Testicular cancer, cryptorchidism, inguinal hernia, testicular atrophy, and genital malformations: case-control studies in Denmark.

To explore risk factors for testicular cancer and cryptorchidism, two parallel case-control studies were conducted in Denmark. The testicular cancer study was population-based and included 514 cases and 720 controls. The cryptorchidism study included 387 cases and 416 controls and was based on two hospital series of men treated for cryptorchidism and a control group sampled among residents in the Copenhagen area. The 2,037 men were interviewed by telephone. The relative risk (RR) of testicular cancer in men with treated or persisting cryptorchidism was 3.6 (95 percent confidence interval = 1.8-6.9), but no increase in risk was seen in the six to seven percent of the men who reported a history of undescended testes that descended spontaneously. The RR in men who were treated for cryptorchidism increased with age at treatment. This effect may be due wholly or in part to increased treatment of boys with testes that would have descended spontaneously if they had not been treated. Cryptorchidism and inguinal hernia may be confused and reported interchangeably. In the absence of cryptorchidism or testicular atrophy, clinical inguinal hernia was not associated with testicular cancer. Testicular atrophy was associated with both testicular cancer and cryptorchidism. Associations with other congenital malformations were few and based on small numbers.

Cancer of the male genital tract in Circumpolar Inuit.

In an international collaboration project we combined cancers of the male genital tract among Inuit identified from routine cancer registry systems in the Circumpolar region (Alaska, Canada and Greenland) and compared incidence rates with rates in Denmark, Connecticut (USA) and Canadian non-Inuit. We observed a low risk of prostate cancer (standardized incidence ratio (SIR) 0.2-0.3) and the incidence rate of 7.8 per 100 000 (world standard) is among the lowest in the world. Dietary and not diagnostic factors are likely explanations of this finding. Testicular cancer also occurred with low rates (SIR 0.3-0.7) although only significantly so when compared with Denmark and Connecticut (USA) which have some of the world's highest incidence rates of this cancer. Penile cancer occurred with relatively high risk (SIR 1.8-3.0) based on rates among non-Inuit. The incidence is, however, lower than anticipated considering the possibility for shared risk factors with cancer of the uterine cervix.

Genital anomalies and risk for testicular cancer in Danish men.

In a cohort of Danish boys characterized by (1) being born between 1941 and 1957, (2) having attended schools in a defined area of Denmark, and (3) having a school health record available, 183 were registered in the Danish Cancer Registry with testicular cancer diagnosed before January 1, 1985. We selected 366 age- and sex-matched controls from the same cohort. Using information recorded by school physicians, we performed logistic regression analyses to estimate the relative risks (RR) associated with various genital anomalies. We found the risk for testicular cancer to be raised for men with a history of cryptorchidism [RR = 5.2; 95% confidence interval (CI) = 2.1-13.0], inguinal hernia (RR = 1.8; 95% CI = 0.9-3.7), hypospadias (RR = 4.2; 95% CI = 0.4-42.7), and hydrocele (RR = 2.4; 95% CI = 0.6-9.0). We observed no decrease in the risk associated with cryptorchidism after correction of the maldescent in early childhood. The RR of testicular cancer in the contralateral, normally descended testis in unilateral cryptorchid men was increased to 3.6. The results add to the growing evidence for a common causal factor for both testicular cancer and cryptorchidism and support the findings from other studies of associations between other genital anomalies involving the closure of the processus vaginalis and the risk of testicular cancer.

Birth order and risk of testicular cancer.

