Testicular cancer : new etiological understanding of the epidemic

The incidence of testicular cancer has increased dramatically for decades, but what causes this increase is not known. The aim of this thesis was to find some explanation for the increasing rates, and to understand more about the mechanisms that can cause testicular cancer. We have conducted a series of epidemiological studies to try to reach this goal.

First, we investigated the relevance of Clemmesen s hypothesis that smoking during pregnancy can cause testicular cancer in the offspring. Using data from the Nordic Cancer Registries and from previous smoking surveys, we could investigate if there is a correlation between smoking habits among women at fertile ages and testicular cancer incidence among their presumed offspring. In support of the Clemmesen hypothesis, we found, with the exception of Finland, a strong both geographical and temporal correlation between female smoking prevalence and testicular cancer incidence in the Nordic countries.

Second, we tested the same hypothesis on the individual level. Using data from the Swedish Cancer Registry and from the Swedish Medical Birth Register, we conducted a population-based case-control study on 192 cases of testicular cancer, and 494 matched controls, born in Sweden in 1973 onwards. Data on smoking during pregnancy, recorded already when the mothers were pregnant, was manually retrieved from the delivery archives throughout Sweden. We found no association between pregnancy smoking and risk of testicular cancer, and concluded that the epidemic rise in testicular cancer is not due to the surge in smoking among women.

Third, using data from different Swedish registries, we could construct a cohort of almost 17,000 men surgically treated for undescended testis between 1964 and 1999. The men in the cohort were followed up for the occurrence and of testicular cancer, and we investigated if age at surgical correction of undescended testis affect the risk of developing testicular cancer in adulthood. We found that the risk among men who were treated after 13 years of age was twice that among men treated before 13 years of age. These results indicate that treatment before puberty decreases the risk of developing cancer, and that the misplacement of the testis is a factor in the development of testicular cancer.

Fourth, we used the same design and study subjects as in the second study, but with an additional 101 cases and 367 controls. We aimed at investigating if signs of placental malfunction, such as pregnancy induced hypertension and preeclampsia, are related to the risk of testicular cancer. We found a more than threefold decrease in risk among sons exposed to severe gestational hypertension, but a 60 percent increased risk among the sons of women with mild gestational hypertension. And the results for preeclampsia were similar. We speculate that the hormonal changes that seem to occur in severe hypertensive conditions during pregnancy are associated with a decreased risk of testicular cancer.

List of scientific papers

I. Pettersson A, Kaijser M, Richiardi L, Askling J, Ekbom A, Akre O (2004). "Women smoking and testicular cancer: one epidemic causing another?" Int J Cancer 109(6): 941-4
https://pubmed.ncbi.nlm.nih.gov/15027129

II. Pettersson A, Akre O, Richiardi L, Ekbom A, Kaijser M (2007). "Maternal smoking and the epidemic of testicular cancer--a nested case-control study." Int J Cancer 120(9): 2044-6
https://pubmed.ncbi.nlm.nih.gov/17278105

III. Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O (2007). "Age at surgery for undescended testis and risk of testicular cancer." N Engl J Med 356(18): 1835-41
https://pubmed.ncbi.nlm.nih.gov/17476009

IV. Pettersson A, Richiardi L, Cnattingius S, Kaijser M, Akre O (2008). "Gestational hypertension, preeclampsia, and risk of testicular cancer." Cancer Res 68(21): 8832-6
https://pubmed.ncbi.nlm.nih.gov/18974126