Genetics, Caffeine Consumption, Height and Non-Melanoma Skin Cancer
Citation
Li, Xin. 2016. Genetics, Caffeine Consumption, Height and Non-Melanoma Skin Cancer. Doctoral dissertation, Harvard T.H. Chan School of Public Health.Abstract
Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma (BCC and SCC, respectively), is the most common malignancy among populations of European ancestry. It is estimated that over 2 million cases of NMSC occur each year in the United States, with the incidence continues to increase. This disease imposes a growing burden on healthcare system, making it an important public health issue. However, understanding of its etiology and biological mechanisms remains incomplete.In Chapter 1 of this dissertation, we applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis to identify potential novel biological pathways that are associated with BCC risk. We evaluated the associations of skin eSNPs with BCC among 2,323 cases and 7,275 controls of European ancestry, and assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, regulation of actin cytoskeleton, and basal cell carcinoma) and two GO pathways (cellular component disassembly involved in apoptosis, and nucleus organization) showed significant association with BCC risk. Our results indicate that genes that are undetectable by conventional genome-wide association studies (GWASs) are significantly associated with risk of BCC as groups.
In Chapter 2, we tested gene-caffeine consumption interaction on BCC risk in a genome-wide analysis. We determined that SNP rs142310826 shows a genome-wide significant interaction with caffeine consumption (p = 1.78x10-8 for interaction, p = 0.64 for heterogeneity between genders) on BCC risk. We also found several loci that modify the caffeine-BCC association differently in men and women. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in conventional GWASs.
In Chapter 3, we prospectively examined the risk of SCC and BCC in relation to adult height. After controlling for potential confounding factors, the hazard ratios were 1.09 (95% CI: 1.03, 1.16) and 1.10 (95% CI: 1.07, 1.12) for the associations between every 10cm increase in height and risk of SCC and BCC respectively. However, no significant association was observed between height-related SNPs and risk of these diseases.
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