To explore the etiology of testicular cancer, cases of testicular cancer were identified among members of a cohort of Danish boys born between 1941 and 1957 (inclusive), who had attended schools in Copenhagen and Gentofte and whose school health records were contained in an archive under the supervision of the Danish Cancer Registry. One hundred and eighty-three cases of testicular cancer diagnosed before 31 December 1984 were identified; 366 controls, matched to cases by sex and age, were selected from the same cohort. Information on potential risk factors and confounders was obtained from two sources: school health records and midwife protocols, both of which were recorded prior to the diagnosis of testicular cancer in cases. Relative risks (RR) approximated by the odds ratios were calculated and, in logistic regression analyses, adjustments were done for known or suspected confounders. A decreasing risk of testicular cancer with increasing birth order was observed (P = 0.020). Compared with being firstborn, being number four or more in birth order was associated with a significantly decreased RR for all testicular cancers (RR = 0.3, 95 percent confidence interval [CI] = 0.3-0.8) and testicular seminoma (RR = 0.1, CI = 0.02-0.9). No association was observed between high social class and the risk of testicular cancer (RR = 1.4, CI = 0.8-2.3); neither was age at which the study subjects had mumps or measles related to risk of testicular cancer. No cases of mumps orchitis were observed before or during school years. A slightly increased RR for testicular cancer among boys from small families could be explained by the association between family size and birth order.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in incidence of disease due to diagnostic drift: primary liver cancer in Denmark, 1943-85.

OBJECTIVE: To examine the extent to which changes in diagnostic methods and classification are responsible for the striking increase in incidence of primary liver cancer in Denmark since 1943. DESIGN: Analysis of the time trends in sex specific, age standardised incidence of primary liver cancer and unspecified liver cancer (either secondary without known primary cancer or not specified as primary cancer) in the entire population from 1943 to 1985. By review of the 727 notifications from three periods of 5 years (1948-52, 1963-7, and 1978-82) the changes in histological diagnosis and classification were assessed. SETTING: Denmark. SUBJECTS: Notifications of liver cancer to the Danish cancer registry. RESULTS: Concomitant with the increase in primary liver cancer, the incidence of the unspecified liver cancer declined. The proportion of histologically diagnosed primary liver cancer rose from 85% to 98%, whereas the proportion for unspecified liver cancer rose from 12% to 51%. When the proportion of primary versus unspecified liver cancer obtained by histological diagnosis was extrapolated to all cases, the annual incidence of primary liver cancer was 4.4 rather than 1.6 per 100,000 population in 1948-52 and 6.0 rather than 5.5 per 100,000 in 1978-82. CONCLUSION: The increase in the incidence of primary liver cancer may be much smaller than the numbers of registered cases indicate. This example emphasises the need to consider diagnostic drift in time trend studies of disease incidence.

Body size and cancer of the testis.

In the search for possible causes for the enormous increase in testicular cancer incidence in Denmark, we tested the hypothesis that a high fat or calorie intake in adolescence and consequently relative obesity is a promotional factor for testicular cancer. A total of 438 cases and three controls for each case were included in the study. Data originated from health examination of men liable for military service. Data were analysed by logistic regression analysis. No systematic statistically significant differences in body measurements [height, weight and body-mass index (weight/height2)] could be shown. Rather than being obese a slight trend was observed towards the future victims of testicular cancer being lighter, smaller and thinner than unaffected controls.

Month of birth and testicular cancer risk in Denmark.

On the basis of 40 years of national cancer registration, the authors analyzed the distribution of birth dates of patients with testicular cancer in the Danish male population, which has a particularly high incidence of this cancer. No significant peaks were identified, except for men with embryonal carcinomas born between 1950 and 1959, for whom a significant 12-month cycle was observed. This result differs from those of earlier studies. The number of cases of embryonal carcinomas in the 1950-1959 birth cohort is small, but it is possible that an etiologic factor that varies with season was present at the time. For all testicular cancers and for the three histologic subgroups analyzed, the authors found significant 2-month cycles. The biologic relevance of a 2-month cycle is not clear. It is concluded that there is little evidence to support the hypothesis of a systematic variation in month of birth among men with testicular cancer.

Primary squamous cell carcinoma of the rectum in Denmark.

