and residential area- (three groups) specific standard incidence rates for all sons lacking a family history (Esteve et al, 1994). Confidence intervals (95% CI) were calculated assuming a Poisson distribution (Esteve et al, 1994). Risks for siblings were calculated using the cohort method, described elsewhere (Hemminki et al, 2001b). The kappa statistic was used as the measure of agreement between histologies: (observed number of cases−expected number of cases)/(1−expected number of cases) (Armitage and Berry, 1994). The kappa can assume values between −1 and 1; 0 shows a complete chance occurrence and −1 or 1 show a completely determined occurrence. Values between 0.40 and 0.60 are considered moderately determined occurrences. A negative kappa value would, in the present context, indicate a determined occurrence of a discordant histology, which is biologically unlikely, so we present only positive values of kappa in this paper. RESULTS The Family-Cancer Database, which covered years 1961–2000 from the Swedish Cancer Registry, included 4082 testicular cancers in sons of ages 0–68 years and 3878 fathers with testicular cancer (Table 1 Table 1 Numbers of cases of testicular cancer in sons and fathers   Son Father Histopathological type No. % Mean age Median age No. % Mean age Median age Pathology (1961–2000) Seminoma 2032 49.8 35.8 35 2293 59.1 41.1 39 Teratoma 1974 48.4 27.5 27 1483 38.2 33.1 33 Others 76 1.9 29.9 27 102 2.6 46.7 43 All 4082 100.0 31.7 31 3878 100 38.2 36                   SNOMED (1993–2000) Seminoma 871 56.4 37.7 36 673 66.2 42.0 39 Teratoma 385 25.0 28.8 27 193 19.0 35.6 33 Embryonal carcinoma 228 14.8 28.4 27 111 10.9 34.7 32 Others 59 3.8 28.5 28 40 3.9 42.6 37 All 1543 100.0 33.8 33 1017 100.0 40.0 37 ). Seminoma accounted for 49.8% and teratoma 48.4% in sons, while in fathers the proportions were 59.1 and 38.2%, respectively. Seminoma showed a 6–8-year later median age of onset than teratoma (35 vs 27 in offspring and 39–33 in fathers). According to the SNOMED histology, covering years 1993–2000, embryonal carcinoma accounted for 14.8% in sons and 10.9% in fathers. The age-specific incidence rates of testicular cancer among sons are shown in Figure 1 Figure 1 Age-specific incidence of testicular cancer in offspring according to the SNOMED histology in years 1993–2000. according to the SNOMED histology. The peak incidence for teratoma and embryonal carcinoma occurred at ages 20–24 years, and for seminoma showed a peak incidence at 30–34 years. Table 2 Table 2 SIR for histological type of testicular cancer in brothers by age difference     Brothers ages <5 years Brothers ages ⩾5years Histological types Age at diagnosis O SIR 95% CI O SIR 95% CI   Seminoma 0–24 1 11.49 0.00 65.89 0         >24 14 10.62 5.79 17.87 11 6.81 3.38 12.22   All 15 10.67 5.96 17.65 11 6.40 3.18 11.49                     Teratoma 0–24 5 11.61 3.66 27.31 5 10.74 3.39 25.26   >24 9 10.18 4.61 19.41 6 5.73 2.06 12.56   All 14 10.65 5.80 17.91 11 7.27 3.61 13.06                     All types 0–24 7 13.08 5.18 27.10 5 8.54 2.69 20.08   >24 23 10.27 6.50 15.44 17 6.29 3.66 10.09   All 30 10.81 7.29 15.45 22 6.69 4.19 10.15 Bold type: 95% CI does not include 1.00. O=observed; SIR=standardised incidence ratio; CI=confidence interval. presents risks for the histological types among brothers according to their age difference. Those born less than 5 years apart had higher risks, particularly at ages over 24 years, but below age 25 for the teratoma showed no age difference. Age- and histology-specific familial risk for testicular cancer was analysed using fathers or brothers as probands (Table 3 Table 3 SIR for histological types of testicular cancer in the offspring of paternal and fraternal probands     Seminoma Teratoma All types Histological types in proband Age at diagnosis O SIR 95% CI O SIR 95% CI O SIR 95% CI   Paternal proband Seminoma 0–24 0       3 4.62 0.87 13.69 3 3.78 0.71 11.18   >24 4 3.52 0.92 9.11 3 3.6 0.68 10.66 7 3.50 1.39 7.26   All 4 3.18 0.83 8.23 6 4.05 1.46 8.87 10 3.58 1.71 6.61                             Teratoma 0–24 0       3 8.64 1.63 25.58 3 7.2 1.36 21.32   >24 2 4.01 0.38 14.76 0       2 2.28 0.22 8.39   All 2 3.61 0.34 13.27 3 4.2 0.79 12.45 5 3.87 1.22 9.1                             All types 0–24 0       7 6.85 2.71 14.18 7 5.63 2.23 11.66   >24 6 3.53 1.27 7.73 3 2.42 