Introduction 1 2 3 4 5 6 7 PvuII XbaI 8 9 10 XbaI PvuII 4 9 10 XbaI 11 12 4 13 14 15 14 The aim of our study was to evaluate the effect of these polymorphisms on breast cancer risk by performing an association analysis in a population based study of Caucasian postmenopausal women. Further, we performed meta-analyses of all available published data on these polymorphisms and the risk of breast cancer. Materials and methods Study population and measurements 16 17 Case identification and validation Three different databases were used for patient identification. First, cases diagnosed by general practitioners in the research area (Ommoord) were collected (International Classification of Primary Care (code X76)). Second, the Dutch National Registry of all hospital admissions (LMR) was consulted to detect all malignancy related hospital admissions for study participants. Finally, regional pathology databases were linked to the Rotterdam Study to identify patients. Subsequently, breast cancer cases were validated by a physician on the basis of medical records of the general practitioner, discharge letters and pathology reports. Only pathologically confirmed cases were considered in the analysis. The index date was defined as the earliest date found in the pathology report. Genotyping & data analysis PvuII XbaI 14 PvuII XbaI 14 18 Meta-analysis PvuII XbaI . 19 I 2 20 Results P X 2 P PvuII X 2 P XbaI 1 P P P P P Table 1 General characteristics of the study population Cases Controls Total Total studied (%) 190 (4.7%) 3513 (95.3) 3703 Mean age of entry (SD)* 67.80 (7.7) 70.36 (9.6) 70.24 (9.6) Mean age at death (SD)* 77.30 (8.6) 84.46 (8.7) 84.12 (8.8) Mean age at menarche (SD) 13.57 (1.7) 13.68 (1.8) 13.67 (1.8) Mean age at menopause (SD)* 49.51 (4.8) 52.19 (13.6) 52.07 (13.3) Mean number of children (SD)* 1.77 (1.6) 2.12 (1.7) 2.10 (1.7) Parity (SD) (≥1 child)* 121 (71.6) 2640 (79.4) 2761 (79) Hormone replacement therapy(%) 27 (21.1) 504 (19.5) 531 (19.6) Mean BMI (SD) 27.10 (3.9) 26.67 (4.1) 26.69 (4.1) Mean WHR (SD) 0.87 (.09) 0.87 (.09) 0.87 (.09) P PvuII P XbaI P 2 PvuII XbaI PvuII P XbaI P Table 2 PvuII XbaI Overall Incident Prevalent PvuII TT Ref Ref Ref TC 0.9 (0.6–1.4) 1.0 (0.6–1.6) 0.8 (0.3–2.1) CC 1.4 (0.8–2.2) 1.4 (0.8–2.5) 1.2 (0.4–3.3) XbaI AA Ref Ref Ref GA 1.2 (0.8–1.7) 1.3 (0.8–2.0) 0.8 (0.4–1.9) GG 1.3 (0.7–2.2) 1.5 (0.8–2.8) 0.5 (0.2–2.4) XbaI PvuII 4 9 12 21 24 11 4 9 10 XbaI PvuII 1 2 Fig. 1 XbaI Fig. 2 PvuII Discussion XbaI PvuII XbaI PvuII 13 One of the limitations of our study is the limited number of breast cancer cases present in our population. Nevertheless, we have sufficient power (β = 0.8) to detect effects of 1.6 or higher. We further conducted meta-analyses off all studies conducted to date. Our data suggests that these two polymorphisms do not play a role in the susceptibility of breast cancer in elderly Caucasian women.