Association of validated breast cancer susceptibility single nucleotide childhood traits

[Truncated abstract] Antenatal, early life, childhood and midlife factors have been consistently associated with the development of breast cancer suggesting that there are sensitive periods for the origins of breast carcinogenesis. Using extensive longitudinal data collected over a period of 20 years from the Western Australian Pregnancy Study (Raine) and the UK Avon Longitudinal Study of Parents and Child (ALSPAC), the thesis focuses on whether common genetic variants associated with breast cancer risk demonstrate pleiotropy, thereby affecting several distinct but unrelated phenotypes, over the life-course. The aims of the thesis were to evaluate the relationship of antenatal, early life and childhood growth phenotypes to genotypes associated with risk of breast cancer. Comprehensive epidemiological models of antenatal growth were developed that detected no associations with paternal size, thereby challenging the maternal conflict hypothesis. The results of the fetal growth analyses also threw new light on the determination of fetal body shape based on the sex of the fetus and exposure to an adverse intra-uterine environment. Female fetuses had a proportionally longer femur length, increasingly greater abdominal circumference over the gestation period and proportionally larger placental weight at birth compared to male fetuses who, conversely, invested in greater skeletal and leanbody mass at the expense of greater placental growth and fat reserves. Fetal adiposity increased with increasing placental weight and was greatest in the offspring of diabetic mothers. In addition, placental impairment (determined by Doppler flow rate) produced a similar pattern of disproportional fetal growth restriction as fetuses exposed to maternal hypoxia at altitude; linear growth was maintained at the expense of adiposity.