0.46 7.15 9 3.02 1.37 5.75   All 6 3.19 1.15 6.98 10 4.42 2.1 8.15 16 3.78 2.16 6.16                             Fraternal proband Seminoma 0–24 1 11.7 0 67.04 3 7.79 1.47 23.07 5 10.29 3.25 24.22   >24 15 9.65 5.38 15.95 6 6.11 2.2 13.38 21 8.15 5.03 12.47   All 16 9.75 5.56 15.88 9 6.58 2.98 12.55 26 8.49 5.54 12.45                             Teratoma 0–24 0       7 14.35 5.69 29.74 7 11.53 4.57 23.89   >24 9 6.88 3.12 13.12 9 9.95 4.51 18.98 18 8.02 4.74 12.7   All 9 6.39 2.9 12.18 16 11.50 6.55 18.71 25 8.76 5.67 12.96                             All types 0–24 1 5.27 0 30.2 10 11.16 5.31 20.6 12 10.71 5.51 18.76   >24 25 8.52 5.51 12.59 15 7.77 4.33 12.84 40 8.1 5.78 11.03   All 26 8.32 5.43 12.21 25 8.84 5.72 13.07 52 8.58 6.41 11.26 Bold type: 95%CI does not include 1.00. O=observed, SIR=standardised incidence ratio; CI=confidence interval. ). The overall SIRs were approximately two-fold higher between brothers (8.58) than between sons and fathers (3.78). The risks were slightly higher for unmixed histologies compared to the mixed histologies for all significant SIRs. Among brothers, the SIR for concordant teratoma was 11.50, compared to 9.75 for seminoma. Concordant teratoma showed the highest SIR (14.35) among brothers aged 0–24 years. The proportion of sons with testicular cancer who had an affected father or brother was 1.67% (68 familial cases from Table 3 to 4082 cases from Table 1). Median ages of the familial cases did not differ from those of all cases (data not shown). Age-specific familial SIR for seminoma is shown in Figure 2A Figure 2 Age-specific SIR for histological type of testicular cancer in the offspring of paternal and fraternal probands: (A) seminoma; (B) teratoma. The numbers of cases are shown for each age group. * Shows that the 95% CI for the SIR did not include 1.00. for sons of fathers and among brothers with testicular cancer; Figure 2B shows the curves for teratoma. The shapes of the curves for teratoma resemble each other independent of proband status, with two peaks at 15–24 and 30–39 years. For seminoma, the peak SIR was observed at ages 40–44 years among brothers, and at 45–49 years among sons of affected fathers. We analysed using SNOMED histopathology, available only from 1993 (data not shown), that teratoma showed an age peak at 15–29 years in sons of fathers with testicular cancer (N=3, SIR=8.48, 95% CI 1.60–25.10). Among brothers, both SNOMED types showed peak SIRs at 30–44 years (seminoma, N=10, SIR=11.74, 95% CI 5.59–21.68; teratoma, N=5, SIR=26.16, 95% CI 6.26–61.55). No familial cases were found for embryonal carcinoma. Table 4 Table 4 SIR for testicular cancer in sons of parents and among siblings with cancer   Paternal Fraternal   Seminoma Teratoma Seminoma Teratoma Cancer sites O SIR 91% CI O SIR 95% CI O SIR 95% CI O SIR 95% CI Upper aerodigestive tract 15 0.83 0.46 1.37 17 1.19 0.69 1.19 2 0.84 0.08 3.11         Oesophagus 12 1.94 1.00 3.40 5 1.18 0.34 2.55 2 4.19 0.39 15.41         Stomach 34 0.99 0.68 1.38 18 0.77 0.45 1.21 1 0.59 0.00 3.36         Colorectuma 123 1.37 1.14 1.64 80 1.19 0.95 1.49 5 0.73 0.23 1.72 4 0.94 0.24 2.43 Liver 21 0.93 0.57 1.42 13 0.80 0.42 1.36 1 0.73 0.00 4.20         Pancreas 35 1.52 1.06 2.12 21 1.26 0.78 1.93 1 0.74 0.00 4.22 2 2.37 0.22 8.70 Lung 77 1.32 1.04 1.65 64 1.40 1.08 1.78 3 0.56 0.11 1.66 2 0.61 0.06 2.23 Breast 120 1.28 1.06 1.53 83 1.02 0.81 1.26 25 1.00 0.65 1.48 15 0.91 0.51 1.51 Cervix 14 0.79 0.43 1.33 17 1.14 0.66 1.83 5 0.99 0.31 2.33 1 0.26 0.00 1.50 Endometrium 24 1.12 0.72 1.67 16 0.95 0.54 1.54 4 1.30 0.34 3.36         Uterus, otherb 5 1.86 0.59 4.38 6 2.69 0.97 5.89                 Ovary 23 1.18 0.75 1.78 20 1.26 0.77 1.95 3 0.71 0.13 2.11         Prostate 113 1.04 0.85 1.25 81 1.01 0.80 1.25 3 0.63 0.12 1.86 2 0.78 0.07 2.87 Testis 6 3.27 1.18 7.17 10 4.50 2.15 8.32 26 8.46 5.52 12.41 25 8.95 5.79 13.23 Kidney 23 0.89 0.56 1.33 12 0.60 0.31 1.06 4 1.42 0.37 3.67 2 1.07 0.10 3.94 Urinary bladder 34 0.90 0.63 1.26 34 1.18 0.82 1.66 1 0.27 0.00 1.56 3 1.32 0.25 3.91 Melanoma 29 1.32 0.88 1.89 39 1.84 1.31 2.52 17 1.85 1.08 2.97 4 0.58 0.15 1.51 Skin, squamous cell 28 1.11 0.74 1.61 15 0.82 0.46 1.36 3 1.34 0.25 3.98 3 2.05 0.39 6.07 Nervous systemc 31 1.30 0.88 1.85 27 1.29 0.85 1.87 8 0.95 0.40 1.88 9 1.30 0.59 2.47 Thyroid gland 6 0.93 0.34 2.04 6 1.04 0.37 2.27 3 1.14 0.21 3.37 