6. FUTURE DIRECTIONS While molecular epidemiology studies hold the promise of elucidating mechanisms behind breast cancer risk factors, it is still subject to limitations of traditional epidemiological studies. Much of the molecular epidemiology literature is rife with inconsistencies, as described in this chapter. This is likely due to the small sample sizes of the studies, which result in low power to detect associations. A recent article described the sobering numbers of participants required to detect stable estimates from epidemiological studies of gene-environment interactions (219).

Additionally, examining one gene at a time in relation to breast cancer risk is likely too simplistic. Future studies should consider the roles of other genes involved in metabolic pathways and examine several genes at a time in relation to cancer risk (220). Multigenic studies have been conducted recently with suggestive findings. Feigelson et al. examined CYP17 and 17p-HSD in combination, in relation to breast cancer risk in a large, multiethnic population. They demonstrated an increased risk from high-risk alleles limited to advanced stage breast cancer and postulated that these tumors may be more aggressive as a result of increased estrogenic exposure (221). Huang et al. also considered the effect of several estrogen-metabolizing genes involved at different points within the pathway, including CYP17, CYP1A1, and COMT (222). A trend in increasing risk was observed with increasing number of at risk genotypes. This effect was especially pronounced in women with prolonged estrogen exposure, providing further support of the possibility that breast cancer can be initiated by estrogen exposure and is influenced by genotypes. Eventually, techniques that provide simultaneous assessment of tens-to-hundreds-to-thousands of genes at a time will be useful in studies of cancer. However, it is unrealistic to anticipate the incorporation of a large number of genes into current molecular epidemiological practice, since proper statistical methods are not in place.