Original Article
Cancer in the Parents of Children with Cancer
N Engl J Med 1995; 333:1594-1599December 14, 1995
- Abstract
Background
Certain types of cancer in children and young adults have been linked with an increased risk of cancer in close relatives. However, the relation between childhood cancer and familial risk remains to be fully assessed in population-based studies.
Methods
We conducted a nationwide study in Denmark of 11,380 parents of children with cancer. The children were identified from records in the Danish Cancer Registry; their parents were identified from population registers. The occurrence and rate of cancer in the parents were determined with use of the Cancer Registry's files and compared with national incidence rates for various categories of tumor.
Results
Overall, 1445 cancers were diagnosed in the parents, as compared with 1496 expected from national incidence rates, to yield standardized incidence ratios of 1.0 (95 percent confidence interval, 0.9 to 1.0) for all parents, 1.0 for mothers, and 0.9 for fathers. The lower rate of cancer among fathers reflected their lower standardized incidence ratio for lung cancer (0.8; 95 percent confidence interval, 0.6 to 0.9), as calculated from 114 observations.
Conclusions
Genetic determinants are important in several types of childhood cancer, but the genetic susceptibility to tumors does not generally extend to the parents of children with cancer, nor do the patterns of incidence point to the influence of shared environmental factors. Thus, cancer in children should not be viewed as a general marker for an increased risk of cancer in the patients' parents.
Media in This Article
Table 1
Characteristics of the 5863 Children with Cancer.Table 2
Standardized Incidence Ratios for Cancer in the Parents of 5863 Children with Cancer.Article Activity
- Article
Neoplasia in early life has characteristics that suggest the importance of heritable factors in the causation of cancer.1 Clinical and epidemiologic surveys2-10 have revealed that close relatives of children with cancer have an overall rate of cancer7-10 and rates of certain types of cancer2-6 that are higher than those in the general population. This finding implies that the occurrence of cancer in a child can predict an increased risk of cancer in the child's parents or other relatives. An inherited susceptibility to tumors has been well documented for bilateral retinoblastoma1 and for Li–Fraumeni syndrome, in which families are prone to breast cancer and neoplasms of early life, such as childhood sarcoma.11 These two hereditary disorders have been linked to germ-line mutations of the tumor-suppressor genes RB1 and p53, respectively. It has been suggested that the mothers of children with sarcoma should be screened for breast cancer in early adulthood.12,13 However, whether the occurrence of childhood cancer can predict an increased familial risk of cancer has heretofore not been assessed in large, population-based studies.
Methods
In this nationwide study in Denmark, covering a period of almost 50 years, the incidence of various types of cancer was measured in large cohorts of the parents of patients with childhood cancer and then compared with the rates of cancer in the general population.
Study Population
In Denmark, during the period 1943 to 1985, 5917 children under 15 years of age were given a diagnosis of some type of cancer, including tumors of the brain. We identified the children through the files of the Danish Cancer Registry, which in each case provided information on the tumor, the name and sex of the child, and the child's date of birth.14 For children alive on April 1, 1968, when the Central Population Register was established, and children born after that date, a unique personal identification number was also available. Only children born in Denmark were included in the study; this led to the exclusion of 17 children (0.3 percent) who were born elsewhere. The emigration of persons born in Denmark has been negligible since the early 1960s, never exceeding 0.5 percent per year.15
Cases of childhood cancer reported during the period 1943 to 1977 were reevaluated on the basis of the initial information given by the clinicians and pathologists,16 so that all cases occurring between 1943 and 1985 could be classified according to the system set forth in the International Classification of Diseases for Oncology. 17 In our analyses, we used a defined set of diagnostic categories (Table 1Table 1
Characteristics of the 5863 Children with Cancer.) formed by aggregating groups of codes, as proposed by the International Agency for Research on Cancer in an international study of childhood cancer.18 The parents of children with cancer were traced in one of two ways. With the personal identification numbers of the children with cancer who were alive on April 1, 1968 (or who were born later) as the key identifiers, the name, identification number, and date of death or emigration (if applicable) of the parents of each child were determined by computerized records linkage. For families in which the child with cancer or a parent had died before April 1, 1968, information about the parents had to be obtained manually from the local population registers of the municipalities in which the families had lived at the time of the diagnosis of cancer. Parents in this latter group were then traced by computer in the Central Population Register or traced manually in the Death Certificate File at the National Board of Health, to verify personal data and dates of death or emigration. More details of the tracing procedures have been described elsewhere.19 A total of 37 adopted children with cancer (0.6 percent) were excluded from the study, leaving a total of 5863 children with cancer in the study group (Table 1).