3 1.51 0.28 4.46 Endocrine glands 15 1.07 0.59 1.76 16 1.32 0.75 2.16 3 0.75 0.14 2.23 3 1.06 0.20 3.14 Connective tissue 5 0.99 0.31 2.32 4 0.94 0.24 2.43 3 2.26 0.43 6.70 2 1.86 0.18 6.84 Non-Hodgkin's lymphoma 35 1.56 1.08 2.17 22 1.19 0.75 1.81 3 0.65 0.12 1.92 6 1.85 0.66 4.04 Hodgkin's disease 9 2.40 1.09 4.58 0       2 1.03 0.10 3.79         Myeloma 12 1.04 0.54 1.83 8 0.93 0.40 1.85                 Leukaemia 25 1.18 0.76 1.74 19 1.16 0.69 1.81 3 0.78 0.15 2.31 1 0.30 0.00 1.73 All 874 1.19 1.11 1.27 653 1.13 1.04 1.22 131 1.19 0.99 1.41 87 1.13 0.91 1.40 Bold type: 95% CI does not include 1.00. O=observed; SIR=standardised incidence ratio; CI=confidence interval. a Three colorectal cancer-affected mothers had each two sons with testicular cancer, giving an SIR=7.49, 95% CI=1.41–22.18; of whom two pairs of bothers had seminoma, giving SIR=11.07 and 95% CI=1.04–40.71. b For all types of testicular cancer by mother's uterine cancer, SIR=2.40, 95% CI=1.23–4.20. c For all types of testicular cancer by father's nervous system cancer, SIR=1.50, 95% CI=1.03–2.10. presents associations of testicular cancer with other cancers in families, including mothers and sisters. Both seminoma (1.19) and teratoma (1.13) were increased when parents had any cancer (only associations at discordant sites being considered). For seminoma, a significantly increased risk was found when parents had colorectal, pancreatic, lung and breast cancer and non-Hodgkin's lymphoma and Hodgkin's disease. Seminoma was also increased when a sibling (brother or sister) had melanoma. Teratoma was associated with parental lung cancer and melanoma. For testicular cancer as a whole, an increased risk was found when the mother was diagnosed with ‘other uterine tumours’ or the father with nervous system cancer; these uterine tumours included three leiomyosarcomas, two adenocarcinomas, two chorioncarcinomas, two embryonal sarcomas, one stroma cell sarcoma and two unspecified sarcomas. It was also noteworthy that there were three mothers with colorectal cancer, each with two sons with testicular cancer (SIR=7.49, 95% CI=1.41–22.18), of whom two pairs of brothers had seminoma (SIR=11.07, 95% CI=1.04–40.71). The kappa test was applied to assess the histological concordance of testicular cancer (data not shown). The overall value was 0.01 between sons and fathers, and 0.26 among brothers; among brothers, the kappa value of seminoma was 0.23 and that of teratoma was 0.31. DISCUSSION The Swedish Family-Cancer Database contains national family data linked to the Swedish Cancer Registry. The inability to link some 10% of deceased offspring diagnosed with cancer to their parents (see Subjects and Methods) may cause small errors in the familial risks of fatal cancers. However, testicular cancer has had a good prognosis during the past decades. The missing links predominantly influence those born in the 1930s and who died before 1991, and we have not observed a difference in familial risks in comparing different diagnostic periods (Hemminki and Li, 2003). We conclude that this gap in parental links has no large effect on the present estimates. The markedly improved survival in testicular cancer may also be a source of bias, but adjustment for period should have minimized this. The many comparisons are relevant and, undoubtedly, some associations were due to chance; consistency within this study and with other studies, as well as biological plausibility, need assessing for causal inference. Familial occurrence of testicular cancer is well recognized but rare. The proportion of sons with testicular cancer who had an affected father or brother was 1.67% in the present study, consistent with previous studies, reporting affected first-degree relatives in 1.0–2.8% of cases (Heimdal et al, 1996; Westergaard et al, 1996; Dieckmann and Pichlmeier, 1997; Hemminki and Czene, 2002). Even the present overall familial risks of 3.78 (son–father) and 8.58 (brothers) were in line with the literature (Westergaard et al, 1996; Dieckmann and Pichlmeier, 1997; Heimdal et al, 1997; Dong et al, 2001). The SNOMED data, covering cases diagnosed between 1993 and 2000, showed an even larger difference between the two proband groups, 3.12 (son–father) and 9.62 (brothers), respectively. There was no large difference in familial risks between seminomas and teratomas