Only a limited number of cases of primary squamous cell carcinoma (SCC) developed in the colon and rectum have been described in the world literature. This study represents the first population-based study of this rare cancer. Sixteen patients with primary SCC of the rectum diagnosed in the period 1978-1983 were identified from the Danish Cancer Registry. Eleven patients were excluded after revision of the histological specimens because the SCC in these cases were in connection with the squamous epithelium of the anal canal. SCC of the rectum in Denmark in the period 1978-1983 thus constituted 0.06% and 0.11% of the histologically verified rectal tumours in men and women, respectively. Case reports on these cases are given. One of the two males was homosexual and the other had never been married or lived with a woman. It is concluded that our findings support the hypothesis proposed by Austin that there may be an association between the frequency of anal intercourse and occurrence of squamous cell carcinoma of the rectum.

Cancer pattern among Greenlandic Inuit migrants in Denmark, 1968-1982.

For several cancer sites the incidence among Inuit (Eskimos) in Alaska, Canada and Greenland differs markedly from that in non-Inuit in adjacent areas. This is the first study of Inuit migrants. Among 11,571 Inuit Greenlandic people living in Denmark in the period 1968-1982 we found 69 cases of cancer. Significantly increased risks compared to the Danish population were found for cancer of the rectum (RR = 5.5) in males and for nasopharyngeal cancer (RR = 185.2) and cancer of the cervix uteri (RR = 1.9). The significance of these findings in relation to the role of environmental factors in the aetiology of cancer in Inuit is discussed.

Second cancer following cancer of the male genital system in Denmark, 1943-80.

The incidence of second primary cancers was investigated among 19,886 patients with prostate cancer. The analysis disclosed 594 new cancers, which was significantly less than the expected 1,176 cases (relative risk = 0.51). Deficits were observed for most sites but were only significant for cancers of the lip, lung, and gastrointestinal organs. The average age at diagnosis of prostate cancer was 72 years. It is likely that the apparent deficit in the incidence of second neoplasms resulted from less diagnostic aggressiveness in elderly patients with cancer compared with younger patients. The risk of developing a second primary cancer was also investigated in 4,290 men with testis cancer reported to the Danish Cancer Registry between 1943 and 1980. A significant 29% excess of second cancers was found (174 observed vs. 135 expected). A bimodal distribution of risk over time was found with a 67% excess seen among patients followed for 1-4 years that was mainly due to increased incidence of acute nonlymphocytic leukemia and malignant lymphomas. Among patients surviving 10 or more years, the overall excess of 32% observed was mainly due to cancers of the gastrointestinal tract and the urinary bladder. As part of the initial treatment for testis cancer, 82% of the patients received radiotherapy. Chemotherapy was rarely given before 1975 and then mostly to patients with a poor prognosis. Late effects of radiotherapy conceivably could account for some of the excess of second hematologic as well as solid neoplasms.

Second cancer following lymphatic and hematopoietic cancers in Denmark, 1943-80.

In Denmark, approximately 5% of all malignant neoplasms occur within the lymphatic and hematopoietic tissues. Between 1943 and 1980, 23,367 persons with these diseases fulfilled the criteria for entering the study. The risk of developing a second primary cancer was significantly increased only after Hodgkin's disease [relative risk (RR) = 1.6], whereas no increase was found after non-Hodgkin's lymphoma [(NHL); RR = 1.0] or leukemia (RR = 1.1), and a significant deficit occurred after multiple myeloma (RR = 0.8). All initial cancer sites showed a higher incidence of second primary cancers among males than females. Significant elevated risks for acute non-lymphocytic leukemia occurred after Hodgkin's disease (RR = 17), NHL (3.8), and multiple myeloma (9.1). Among persons initially diagnosed with leukemia, NHL was significantly elevated (RR = 2.6). However, these RR should be regarded as minimum figures due to the likelihood of serious underreporting of second primary hematologic cancers in Denmark. The secondary leukemias were likely induced by the treatment of the first primary cancer (chemotherapy, radiotherapy), but common etiologies, misclassification, or progression of the initial cancer cannot be ruled out entirely. Other second primary cancers found to be above expectation following Hodgkin's disease were cancers of the pancreas, lung, and urinary bladder. The risk for bladder cancer increased with time, which suggested a causal relation to radiation or chemotherapy, or both. Cancers of the colon and rectum following NHL and female breast cancer following leukemia occurred below expectation and remain unexplained.