Identifying Cancer in the Parents
We linked data on the parents with data in the Danish Cancer Registry, using the parents' personal identification numbers or, if they had died before April 1, 1968, their dates of birth, dates of death, and names. The period of follow-up for the occurrence of cancer among parents of a child with cancer extended from the date of birth of the child (or from January 1, 1943, when the registry began, for children born before that date) to the date of the parent's death or emigration, or until December 31, 1989, whichever came first. Cancers in the parents, including benign tumors of the brain and papillomas of the urinary tract, were classified according to the modified Danish version of the International Classification of Diseases, 7th Revision (ICD-7).20 National incidence rates for these categories of tumor, calculated according to sex, age (in five-year groups), and five-year historical periods were applied to the person-years of observation in the parental cohorts to obtain the number of cancers expected in the parents if they had the same rates of incidence as the general population.
Statistical Analysis
The statistical methods were chosen on the basis of the assumption that the observed number of cases of cancer in any specific category follows a Poisson distribution. Tests of significance and confidence intervals for the standardized incidence ratio — the ratio of the observed to the expected number of cancers — were calculated with use of the Miettinen exact confidence limits if the observed number of cases was small; otherwise, an accurate asymptotic approximation was used.21 Separate analyses were performed for a number of diagnostic categories of childhood cancer. Account was also taken of the age of the child and the parent at the time of the diagnosis of cancer.
Results
Table 1 shows characteristics of the children with cancer. Of the parents of the 5863 children, 5747 mothers (98.4 percent) and 5633 fathers (96.5 percent) were successfully traced (23 pairs of parents had 2 children with cancer, and 1 pair had 3). On average, each parent was at risk for cancer for 28 years (range, 3 months to 47 years), beginning at the date of birth of the index child; 2364 parents (21 percent) died and 112 (1 percent) emigrated during follow-up. By the end of the study period, 320,000 person-years of parents' exposure to risk had been observed. Overall, 1445 cancers were diagnosed, and 1496 were expected (Table 2Table 2
Standardized Incidence Ratios for Cancer in the Parents of 5863 Children with Cancer.), which yielded a standardized incidence ratio of 1.0 (95 percent confidence interval, 0.9 to 1.0). The standardized incidence ratio was 1.0 (95 percent confidence interval, 0.9 to 1.1) for mothers and 0.9 (95 percent confidence interval, 0.9 to 1.0) for fathers. The slightly lower overall ratio for fathers was due to their standardized incidence ratio for lung cancer (0.8, significantly lower than the overall ratio in all parents), calculated on the basis of 114 observed cases, and their ratios for prostatic cancer (0.9) and testicular cancer (0.7). No similarly lower rate of lung cancer was seen in mothers (50 cases observed vs. 43.8 expected).Table 3Table 3
Standardized Incidence Ratios for Cancer in the Parents of 580 Children with Osteogenic or Soft-Tissue Sarcomas. shows the patterns of cancer among 1135 parents of 580 children with osteogenic or soft-tissue sarcomas, the childhood tumors most consistently associated with an increased risk of cancer in parents. Overall, 177 cancers were reported, and 188.3 were expected (standardized incidence ratio, 0.9); 93 were reported in mothers (standardized incidence ratio, 1.1) and 84 in fathers (standardized incidence ratio, 0.8). With the exception of lung cancer in fathers, which occurred at a 54 percent lower rate than expected (9 cases observed vs. 19.8 expected), and a slightly elevated risk of multiple myeloma in mothers, no meaningful deviation from the expected figures was seen in parents for any of the categories of cancer (Table 3). Specifically, the observation of 20 breast cancers in mothers was close to the 20.3 cases expected, although if the risk of breast cancer is analyzed only for mothers of children given a diagnosis of sarcoma before the age of three, a significant, threefold increase in risk is seen on the basis of 9 observed cases (Table 4Table 4
Standardized Incidence Ratios for Breast Cancer in Mothers of Children with Osteogenic or Soft-Tissue Sarcomas, According to the Age of the Child at Diagnosis and the Age of the Mother.). The association with breast cancer was particularly strong for mothers under 45 years of age (standardized incidence ratio, 5.4).There was a tendency for most forms of cancer in children under the age of 3 to be associated to some extent with breast cancer in mothers under the age of 45, with a significantly increased incidence ratio for such women, for all cancers combined, of 1.9 (21 observed cancers vs. 11.0 expected). These findings suggest that the excess of 10 cases of breast cancer in mothers under the age of 45 was related to the occurrence of cancer in their offspring; the 10 cases represent 6 percent of the 168 cases of breast cancers observed in the study and 22 percent of the 45 breast cancers in mothers under the age of 45. A total of 17 cases of breast cancer in mothers were observed in association with childhood cancers other than sarcomas, whereas 10.3 were expected, for a standardized incidence ratio of 1.7 (95 percent confidence interval, 1.0 to 2.6). Cancers of other types occurred in mothers at the expected rates (28 observed vs. 27.9 expected).