among father–son pairs. However, there appeared to be a large difference in the familial risk between the pure and mixed histological types among brothers. The risks ranged from 12 (teratoma–teratoma) and 10 (seminoma–seminoma) for pure histologies to six for mixed histologies. Consistent with these findings, the kappa test was 0.01 between sons and fathers, whereas between brothers seminoma showed a value of 0.23 and teratoma a value of 0.31. These are still low values, but the interpretation is difficult because of the relatively small number of cases. The lower kappa values between sons and fathers than between brothers may be due to a more defined disease phenotype within one generation than between two generations. The higher familial risk for testicular cancer among brothers than father–son pairs may suggest the involvement of a recessive mode of inheritance or an X-linked susceptibility locus in the aetiology of testicular cancer, consistent with the segregation analysis and the gene-mapping findings (Heimdal et al, 1997; Rapley et al, 2000). Such results would point to the importance of the maternal lineage of inheritance and perhaps also maternally exerted environmental factors. The difference in SIR among brothers close in age (10.81) compared to those further apart (6.69) suggests environmental effects. Testicular cancer has been reported as the site with the highest proportion of childhood-shared environmental effects in a family study of all major cancers (Czene et al, 2002). Although both histological types showed the effect of age difference, the risks for early-onset teratoma appeared to be least influenced by the age difference. These results suggest that environmental factors during childhood and adolescence influence the risk of contracting a late-onset testicular cancer (Hemminki et al, 2002; Hemminki and Li, 2002b). Identifying these factors might explain the riddle of increasing incidence trends and also the difference between immigrants and their sons (Hemminki and Li, 2002a). On the other hand, the search for heritable effects should target brother pairs with an early-onset teratoma. Age-specific familial risks of Figure 2 showed the highest risks for seminoma in the 40 s, for both brothers and son–father pairs. For teratoma, two discrete peaks were noted, particularly among brothers. The early-onset teratoma peak (20–24 years) coincided with its peak incidence, but the late-onset peak (35–39 years) occurred 15 years later and close to the peak fraternal risk of seminoma. Based on the risks by age difference, the younger teratoma component may be the most heritable familial component, whereas the later component of teratoma and seminoma may have a strong environmental origin. In families of seminoma patients, associations were found with colorectal, pancreatic, lung and breast cancer and non-Hodgkin's lymphoma and Hodgkin's disease among parents. Among brothers, there was an association with seminoma and melanoma. Teratoma was associated with parental lung cancer and melanoma. However, no association has been found for primary melanoma or lung cancer following first testicular cancer (Dong et al, 2001). Testicular cancer was associated with mothers’ unusual uterine tumours, including chorionepithelioma (SIR=2.40, 95% CI 1.23–4.20). No oestrogen-related cancer risks were observed in mothers of testicular cancer patients in a Danish study (Kroman et al, 1996). In the 26 families in our study with two sons with testicular cancer, three had mothers with colorectal cancer (SIR=7.49, 95% CI=1.41–22.18), of whom two pairs of brothers had seminoma (SIR=11.07, 95% CI=1.04–40.71), but none had a father with testicular cancer. However, there is no previous evidence of an association between testicular and colorectal cancers, but multiple testing may have resulted in associations due to chance. In summary, the present study may offer some explanation to the inability in finding susceptibility genes for testicular cancer. The high familial risk may be the product of shared childhood environment and heritable causes and so may be difficult to untangle. Identifying any relevant environmental factors will be challenging but may explain some of the changes in testicular cancer incidence. For gene identification, fraternal pairs with teratoma below age 25 may be particularly useful.

