Associations between serum vitamin D, genetic polymorphisms in the vitamin D pathway, and sarcopenia with overall and breast cancer-specific mortality in a cohort of breast cancer survivors.

摘要

Of the estimated 11.9 million cancer survivors in the United States, breast cancer survivors make up the largest group, approximately 22%. In response to the growing number of cancer survivors, public health programs are expanding their focus to include cancer survivorship. The objective of this dissertation was to investigate the degree to which vitamin D, genetic polymorphisms of vitamin D-related genes and body composition can impact survival in women diagnosed with breast cancer. This dissertation examined how vitamin D status, genetic variation in five candidate genes related to vitamin D metabolism and depleted muscle mass, or sarcopenia, are associated with mortality in the Healthy, Eating, Activity and Lifestyle (HEAL) Study, a multi-ethnic cohort of breast cancer survivors.;The first study (Chapter 1) tested associations between vitamin D status and mortality risk and found that women with serum 25(OH)D >30ng/mL had a decreased risk of overall mortality vs. women with serum 25(OH)D 20ng/mL. Adjustment for traditional prognostic factors attenuated the association. We found a similar non-statistically significant association with breast cancer-specific mortality. The second study (Chapter 2) tested associations between single nucleotide polymorphisms (SNPs) in five candidate vitamin D-related genes (i.e, CYP24A1, CYP27A1, CYP27B1 , GC and VDR) and serum 25(OH)D concentrations, and mortality risk. Two SNPs in GC, rs7041 and rs12512631, were associated with a modest increase in serum 25(OH)D. Further, women with rs7041 SNP C allele (TC or CC) had a decreased risk of overall and breast cancer-specific mortality vs. homozygous SNP T allele. We found no association between rs12512631 genotype and overall mortality and an increased risk of breast cancer-specific mortality in women with SNP G allele vs. homozygous SNP T allele. The third study (Chapter 3) determined the prevalence of sarcopenia in this study sample and examined the association between sarcopenic status and mortality. Sarcopenia, regardless of adiposity, was associated with an increased risk of overall mortality and may be associated with breast cancer-specific mortality. These studies contribute to the collective understanding of how certain nutritional, genetic and anthropometric factors may explain variation in mortality among women diagnosed with breast cancer.