Table 5Table 5
Standardized Incidence Ratios for All Cancers Combined and Cancers at Selected Sites in the Parents of 5155 Children with Cancers Other Than Osteogenic and Soft-Tissue Sarcomas. shows the standardized incidence ratios for all types of cancer combined in the mothers and fathers of children with cancers other than sarcomas. The overall risk of cancer was slightly lower in the parents of children with leukemia and was significantly lower in the fathers of children with renal tumors (mainly Wilms' tumor); the latter finding was based on 33 observed cases and 49.5 expected cases (standardized incidence ratio, 0.7) and was not explained by a lower number of any particular type of cancer in the fathers. Also included in Table 5 are the few significant relations — each derived from at least three observations — between a particular type of childhood cancer and the type of cancer, if any, that developed in parents. The most striking of these are the relations between childhood leukemia and kidney cancer in mothers (standardized incidence ratio, 2.1) and, to a lesser extent, fathers (standardized incidence ratio, 1.4), and those between non-Hodgkin's lymphoma in children and cancers of the brain (standardized incidence ratio, 2.9) and uterine cervix (standardized incidence ratio, 2.0) in mothers. A positive association between cancers of the same type was identified only for childhood tumors of the central nervous system, which were associated with a slight excess of central nervous system tumors in both mothers (standardized incidence ratio, 1.2) and fathers (standardized incidence ratio, 1.3).To evaluate whether some characteristics of the distribution of childhood cancer might be especially predictive of parental risk, we examined 24 families in which more than one child had cancer and 54 families in which a child with cancer eventually had a second primary tumor. The overall standardized incidence ratio for cancer in the parents of the first group was 1.0 (95 percent confidence interval, 0.3 to 2.4), calculated on the basis of 5 cases of cancer in parents, and in the parents of the second group, 0.9 (95 percent confidence interval, 0.5 to 1.5), calculated on the basis of 16 cases.
Discussion
Our main finding is that the overall occurrence of cancer in the parents of children with cancer, 1445 observed cases, was remarkably close to that expected from incidence rates in the general adult population. The parents' risk of cancer was not increased by having a child with any of the 10 major categories of disease, including osteogenic and soft-tissue sarcomas (of which there were 580 cases). These findings conflict with those of some earlier studies, which found that first-degree relatives of children with cancer, especially sarcomas, had an overall increased risk of cancer.7-10 The earlier studies involved 177 children with soft-tissue sarcomas (1.7 times the average risk of cancer was found in mothers)7; 159 children with soft-tissue sarcomas (1.3 times the average risk of cancer was found in first-degree relatives)9; 47 cases of bilateral retinoblastoma (1.3 times the average risk of cancer was found in first-degree relatives)8; and 326 children with a variety of types of cancer (1.7 times the average risk of cancer was found in mothers).10 Our findings are more in line with hospital-based studies in Italy,22 the United States,13 and France,23 which reported no overall increased risk of cancer in the first-degree relatives of 195 children with soft-tissue sarcomas, 88 children with sarcomas of the bone and soft tissue, and 501 children with Wilms' tumor, respectively.
We have no reason to believe that our failure to find a general link between the occurrence of cancer in children and that in their parents is due to bias in our study. The Danish Cancer Registry records data from the country's entire population, so practically all cases of childhood cancer occurring after 1943 were identified, as were more than 97 percent of the parents of the children involved; this minimizes the possibility of bias due to the selection of study subjects. Similarly, very few persons born in Denmark emigrate to other countries. Information bias is also unlikely; the study groups were established and parenthood determined before files were searched for evidence of cancer in the parents, and the study relied on population registers that are kept for administrative purposes.
