Abstract 1264: Dietary n-6 fatty acids and risk of hepatocellular carcinoma among Chinese in Singapore: The Singapore Chinese Health Study
Authors: Koh Woon-Puay , Dan Yock Young , Pan An , Yuan Jian-Min 
Published: May 2015

Abstract
Prospective epidemiologic data showed aspirin use was associated with a 49% reduction in the risk of hepatocellular carcinoma (HCC). Aspirin inhibits the COX-2 enzymatic pathway that converts arachidonic acid [an n-6 polyunsaturated fatty acid (FA) derived from other dietary n-6 FA including gamma-linolenic and linoleic acids] to prostaglandins, and the latter have in turn been implicated in chronic inflammation underlying carcinogenesis. Recent work on the lipidomic signature of lipid metabolism also suggests that long chain n-6 FA may play a role in HCC. However, little is known about the relation between dietary n-6 FA and risk of HCC. We examined this association using the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. Detailed information on current diet, assessed via a validated food frequency questionnaire, medical history and lifestyle factors were obtained through in-person interview at enrollment. As of 31 December 2010, after an average of 14 years of follow-up, we identified 486 subjects who had developed incident HCC via linkage with the Singapore Cancer Registry. We used the Cox regression methods to examine intake of energy-adjusted dietary FA in relation to HCC risk with adjustment for age at baseline, dialect, education, smoking status, intake of alcohol and coffee, daily energy intake and history of diabetes. Among all the dietary fat components examined, which included saturated, monounsaturated, total polyunsaturated, n-3 and n-6 FA, only n-6 fatty acid intake displayed a significant dose-dependent, positive association with HCC risk (p for trend=0.02). Compared to those in the lowest quartile, the hazard ratios [95% confidence interval (CI)] in quartiles 2, 3 and 4 were 1.23 (0.95-1.58), 1.32 (1.02-1.71), and 1.35 (1.04-1.76), respectively. Ration of n-6 to n-3 fatty acid intake was also positively associated with HCC risk although result was not statistically significant. When examined within a case-control set of 92 cases and 274 controls with serological biomarkers of hepatitis B and C infection nested within this cohort, the association between n-6 fatty acid and HCC risk was seen only in those negative for serology markers of hepatitis B or C infection (38 cases and 221 controls). Compared to less than median intake, those with higher intake had an odds ratio (95% CI) of 2.64 (1.19-5.88). Conversely, the association was null among subjects positive for serologic markers of hepatitis B or C infection [odds ratio of 0.94 (0.39-2.29)]. The result for the n-6 to n-3 fatty acid intake ratio was similar, compared to those with less than median value, those with higher ratios had an odds ratio (95% CI) of 2.79 (1.26-6.16) for HCC risk. Results from this study supports the hypothesis that n-6 fatty acid is implicated in the carcinogenesis of non-viral hepatitis related HCC.
Citation Format: Woon-Puay Koh, Yock Young Dan, An Pan, Jian-Min Yuan. Dietary n-6 fatty acids and risk of hepatocellular carcinoma among Chinese in Singapore: The Singapore Chinese Health Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1264. doi:10.1158/1538-7445.AM2014-1264