ABSTRACT
BACKGROUND: Five single nucleotide polymorphisms (SNPs) were previously reported to be associated with thyroid cancer in European populations in two genome-wide association studies (GWAS): rs965513 (9q22.33), rs944289 (14q13.3), rs116909374 (14q13.3), rs966423 (2q35) and rs2439302 (8p12). Only the first two SNPs have been validated in independent populations and none were replicated in Chinese populations. METHODS: The above five SNPs were genotyped in 845 papillary thyroid cancer (PTC) and 503 benign thyroid tumour (BN) patients and 1005 controls in a Chinese population using the SNaPshot multiplex single nucleotide extension system. RESULTS: Significant associations were detected among PTC and rs944289 (p=8.007e-11), rs965513 (p=1.013e-4), rs966423 (p=1.688e-3) and rs2439302 (p=1.096e-4) in a dominant model, while the rs116909374 SNP was not detected in the Chinese population. The PTC risk increased with rise in accumulative numbers of risk alleles carried by individuals (p=5.929e-13). The PTC OR of carriers of six risk alleles (1.4% of the control population) was 23.587 compared with non-risk homozygotes (1.0% of the control population, with zero risk alleles). No individuals were homozygous for all the four SNPs (carriers of eight risk alleles) and only three PTC cases were carriers of seven risk alleles. A significant association between 14q13.3 SNP rs944289T and BN was also found (p=0.0014). CONCLUSIONS: Four candidate loci, rs965513 (9q22.33), rs944289 (14q13.3), rs966423 (2q35) and rs2439302 (8p12), identified by GWAS for PTC risk were confirmed in a Chinese population. The PTC risk of accumulative risk allele carriers increased with the number of risk alleles.
Subject(s)
Asian People/genetics , Carcinoma/genetics , Genetic Loci , Genetic Predisposition to Disease , Genome-Wide Association Study , Thyroid Neoplasms/genetics , Adult , Aged , Alleles , Carcinoma, Papillary , Case-Control Studies , China , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 8 , Chromosomes, Human, Pair 9 , Computational Biology/methods , Female , Genotype , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Thyroid Cancer, PapillaryABSTRACT
OBJECTIVE: To analyze the impact of the lymph node ratio (LNR, ratio of metastatic to examined nodes) on the prognosis of hypopharyngeal cancer patients. METHODS: SEER (Surveillance, Epidemiology and End Results)-registered hypopharyngeal cancer patients with lymph node metastasis were evaluated using multivariate Cox regression analysis to identify the prognostic role of the LNR. The categorical LNR was compared with the continuous LNR and pN classifications to predict cause-specific survival (CSS) and overall survival (OS) rates of hypopharyngeal cancer patients. RESULTS: Multivariate analysis of 916 pN+ hypopharyngeal cancer cases identified race, primary site, radiation sequence, T classification, N classification, M classification, the number of regional lymph nodes examined, the continuous LNR (Hazard ratio 2.415, 95% CI 1.707-3.416, P<0.001) and age as prognostic variables that were associated with CSS in hypopharyngeal cancer. The categorical LNR showed a higher C-index and lower Akaike information criterion (AIC) value than the continuous LNR. When patients (n = 1152) were classified into four risk groups according to LNR, R0 (LNR = 0), R1 (LNR ≤ 0.05), R2 (LNR 0.05-0.30) and R3 (LNR >0.30), the Cox regression model for CSS and OS using the R classification had a higher C-index value and lower AIC value than the model using the pN classification. Significant improvements in both CSS and OS were found for R2 and R3 patients with postoperative radiotherapy. CONCLUSIONS: LNR is a significant prognostic factor for the survival of hypopharyngeal cancer patients. Using the cutoff points 0.05/0.30, the R classification was more accurate than the pN classification in predicting survival and can be used to select high risk patients for postoperative treatment.
