British Journal of Cancer (2011) 104, 520 – 523 & 2011 Cancer Research UK All rights reserved 0007 – 0920/11 www.bjcancer.com Short Communication Does the association of education with breast cancer replicate within twin pairs? A register-based study on Danish female twins M Madsen*,1,6, PK Andersen2, M Gerster3, A-M Nybo Andersen4, K Christensen1,6, M Osler5,6 1Unit of Epidemiology, University of Southern Denmark, The Danish Twin Registry, DARC, University of Southern Denmark, J.B. Winsløwsvej 9B, DK-5000 Odense C, Denmark; 2Institute of Public Health, Division of Biostatistics, University of Copenhagen, Copenhagen, Denmark; 3Unit of Biostatistics, University of Southern Denmark, Odense, Denmark; 4Institute of Public Health, Division of Social Medicine, Copenhagen, Denmark; 5Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; 6Danish Aging Research Centre, Department of Epidemiology, University of Southern Denmark, J. B. Winslowsvej 9, DK-5000 Odense C, Denmark BACKGROUND: A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for. METHODS: We used data on education and other factors from the Danish Twin Registry, The Danish Cancer Registry, and official registers on a total of 16 310 twins. Unpaired and intrapair Cox regression analyses were compared. RESULTS: In the unpaired analysis, an educational gradient in breast cancer risk was found. Similar results were seen in the intrapair analyses of all twins, although no longer statistically significant. When intrapair analyses were stratified on zygosity, the effect of education was attenuated in the monozygotic twins. CONCLUSION: The main findings support an effect of education beyond shared familial factors. British Journal of Cancer (2011) 104, 520 – 523. doi:10.1038/sj.bjc.6606090 www.bjcancer.com & 2011 Cancer Research UK Keywords: twin study; education; social class; breast neoplasm E p i d e m i o l o g y In Denmark, breast cancer (BC) incidence has increased during recent decades, and it is now the most frequent cancer in women (Ferlay et al, 2007). In contrast to most health outcomes, a positive social gradient has been observed in BC, showing a higher risk in higher socio-economic position (SEP) groups (Kongevinas et al, 1997). Several BC risk factors are well established: high age at first birth (AFB), low parity (Ma et al, 2006), hormonal replacement therapy (Porch et al, 2002; Tjonneland et al, 2004), high body mass index (van den Brandt et al, 2000; Ahlgren et al, 2004), and high alcohol consumption (Boyle and Boffetta, 2009). In recent years, there has also been interest in in utero- and early-life factors, including high birth weight (Silva et al, 2008; Oberg et al, 2009). Moreover, evidence suggests that child growth and childhood diet may convey the risk (Frazier et al, 2003; Ahlgren et al 2004; De Stavola et al, 2004; Michels et al, 2006). The BC aetiology seems to be influenced by different exposures that exert their influence throughout the life course (Lynch and Smith, 2005). Although modest, a genetic component of BC has also been demonstrated. In a large Nordic twin study, non-shared environment was found to influence the risk of BC the most (explaining 67% of the variance), while shared environmental factors seemed to have a negligible role (Lichtenstein et al, 2000). This may suggest that adult factors have a much larger effect than early-life factors. However, the power to disentangle genetic and shared environmental effects in heritability studies is limited. *Correspondence: Dr M Madsen; E-mail: mimadsen@health.sdu.dk Revised 23 November 2010; accepted 14 December 2010 The observed social differentials in BC may be driven by socially patterned adult factors such as AFB and parity, as better-educated women are more likely to postpone their pregnancies and have fewer children. Alternatively, the differentials may be a result of selection processes in which underlying factors, such as genes or childhood environment, influence SEP and the risk of BC, thus creating a spurious association (Smith et al, 1994). Previous studies on SEP and cancer have mostly dealt with mortality as opposed to incidence, which may complicate the picture if the social patterning of incidence and survival from cancer differs. However, a recent study found no effect of SEP in childhood on BC incidence when adult SEP was adjusted for (de Kok et al, 2008). Twins provide a unique model to disentangle contributions from adult, childhood, and genetic factors as twins share their intrauterine- and early environment and are partly (dizygotic (DZ) twins) or fully (monozygotic (MZ) twins) matched on genetic setup. We aimed, by using education as an indicator of SEP, to separate the effect of SEP on BC from that of shared familial factors. MATERIALS AND METHODS In the Danish Twin Registry, all female twins born between 1921 and 1974 were considered for the study. After restrictions to sex- liked intact twin pairs of known zygosity, alive, and resident in Denmark at the beginning of follow-up (1 January 1980 or the date the participants turned 30 years if younger than 30 years in 1980) with no previous BC diagnosis and with full information on education, the final study population consisted of 16 310 twins, including 6268 MZ and 10 042 dizygotic same sex twins (DZSS).