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Residents of Qidong, China, located at the mouth of the Yangtze River, are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic and environmental factors. As tracked by their cancer registry, there are extraordinary changes in the China age-standardized incidence rates for the two leading cancer killers in the Qidong region: one going down and the other one up, liver and lung cancer respectively. In endemic areas such as Qidong, liver cancer arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Agricultural and economic reforms in the 1980s promoted a switch from maize to rice as the dietary staple, with concomitant >40-fold decreases in aflatoxin exposure over this period as measured by aflatoxin-albumin adducts in archived serum samples. Universal, subsidized vaccination against HBV was initiated in the early 2000s and likely does not account for the 45% drop in liver cancer incidence over the past quarter century, but augurs well for the future. Age standardized incidence rates for lung cancer, by contrast, have tripled in men over this period, reflecting the high prevalence of smoking (~60%) in adult males and increasing numbers of cigarettes smoked. Women in Qidong, on the other hand rarely smoke. Nonetheless, their rates of lung cancer incidence have doubled over the past decade only, perhaps related to changing patterns of exposures to indoor and outdoor air pollution. Approaches to modulate the impact of these exposures through chemopreventive interventions will be presented. Both primary and secondary prevention strategies appear to offer opportunities for risk reduction in this shifting landscape of exposures to environmental carcinogens. Citation Format: Thomas W. Kensler, Jian-Guo Chen, Tao-Yang Chen, Patricia Egner, Derek Ng, Alvaro Munoz, John Groopman. Changing landscape of environmental carcinogenesis in Qidong, China: Lessons for prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL02-03.

To examine the associations between abnormal birth history (birth weight2500 g, gestational age36 weeks, or small for gestational age), blood pressure (BP), and renal function among 332 participants (97 with abnormal and 235 with normal birth history) in the Chronic Kidney Disease in Children Study, a cohort of children with chronic kidney disease (CKD).Casual and 24-hour ambulatory BP were obtained. Glomerular filtration rate (GFR) was determined by iohexol disappearance. Confounders (birth and maternal characteristics, socioeconomic status) were used to generate predicted probabilities of abnormal birth history for propensity score matching. Weighted linear and logistic regression models with adjustment for quintiles of propensity scores and CKD diagnosis were used to assess the impact of birth history on BP and GFR.Age at enrollment, percent with glomerular disease, and baseline GFR were similar between the groups. Those with abnormal birth history were more likely to be female, of Black race or Hispanic ethnicity, to have low household income, or part of a multiple birth. Unadjusted BP measurements, baseline GFR, and change in GFR did not differ significantly between the groups; no differences were seen after adjusting for confounders by propensity score matching.Abnormal birth history does not appear to have exerted a significant influence on BP or GFR in this cohort of children with CKD. The absence of an observed association is likely secondary to the dominant effects of underlying CKD and its treatment.

Primary liver cancer (PLC) causes nearly 700,000 annual deaths worldwide predominately in Asia and sub-Saharan Africa; >370,000 deaths occur in the People's Republic of China, alone. Two factors synergistically associated with PLC are chronic infection with hepatitis B (HBV) and repetitive ingestion of aflatoxin (AFB)-contaminated foods. Utilizing information collected over several decades by the Qidong Cancer Registry, mortality rates from PLC were compared to timelines for regional implementation of HBV vaccination and levels of AFB exposure. The concentration of the AFB-lysine adduct was quantified by isotope dilution mass spectrometry in randomized, age-matched subsets of archived serum samples collected from 1989-2012. Economic, social and public health changes occurring during this time period were examined including implementation of a universal vaccination program and the adaptation of an open policy of food provisionment which led to rice replacing maize as the major dietary staple in the Qidong region. Although the crude rates of PLC increased from 1972-1990s (50/100,000 to a steady-state rate of 75/100,000), much of the increase can be attributed to a proportionate aging population. Upon stratifying by birth cohort, no significant change in mortality rate from PLC was found for individuals over 40 years of age. However, 60-75% mortality declines in 20-24, 25-29, 30-34 year olds born 1973-177 compared to similar birth cohorts of 1958-1962 were observed. The prevalence of HBV surface antigen positivity was unchanged; moreover, all these birth cohorts were born before the universal HBV vaccination of newborns. Median levels of the aflatoxin biomarker dropped from 19.3 pg/mg albumin in 1989 to non-detectable by 2009. The estimated population attributable risk of AFB-related PLC decreased from 45% in 1989 to 11% in 2012. Significant reductions in PLC mortality occurred prior to the introduction of universal hepatitis vaccination in Qidongese newborns. Agricultural and economic reforms instituted in the 1980s leading to the establishment of rice as a dietary staple was associated with a 40-fold reduction in AFB exposure. Thus, by extrapolation, changes in food-based policies altering exposure to carcinogens in the diet can have a dramatic impact on PLC mortality worldwide. Supported by NIEHS P01 ES 006052, NST China No. 2008ZX10002-015, No. 2012ZX10002-008. Citation Format: Patricia A. Egner, Jian-Guo Chen, Derek Ng, Lisa P. Jacobson, Alvaro Munoz, Jian-Hua Lu, Yuan-Rong Zhu, Geng-Sun Qian, Tao-Yang Chen, Felicia Wu, Jian-Min Wang, John D. Groopman, Thomas W. Kensler. Reduction in aflatoxin exposure drives decrease in primary liver cancer in Qidong, China. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1381. doi:10.1158/1538-7445.AM2013-1381

Epidemiological evidence has suggested that consumption of a diet rich in cruciferous vegetables reduces the risk of several types of cancers and chronic degenerative diseases. In particular, broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin (GR) which can release the chemopreventive agent, sulforaphane (SF), an inducer of glutathione transferases. Two broccoli sprout-derived beverages, one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR), were evaluated for SF bioavailability, tolerability and pharmacodynamic action. The GRR beverage relied on the conversion of GR to SF in the gut microflora whereas the SFR beverage was prepared by conversion of GR to SF with myrosinase from daikon sprouts prior to consumption. Study participants were recruited from the farming community of He Zuo Township, Qidong, People's Republic of China, previously documented to have a high incidence of hepatocellular carcinoma and more recently, exposures to substantive levels of air-borne pollutants including phenanthrene, acrolein, crotonaldehyde, benzene and ethylene oxide. Two hundred five individuals were screened at village clinics and 50 willing, healthy participants were randomized into two treatment arms. The study protocol was as follows: a 5-day run-in period, a 7-day administration of beverages, a 5-day washout period, and a 7-day administration of the opposite beverage. Bioavailability of SF, as indicated by excretion of GR, SF and SF-thiol conjugates in urine collected daily 12 hours after dosing, was measured by isotope dilution mass spectrometry. The urinary excretions of SF and its thiols were substantially greater in individuals receiving a SFR beverage compared to a GRR beverage. Determination of possible pharmacodynamic action of the SFR and GRR beverages has been assessed through measures of the urinary excretion of the mercapturic acids of acrolein, crotonaldehyde, ethylene oxide, benzene and 1,3-butadiene using liquid and gas chromatography coupled to mass spectrometry. Statistically significant increases in the levels of excretion of glutathione-derived conjugates of acrolein, crotonaldehyde, and benzene were seen in individuals receiving SFR, GRR or both compared to their pre-intervention baseline values. Increases provoked by SFR were greater than for GRR, but the differences were not significantly different. Thus, chemopreventive intervention may attenuate risks to health associated with exposures to air-borne pollutants in addition to possible effects on aflatoxin exposures in this region. Supported by NIEHS grant P01 ES006052. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-405. doi:10.1158/1538-7445.AM2011-LB-405