We saw a few noteworthy relations between childhood cancer and specific types of cancer in parents, including an increase in breast cancer in mothers under the age of 45 whose children had been given a diagnosis of cancer before the age of 3. This link was based on an excess of 10 breast cancers (about 20 percent) among the 45 observed in mothers under the age of 45, which suggests that cancer in young children (that diagnosed before the age of 3) is a useful predictor of breast cancer in relatively young mothers. The strength of the association may be somewhat underestimated, because the national rates for breast cancer that we used are influenced by an approximately 30 percent higher risk of breast cancer among nulliparous women than among parous women.24 Since any group of mothers would therefore be likely to have a lower risk of breast cancer than the group of all women in the country, the standardized incidence ratio is an underestimate. On the other hand, the large-scale, quantitative importance of familial susceptibility seems limited, since the 10 cases of breast cancer predicted by the occurrence of cancer in young children make up only about 0.1 percent of the 11,911 cases of breast cancer that were diagnosed during the study period in Danish women under the age of 45.
The association with breast cancer was particularly strong for mothers of children with sarcoma diagnosed before the age of 3. This finding is in accordance with the familial syndrome of soft-tissue sarcomas, breast cancer, and other neoplasms in young adults and children initially described by Li and Fraumeni in 196911 and confirmed by longitudinal studies of high-risk families25,26 and by a British population-based study that found the risk of breast cancer in the mothers of children with soft-tissue sarcoma to be three times the average for the population at large.6,7 Susceptibility to breast cancer also occurs in the families of children with osteosarcoma and chondrosarcoma,26 as indicated both by our study and by another population-based study from England.3
The substantially lower risk of lung cancer that we found in the fathers of children with cancer has not been reported previously and was not paralleled by a lower risk among mothers. Although fathers may have changed their smoking habits after cancer developed in their children, this seems an insufficient explanation for the effect, since even former smokers are prone to have lung cancer. Because genetic factors also seem unlikely to play a part, the finding may be a matter of chance. Our general finding that the risk of lung cancer is not elevated in the parents of children with cancer is consistent with recent studies that have shown no relation between parental smoking habits and childhood neoplasms.27,28
In our study, the overall risk of cancer was also significantly lower than expected in the fathers of children with Wilms' tumor; no particular risk pattern according to the father's type of cancer was seen, and no similar effect was noticed in mothers. We have no plausible explanation for this finding other than its being a result of multiple statistical testing; we tested 22 types of cancer in parents, both men and women, against each of 11 diagnostic groups of childhood cancer. Given 484 such comparisons and our practice of establishing significance with 95 percent confidence intervals, chance alone might result in 24 “significant” findings. We in fact observed 11 positive and 7 negative associations that had statistical significance.
Aside from those already mentioned, our study revealed few associations between cancer in children and cancer in their parents. The increased risk of kidney cancer observed in mothers and fathers of children with leukemia, irrespective of the child's age at diagnosis, calls for further studies of shared risk factors, as does the increased risk of cervical cancer observed in the mothers of children with non-Hodgkin's lymphoma. The slight elevation of the risk of brain tumors in the mothers of children with lymphoma, although based on few observations, is consistent with previous reports of familial tumor complexes.29 The high risk of melanoma among fathers of children with retinoblastoma is an intriguing finding, given that children with heritable retinoblastoma are prone to have melanoma as a second tumor30 (however, the finding in our study occurred in children with unilateral disease19). A link between melanoma and retinoblastoma has also been noted in case reports,31 as well as an accompanying association with the dysplastic nevus syndrome.32 Except for the link between sarcoma in children and early-onset breast cancer in their mothers, which has been previously reported, the associations in our study must be interpreted with caution because of the increased effects of chance in multiple comparisons.
Supported by grants from the Danish Cancer Society, the Danish Medical Research Council, and the National Institutes of Health.
Source Information
From the Division for Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (J.H.O., N.S., A.B.); and the Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md. (J.D.B., J.F.F.).
