La representación del indígena y el desnudo en las obras de Luis Mideros

There are several limitations to this study. The LIBCSP study population includes primarily Caucasian and postmenopausal women; therefore examination of potential racial differences was not possible. However, the results are generalizable to the subgroup of women who are at high risk for developing breast cancer in the U.S. [1].

For the case-control approach utilized in Aim 1, it is not possible to rule out recall bias, where it is possible that cases and controls may differentially recall foods high PUFA content. Also, a single dietary assessment via FFQ may not necessarily reflect diet during the etiologically relevant time period for breast cancer development. Similarly with regard to possible measurement error for Aim 2 follow-up approach, a one-time dietary assessment via FFQ is unable to assess changes in diet that may have occurred following breast cancer diagnosis. Although, a recent study has reported that intake of oily fish and fish oil increases post breast cancer diagnosis [420], thus suggesting that the estimate reported in this

dissertation for PUFA intake near time of diagnosis may be conservative.

Another limitation, relevant for both Aims 1 and 2, is the potential errors associated with dietary PUFA assessment via linkage with the USDA database. It is possible that the PUFA content in foods available in the USDA database differs from those actually consumed by LIBCSP participants. This could be due to a variety of reasons, including geographic differences in harvesting, storage, processing, and cooking methods [147, 417, 418]. For example, the nutrient composition of wild versus farmed fish of the same species differs substantially, where the farmed fish tend to contain lower amounts of LC ω-3 PUFAs [421]. Furthermore, the food sources for various ω-3 PUFA subtypes differ, and thus ω-3 content

obtained from these different sources could vary due to differences in food storage. For example, ALA is primarily obtained via vegetable and plant-derived oils, which are prone to oxidation due to prolonged storage [417]. Any observed benefit of ALA may be masked due to oxidation-induced ALA loss, thus further lowering formation of downstream LC ω-3 PUFAs resulting from ALA metabolism. However, absolute PUFA measurement error may be less of a concern since this dissertation considered PUFA via relative ranking of

individuals, using quartiles.

Another concern regarding PUFA measurement for Aims 1 and 2 is that the parent LIBCSP did not include assessment of consumption of different fish species, other than tuna. Levels of LC ω-3 PUFA differ by fish species [419]. Tuna, however, is the most common fish consumed in the U.S. and is a major food source of LC ω-3 PUFA [391]. Nonetheless, exposure assessment would have been improved if the LIBCSP participants had been also asked about their consumption of other specific fish species that are also high in LC ω-3 and may be commonly consumed in the U.S., such as salmon (rather than grouping all other fish species together). Additionally, although LIBCSP participants were queried about their cooking practices, the prevalence of fish intake was relatively low, which limits inferences regarding the impact of cooking methods due to small sample sizes. However, even with a larger sample, more detailed information would be required on factors affecting PUFA content (e.g., cooking time, type of oil used if fried, type of fish consumed) in order to more accurately assess the impact of different cooking methods on PUFA content, and its

subsequent relation with breast cancer risk and mortality.

Another limitation of this dissertation is the potential for inadequate coverage of genes involved in related biologic pathways. Although key putatively functional SNPs

involved in relevant pathways were considered (i.e., inflammation, oxidative stress, estrogen metabolism), it remains possible that some PUFA-gene interactions may have been missed due to failure to consider other relevant SNPs. For example, genes involved in the in vivo

metabolism of PUFA, namely LA and ALA (Figure 1.2) may interact with PUFAs to influence breast carcinogenesis, given their role in PUFA bioavailability. The efficiency of enzymes involved in this metabolism, in combination with dietary intake of PUFAs could influence consequent eicosanoid production. For example, it has been reported that the conversion of ALA into LC ω-3 is highly inefficient in populations consuming high ω-6 [150], thus further hindering the potential benefit derived from ALA consumption. However, a recent dietary intervention conducted among subjects with high ω-6 intake at baseline, observed increases in LC ω-3 PUFA plasma concentrations among subjects who lowered their ω-6 intake, thus suggesting improved enzyme efficiency in ALA to LC ω-3 PUFA metabolism in populations consuming high ω-6 [416]. Thus, consideration of these

additional genes, in concert with dietary intake of PUFAs, may further elucidate the relation between PUFAs and breast cancer.

Finally, this dissertation had limited study power to make inferences regarding breast- cancer specific mortality, because of the low number of deaths due to breast cancer in the LIBCSP study population even after 15 years of follow-up. However, the magnitude of the effect estimates for breast cancer-specific mortality was similar to those for all-cause mortality, for both 5-year survival as well as the entire 15-year follow-up. Thus, these findings are consistent with the proposed biology of PUFAs when considering the relation with breast-cancer specific mortality, though estimates were imprecise.