Hadjisavvas et al. BMC Cancer 2010, 10:447 http://www.biomedcentral.com/1471-2407/10/447 Page 6 of 10 Table 3 Odds ratios (95% CI) of breast cancer by participants characteristics before and after adjusting for the effect of all other in a multivariable model Multivariable (N = 2020)2, 6 p-value3 p-value3 Risk factor Education Marital status BMI Family history of breast cancer Age at menarche (years) Age at 1st pregnancy (years) Breastfeeding5 Oral contraceptive use HRT use (months) Exercise Smoking Primary Secondary Tertiary University Married Widowed/Divorced Single <25 25-30 ≥30 No Yes ≤11 12-14 ≥15 <30 ≥30 Never4 No Yes No Yes Never <6 6-60 ≥60 No Yes Never Past/Current Univariable1 OR (95%CI) 1.00 1.17 (0.96,1.45) 1.09 (0.81,1.45) 1.35 (1.00,1.82) 1.00 1.08 (0.82,1.42) 1.55 (1.02,2.34) 1.00 0.80 (0.64,0.98) 1.21 (0.96,1.53) 1.00 1.68 (1.29,2.19) 1.00 0.80 (0.62,1.03) 0.61 (0.44,0.84) 1.00 1.36 (1.04,1.77) 1.51 (1.08,2.12) 1.00 0.63 (0.45,0.89) 1.00 1.03 (0.86,1.26) 1.00 0.63 (0.42,0.95) 0.49 (0.37,0.65) 0.50 (0.34,0.72) 1.00 0.86 (0.72,1.01) 1.00 1.24 (1.01,1.53) 0.07 0.57 0.04 0.11* <0.001 <0.01 <0.01 <0.01 0.70 <0.001 0.07 0.05 OR (95% CI) 1.18 (0.94,1.48) 1.12 (0.81,1.53) 1.40 (1.00,1,95) 1.06 (0.78,1.44) 1.28 (0.69,2.35) 0.86 (0.69,1.07) 1.22 (0.95,1.56) 1.64 (1.23,2.19) 0.82 (0.62,1.10) 0.64 (0.45,0.92) 1.25 (0.93,1.68) 0.93 (0.57,1.54) 0.74 (0.59,0.92) 1.02 (0.83,1.27) 0.67 (0.42,1.05) 0.47 (0.35,0.64) 0.53 (0.35,0.79) 0.94 (0.78, 1.13) 1.16 (0.91,1.47) 0.08 0.84 0.43 0.14* 0.001 0.01 0.14 0.76 0.01 0.84 <0.001 0.48 0.23 Notes: 1In all cases, models were adjusted for age. Both univariable and multivariable inferences remain largely unaffected when restricting the analyses to ages 45-64. 2Further adjusting for the effect of all other risk factors considered here. 3P-value for difference between levels of binary/nominal variables (e.g. family history) or p-value for linear trend across ordinal categorical variables (e.g. age at menarche or age at 1st pregnancy). 4The variable ‘pregnancy’ was not included in the multivariable model as its effect is captured accordingly by category ‘never’ of the variable “age at 1st pregnancy”. 5Odds ratio of the combined effect of breastfeeding after adjusting for pregnancy in a logistic model with an interaction term between the two variables but no main effect for breastfeeding. 6The p-value of the Pearson c2 goodness-of-fit test was 0.18 in the case of the full model and 0.55 for the model where only statistically significant variables were included (i.e. family history, breastfeeding, age at menarche and HRT use), in both cases suggesting a reasonable fit of the model *Evidence of non-linearity based on Likelihood Ratio Test comparing the goodness of fit of model with ordered categories Vs linear term across categories. and breastfeeding. In fact, these associations persisted after adjusting for the effect of all other factors. For instance, the adjusted odds ratio for family history was 1.64 (95% CI 1.23-2.19) while for breastfeeding this fig- ure was 0.74 (95% CI 0.59-0.92). Finally, a statistically significant trend with age at menarche and breast cancer risk was also observed. Women who started menstruat- ing earlier than the age of 11 had an increased risk for breast cancer compared to women who started menstru- ating later, even after adjusting for the effect of all other risk factors. Adjusted odds ratio in women who started menstruating between the ages 12-14 was 0.82 (95%CI 0.62-1.10) and 0.64 (95%CI 0.45-0.82) in those who started after the age of 15 years; p-value for linear trend < 0.01. None or only weak associations were observed between breast cancer risk and other risk factors investi- gated, for instance BMI, age at first pregnancy, smoking, exercise or use of oral contraceptives. Surprisingly, more controls (28.8%) than cases (15.5%) reported taking hor- mone replacement therapy (HRT). The inverse associa- tion persisted in the fully adjusted model, and in fact