Risk of sex-specific cancers in opposite-sex and same-sex twins in Denmark and Sweden

Background: Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone. Methods: This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. On the basis of the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins, whereas standardized incidence ratios (SIR) with95%confidence intervals (CI) were calculated for OS/SS twins compared with the general population. Results: A total of 18,001 cancers were identified during 1943- 2009.Nosignificant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All-cause cancer was slightly reduced for OS and SS twins compared with the general population, significant for OS males (SIR, 0.95; 95% CI, 0.92-0.98) and for SS males and females (SIR, 0.97; 95% CI, 0.94-0.99). Conclusions: Our data suggest that having a male co-twin-which may entail higher exposure to prenatal testosterone-does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. Impact: Findings are reassuring, as they fail to provide evidence for the hypothesis that endocrine or other difference in the in utero milieu affects the risk of sex-specific cancers.