Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer

We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case–control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model.One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p？=？0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction？=？0.03). There were no significant interactions after correction for multiple testing.We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.Genome wide association studies (GWAS), have discovered several new genetic polymorphisms affecting breast cancer risk [1-3]. Even though these individual risk-factors each confer quite small increases in risk, a positive association is seen between the number of risk alleles carried and risk for breast cancer [4,5].The phenotypic variables height, body mass index (BMI) and use of hormone replacement therapy (HRT) reflect to varying degrees genetic background and environmental exposure. Both height and BMI have previously been shown to associate with breast cancer [6,7]. Increase in height has been shown to yield a proportional increase in breast cancer risk and obese women have a greater risk to contract postmenopausal breast cancer. Increased risk