Chenjie Zeng

Disparities by race, age, and sex in the improvement of survival for major cancers: Results from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program in the United States, 1990 to 2010

IMPORTANCE Substantial progress has been made in cancer diagnosis and treatment, resulting in a steady improvement in cancer survival. The degree of improvement by age, race, and sex remains unclear. OBJECTIVE To quantify the degree of survival improvement over time by age, race, and sex in the United States. DESIGN, SETTING, AND PARTICIPANTS Longitudinal analyses of cancer follow-up data from 1990 to 2010, from 1.02 million patients who had been diagnosed as having cancer of the colon or rectum, breast, prostate, lung, liver, pancreas, or ovary from 1990 to 2009 and who were included in 1 of 9 population-based registries of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) and 95% CIs for cancer-specific death were estimated for patients diagnosed as having any of these cancers during 1995 to 1999, 2000 to 2004, and 2005 to 2009, compared with those diagnosed in 1990 to 1994. RESULTS Significant improvements in survival were found for cancers of the colon or rectum, breast, prostate, lung, and liver. Improvements were more pronounced for younger patients. For patients aged 50 to 64 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.57 (95% CI, 0.55-0.60), 0.48 (95% CI, 0.45-0.51), 0.61 (95% CI, 0.57-0.69), and 0.32 (95% CI, 0.30-0.36), for cancer of the colon or rectum, breast, liver, and prostate, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. However, the corresponding HRs (95% CIs) for elderly patients (those 75-85 years old) were only 0.88 (95% CI, 0.84-0.92), 0.88 (95% CI, 0.82-0.95), 0.76 (95% CI, 0.69-0.84), and 0.65 (95% CI, 0.61-0.70), for the same 4 cancer sites, respectively. A similar, although weaker, age-related period effect was observed for lung and pancreatic cancers. The adjusted HRs (95% CIs) for lung cancer were 0.75 (95% CI, 0.73-0.77) and 0.84 (95% CI, 0.81-0.86), respectively, for patients aged 50 to 64 years and 75 to 85 years diagnosed between 2005 and 2009, compared with the same age groups of patients diagnosed between 1990 and 1994 (0.73 [95% CI, 0.69-0.77] and 0.90 [95% CI, 0.85-0.95], respectively. Compared with whites or Asians, African Americans experienced greater improvement in prostate cancer survival. From 1990 to 2009, ovarian cancer survival declined among African Americans but improved among whites. No apparent sex difference in the degree of improvement for any non-sex-specific cancer was noted. CONCLUSIONS AND RELEVANCE Younger patients experienced greater benefit from recent oncology advances than elderly patients. African Americans experienced poorer survival than whites for all cancers, and the racial difference decreased for prostate cancer but increased for ovarian cancer. Identifying factors associated with varied improvement in cancer survival can inform future improvements in cancer care for all.

Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

Background:Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.Methods:We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.Results:No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ⩾62 years for LA (ORLA=1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (ORAA=1.05, 95%CI=1.02, 1.08; OREPA=1.04, 95%CI=1.01, 1.06; ORDPA=1.05, 95%CI=1.02, 1.08).Conclusion:Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.

Abstract 229: Genome-wide association study by colorectal carcinoma subtype

Over 50 genetic variants have been associated with colorectal cancer (CRC) risk through genome-wide association studies (GWAS), yet these variants represent only a fraction of the total estimated h ...

Abstract LB-370: Fine mapping of 32 breast cancer risk loci in women of East Asian ancestry

Background: Genome-wide association studies (GWAS) have identified multiple genetic susceptibility loci for breast cancer risk. The majority of these loci, however, were identified in studies conducted in European descendants. A comprehensive evaluation of these risk loci using densely genotyped data in East Asians may help to identify independent association signals and risk variants that are more closely related to breast cancer risk in East Asian women than those reported initially. Methods: We performed a fine-scale mapping of 32 breast cancer susceptibility loci identified in previous GWAS in 5,703 breast cancer cases and 5,766 controls in studies conducted in Shanghai, China, Nearly 4,100 variants in these 32 loci were genotyped. We imputed genotypes using the 1000 Genomes Project (Phase 3) as the reference. Included in this analysis were 4,086 genotyped and more than 17,000 well-imputed common variants. At each locus, analyses using logistic regression models were conducted to identify variants that better capture the association with breast cancer risk and new risk variants that are not correlated with the risk variants reported from the initial studies (index SNPs). To identify additional independent risk variants, logistic regression conditional on the most significantly associated variant was performed. Results: We identified risk variants that better captured the association than the index SNPs at 3 loci (2q35, rs1478596, OR = 1.14, P = 5.6×10-6; 6q25.1, rs9322344, OR = 0.89, P = 3.1×10-5;11q24.3, rs11221769, OR = 1.12, P = 6.1 ×10-5), new risk variants at 2 loci (1p13.2, rs3789614, OR = 1.31, P = 0.002; 2q31.1, rs117055746, OR = 0.87, P = 0.004), and independent risk variants at two loci (6q14.1, rs200626240, OR = 0.89, P = 0.001; 6q25.1 rs2982684, OR = 0.87, P = 2.7×10-5, Chr6:152107810, OR = 0.91, P = 1.4×10-4). Conclusion: This study identified multiple risk variants that were more relevant to East Asians than the index SNPs. These risk variants combined explained a further 2% of the familial relative risk in this population. This study highlighted the need of fine-mapping studies in non-European ancestral populations to search for additional risk variants. Citation Format: Chenjie Zeng, Qiuyin Cai, Jirong Long, Ying Zheng, Yong-Bing Xiang, Jiajun Shi, Xiao-Ou Shu, Wei Zheng. Fine mapping of 32 breast cancer risk loci in women of East Asian ancestry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-370.