Address reprint requests to Dr. Olsen at the Danish Cancer Society, Division for Cancer Epidemiology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
- References
References
1
Knudson AG Jr . Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 1985;45:1437-1443
Web of Science | Medline2
Farwell J ,Flannery JT . Cancer in relatives of children with central-nervous-system neoplasms. N Engl J Med 1984;311:749-753
Full Text | Web of Science | Medline3
Hartley AL ,Birch JM ,Marsden HB ,Harris M . Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma. Br J Cancer 1986;54:819-823
CrossRef | Web of Science | Medline4
Li FP ,Fraumeni JF Jr ,Mulvihill JJ , et al. A cancer family syndrome in twenty-four kindreds. Cancer Res 1988;48:5358-5362
Web of Science | Medline5
DerKinderen DJ ,Koten JW ,Nagelkerke NJD ,Tan KEWP ,Beemer FA ,Den Otter W . Non-ocular cancer in patients with hereditary retinoblastoma and their relatives. Int J Cancer 1988;41:499-504
CrossRef | Web of Science | Medline6
Birch JM ,Hartley AL ,Marsden HB ,Harris M ,Swindell R . Excess risk of breast cancer in the mothers of children with soft tissue sarcomas. Br J Cancer 1984;49:325-331
CrossRef | Web of Science | Medline7
Birch JM ,Hartley AL ,Blair V , et al. Cancer in the families of children with soft tissue sarcoma. Cancer 1990;66:2239-2248
CrossRef | Web of Science | Medline8
Strong LC ,Herson J ,Haas C , et al. Cancer mortality in relatives of retinoblastoma patients. J Natl Cancer Inst 1984;73:303-311
Web of Science | Medline9
Strong LC ,Stine M ,Norsted TL . Cancer in survivors of childhood soft tissue sarcoma and their relatives. J Natl Cancer Inst 1987;79:1213-1220
Web of Science | Medline10
Thompson EN ,Dallimore NS ,Brook DL . Parental cancer in an unselected cohort of children with cancer referred to a single centre. Br J Cancer 1988;57:127-129
CrossRef | Web of Science | Medline11
Li FP ,Fraumeni JF Jr . Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome? Ann Intern Med 1969;71:747-752
Web of Science | Medline12
Hartley AL ,Birch JM ,Blair V ,Kelsey AM ,Harris M ,Jones PHM . Patterns of cancer in the families of children with soft tissue sarcoma. Cancer 1993;72:923-930
CrossRef | Web of Science | Medline13
Burke E ,Li FP ,Janov AJ ,Batter S ,Grier H ,Goorin A . Cancer in relatives of survivors of childhood sarcoma. Cancer 1991;67:1467-1469
CrossRef | Web of Science | Medline14
Jensen OM, Storm HH, Jensen HS. Cancer registration in Denmark and the study of multiple primary cancers, 1943–80. In: Greenwald P, ed. Multiple primary cancers in Connecticut and Denmark. National Cancer Institute monograph 68. Washington, D.C.: Government Printing Office, 1985:245-51. (NIH publication no. 85-2714.)
15
Matthiessen PC. Growth of the population: causes and consequences. Copenhagen, Denmark: Munksgaard, 1984. (In Danish.)
16
de Nully Brown P ,Hertz H ,Olsen JH ,Yssing M ,Scheibel E ,Jensen OM . Incidence of childhood cancer in Denmark 1943-1984. Int J Epidemiol 1989;18:546-555
CrossRef | Web of Science | Medline17
International classification of diseases for oncology. Geneva: World Health Organization, 1976.
18
Birch JM ,Marsden HB . A classification scheme for childhood cancer. Int J Cancer 1987;40:620-624
CrossRef | Web of Science | Medline19
Olsen JH ,Winther JH ,Brown PN . Risk of nonocular cancer in first-degree relatives of retinoblastoma patients. Hum Genet 1990;85:283-287
CrossRef | Web of Science | Medline20
Manual of the international statistical classification of diseases, injuries, and causes of death. 7th rev. Geneva: World Health Organization, 1957.
21
Rothman KJ, Boice JD Jr. Epidemiologic analysis with a programmable calculator. Washington, D.C.: Government Printing Office, 1979. (DHHS publication no. (NIH) 79-1649.)
