Abstract 4630: Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese

Abstract

Abstract Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in Southern China with varying incidence rates among Han Chinese in different geographic regions. Recently, three independent genome-wide association studies (GWAS) confirmed that the HLA-A was the main risk gene of NPC. However, studies from regions with different incidence rates led to contradictory claims regarding whether HLA-A was the sole risk gene and the association of rs29232 was independent from the HLA-A effect in chromosome 6p21.3 region. To explore whether the differences were caused by genetic factors underlying the varying incidence rates by region in NPC incidence, we performed a meta-analysis by selecting 5 single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 from 3 published GWAS studies and 3 published case-control studies from Southern China (Taiwan, Guangdong and Guangxi) involving 7 828 NPC patients and 8 813 healthy controls from Han Chinese. The rs29232 SNP exhibited a moderate level of heterogeneity (I2 = 43%) that disappeared (I2 = 0% and 4%) after stratifying the studies according to moderate- and high-incidence NPC regions. The estimated odds ratio (OR) of rs29232 (OR: 1.70, 95% confidence interval [CI]: 1.47-1.95) was higher in the moderate-incidence region than in the high-incidence region (OR: 1.42, 95% CI: 1.30-1.56). The heterogeneity revealed by meta-analysis of rs29232 might be associated with differences in NPC incidence in Han Chinese between geographic regions. Therefore, we postulate that moderate heterogeneity in rs29232 might contribute to the varying incidence rates between regions due to a genetic cause in NPC incidence. The higher OR of rs29232 and the fact that it was independent of the HLA-A effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC in a moderate-incidence population than to a high-incidence population. To our knowledge, this is the first study to demonstrate that genetic factors might involve in the varying disease incidence rates by region. This further suggests that the disease incidence rate should be considered as a potential confounding factor when conducting large, cross-region meta-analysis in NPC. Citation Format: Wen-Hui Su, Chi-Cking Chiu, Yin Yao Shugart. Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4630. doi:10.1158/1538-7445.AM2015-4630