522 Association of education with BC within twin pairs? M Madsen et al Table 2 Hazard ratios of breast cancer (1980 – 2006) according to educational status and length of education in a population of Danish female twins (N ¼ 16 310) showing results from Cox regression analyses stratified on zygosity Unpaired analysisa DZSS N ¼ 10 042 ALLc N ¼ 16 310 MZ N ¼ 6268 ALLc N ¼ 16 310 MZ N ¼ 6 268 HRd CI 95% Events HRd CI 95% Events HRd CI 95% Events HR CI 95% Events HR CI 95% Events HR CI 95% Events Educational statuse Primary 1 ref Secondary/tertiary 1.39 1.15 – 1.67 Length of educationf Number of yearsg 1.04 1.01 – 1.07 518 344 174 1 ref 1.37 1.09 – 1.71 1 ref 1.43 1.04 – 1.97 1 ref 1.38 0.95 – 2.01 1 ref 1.70 1.08 – 2.69 1 ref 0.82 0.41 – 1.67 1.03 1.00 – 1.07 1.07 1.02 – 1.12 1.04 0.97 – 1.11 1.06 0.98 – 1.14 0.99 0.88 – 1.11 36 80 Abbreviations: DZSS ¼ dizygotic same sex twins; MZ ¼ Monozygotic twins; CI ¼ confidence interval; HR ¼ hazard ratio. Bold numbers indicate statistical significance at 5% level. aUnpaired analysis treating twins as individuals taking interdependence of observations into account by including a cluster term. The interpretation of HR is the risk of breast cancer in an individual with a secondary or tertiary education compared to a random individual with a primary education. bIntrapair analysis of twins by inclusion of a strata statement. The interpretation of HR is the risk of breast cancer in a twin with a secondary or tertiary education compared to its co-twin with a primary education. cALL ¼ monozygotic+dizygotic twins. dAdjusted for calender time. eMeasured according to ISCED (International Standard Classification of Education). fMeasured as standard number years required to complete a given education. gQuantitive variable. Interpretation of HR is the increase in risk of breast cancer associated with one additional year of education 127 263 Intrapair analysisb DZSS N ¼ 10 042 91 183 E p i d e m i o l o g y effect of education is not due to confounding from familial factors. This accords with the Nordic twin study (Lichtenstein et al, 2000) that suggests that non-shared factors are most important risk factors for BC as in the study that showed no effect of childhood SEP on incidence, when adult factors were adjusted for (de Kok et al, 2008). When MZ twins were analysed separately, the association was completely attenuated. However, as only few MZ twin pairs were available for the intrapair analysis, this is likely a chance finding. If not, the results are suggestive of underlying genetic factors associated with both a high education and a high risk of BC. The fact that no partial attenuation was observed in DZSS twins, contrary to expectation, might be explained by the presence of complex gene – gene interactions where several genes need to be present simultaneously in order for a phenotype to occur. Alternatively, if MZ twins also share their environment more closely than DZSS twins (Horwitz et al, 2003), for example fertility patterns, this could account for the observed differences in attenuation of effect between MZ and DZSS twins. However, this was not supported in our data set where parity and AFB did not have a statistically significant impact on the risk of BC. This study is the first to use the discordant twin-pair design to examine social inequality in BC. Several previous studies have used this approach to address causality in the social patterning of health and disease, but the population size available for this study allowed us to investigate a hard end point such as BC, which presents an interesting hypothesis because of its curious positive association with SEP. The prospective design and almost complete information in the registers ensure valid information REFERENCES Ahlgren M, Melbye M, Wohlfahrt J, Sørensen TI (2004) Growth patterns and the risk of breast cancer in women. N Engl J Med 351: 1619 – 1626 Boyle P, Boffetta P (2009) Alcohol consumption and breast cancer risk. Breast Cancer Res 11(Suppl 3): S3 Carlsen K, Høybye MT, Dalton SO, Tjønneland A (2008) Social inequality and incidence of and survival from breast cancer in a population-based study in Denmark, 1994 – 2003. Eur J Cancer 44: 1996 – 2002 de Kok IM, van Lenthe FJ, Avendano M, Louwman M, Coebergh JW, Mackenbach JP (2008) Childhood social class and cancer incidence: results of the globe study. Soc Sci Med 66: 1131 – 1139 British Journal of Cancer (2011) 104(3), 520 – 523 about educational status and BC in this largely unselected twin population. A key assumption in the discordant twin-pair logic is that twins who have grown up together are matched on early environment. Survey data indicate that this was the case for about 98% of the population (Madsen et al, 2010), so we do not expect this to be an important source of bias. Selection is another relevant issue. Twins who are discordant on education may comprise a selected group as they have obtained different educational statuses in spite of their common background and may not be representative of the twin population at large. Nevertheless, the discordant twin-pair method offers an exceptional opportunity to enhance validity in non-experimental designs. In conclusion, the finding of an effect of education in the combined intrapair analysis suggests that education has an effect on BC risk beyond shared familial factors; parity and AFB did not seem to be driving this association. The finding of an attenuation of effect in MZ twins, suggesting genetic confounding, may serve as a hypothesis for testing in larger data sets. ACKNOWLEDGEMENTS The Danish Aging Research Center is supported by a grant from the VELUX Foundation (95-103-11419) and from the Danish Cancer Society (SU08001). We thank Dorthe Almind Pedersen, MSc for her valuable help with the management of the data. Conflict of interest The authors declare no conflict of interest. De Stavola BL, dos Santos Silva I, McCormack V, Hardy RJ, Kuh DJ, Wadsworth ME (2004) Childhood growth and breast cancer. 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