22
Pastore G ,Mosso ML ,Carli M , et al. Cancer mortality among relatives of children with soft-tissue sarcoma: a national survey in Italy. Cancer Lett 1987;37:17-24
CrossRef | Web of Science | Medline23
Moutou C ,Hochez J ,Chompret A , et al. The French Wilms' tumour study: no clear evidence for cancer prone families. J Med Genet 1994;31:429-434
CrossRef | Web of Science | Medline24
Ewertz M ,Duffy SW ,Adami H-O , et al. Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries. Int J Cancer 1990;46:597-603
CrossRef | Web of Science | Medline25
Li FP ,Fraumeni JF Jr . Prospective study of a family cancer syndrome. JAMA 1982;247:2692-2694
CrossRef | Web of Science | Medline26
Garber JE ,Goldstein AM ,Kantor AF ,Dreyfus MG ,Fraumeni JF Jr ,Li FP . Follow-up study of twenty-four families with Li-Fraumeni syndrome. Cancer Res 1991;51:6094-6097
Web of Science | Medline27
Pershagen G ,Ericson A ,Otterblad-Olausson P . Maternal smoking in pregnancy: does it increase the risk of childhood cancer? Int J Epidemiol 1992;21:1-5
CrossRef | Web of Science | Medline28
Severson RK ,Buckley JD ,Woods WG ,Benjamin D ,Robison LL . Cigarette smoking and alcohol consumption by parents of children with acute myeloid leukemia: an analysis within morphological subgroups -- a report from the Childrens Cancer Group. Cancer Epidemiol Biomarkers Prev 1993;2:433-439
Web of Science | Medline29
Grundy GW ,Creagan ET ,Fraumeni JF Jr . Non-Hodgkin's lymphoma in childhood: epidemiologic features. J Natl Cancer Inst 1973;51:767-776
Web of Science | Medline30
Eng C ,Li FP ,Abramson DH , et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst 1993;85:1121-1128
CrossRef | Web of Science | Medline31
Hayasaka S ,Mizuno K . Malignant melanoma of the choroid in a mother and retinoblastoma in her son. Br J Ophthalmol 1986;70:107-110
CrossRef | Web of Science | Medline32
Bataille V ,Hiles R ,Bishop JA . Retinoblastoma, melanoma and the atypical mole syndrome. Br J Dermatol 1995;132:134-138
CrossRef | Web of Science | Medline
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Smita Bhatia, Charles B. Pratt, Gerald B. Sharp, Leslie L. Robison. (1999) Family history of cancer in children and young adults with colorectal cancer. Medical and Pediatric Oncology 33:5, 470-475
CrossRef27
Jørgen H. Olsen, Lene Mellemkjaer, Gloria Gridley, Louise Brinton, Christoffer Johansen, Susanne Krüger Kjaer. (1999) Molar pregnancy and risk for cancer in women and their male partners. American Journal of Obstetrics and Gynecology 181:3, 630-634
CrossRef28
Kari Hemminki, Pauli Vaittinen. (1998) National database of familial cancer in Sweden. Genetic Epidemiology 15:3, 225-236
CrossRef29
Davide Brunetti, Paolo Tamaro, Furio Cavallieri, Giorgio Stanta. (1997) Cancer risk in first-degree relatives of children with malignant tumours (province of Trieste, Italy). International Journal of Cancer 73:6, 822-827
CrossRef30
A. Luz. (1997) Abschätzung des Krebsrisikos durch genetische Analyse?. Strahlentherapie und Onkologie 173:9, 444-456
CrossRef31
Steven A. Narod. (1996) Genetic epidemiology of childhood cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1288:3, F141-F150
CrossRef32
Tine Westergaard, Jørgen H. Olsen, Morten Frisch, Niels Kroman, Jan W. Nielsen, Mads Melbye. (1996) Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study. International Journal of Cancer 66:5, 627-631
CrossRef33
Hans H. Storm. (1996) Cancer registries in epidemiologic research. Cancer Causes and Control 7:3, 299-301
CrossRef34
M P Little, R Wakeford, M W Charles, M Andersson. (1996) A comparison of the risks of leukaemia and non-Hodgkin's lymphoma in the first generation offspring of the Danish Thorotrast patients with those observed in other studies of parental pre-conception irradiation. Journal of Radiological Protection 16:1, 25-36
CrossRef35
Sørensen, Thorkild I.A., . (1995) Is There an Inherited General Susceptibility to Cancer?. New England Journal of Medicine 333:24, 1633-1635
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