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          • Record: found
          • Abstract: found
          • Article: not found

          Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database.

          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. Copyright 2002 Wiley-Liss, Inc.
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            • Record: found
            • Abstract: found
            • Article: not found

            Risk of testicular cancer in men with abnormal semen characteristics: cohort study.

            To explore the associations between semen characteristics and subsequent risk of testicular cancer. Cohort study. 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. Standardised incidence ratios of testicular cancer compared with total population of Danish men. Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was "peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.
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              • Record: found
              • Abstract: found
              • Article: not found

              Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon.

              For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development can be traced back to the first half of this century. By evaluating data from six countries with long periods of cancer registration (Denmark, Norway, Sweden, the former German Democratic Republic [East Germany], Finland, and Poland), we sought to determine whether the increase in testicular cancer risk follows a birth cohort pattern and, if so, to quantify and compare any birth cohort effects. A total of 30,908 incident cases of testicular cancer, diagnosed from 1945 through 1989 in men who were 20-84 years of age, were identified in population-based cancer registries in the six countries. In addition to performing simple trend analyses, we fitted several Poisson regression models (with the explanatory variables age, time period [calendar time], and birth cohort) to the data. Individual models were estimated by the maximum likelihood method. The age-standardized incidence of testicular cancer was found to vary among the six populations and, on the basis of total registration data, increased annually at rates ranging from 2.3% (in Sweden) to 5.2% (in East Germany). A comparison of several regression models indicated that birth cohort was a stronger determinant of testicular cancer risk than was calendar time for all six populations. Within each population, little variation in testicular cancer risk was observed for men born between 1880 and 1920; thereafter, the risk began to increase. Among men born in Denmark, Norway, and Sweden between 1930 and 1945 (the period encompassing the Second World War), the increasing trend in risk was interrupted (i.e., a leveling in risk occurred). After 1945, an uninterrupted increase in risk was observed for all six populations. With men born around 1905 as the reference group, the relative risk of testicular cancer for those born around 1965 varied from 3.9 (95% confidence interval [CI] = 2.7-5.6) in Sweden to 11.4 (95% CI = 8.3-15.5) in East Germany. The increasing trend in testicular cancer risk observed for these six populations follows a birth cohort pattern. This distinct risk pattern provides a framework for the identification of specific etiologic factors.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                16 March 2004
                27 April 2004
                04 May 2004
                : 90
                : 9
                : 1765-1770
                Affiliations
                [1 ] 1Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden
                [2 ] 2Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
                Author notes
                [* ]Author for correspondence: xinjun.li@ 123456cnt.ki.se
                Article
                6601714
                10.1038/sj.bjc.6601714
                2410275
                15208620
                48f4eafe-a664-4733-9254-a54f47c8b2eb
                Copyright 2004, Cancer Research UK
                History
                : 24 October 2003
                : 09 January 2004
                : 19 January 2004
                Categories
                Epidemiology

                Oncology & Radiotherapy
                testicular cancer,seminoma,genetics,teratoma,hereditary,familial risk
                Oncology & Radiotherapy
                testicular cancer, seminoma, genetics, teratoma, hereditary, familial risk

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