IGF::OT::IGF RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF MERIVA (R) AS A CANDIDATE CHEMOPREVENTION AGENT FOR GASTRIC CARCINOGENESIS

胃癌（GC）是全球第四大常见癌症和第二大癌症死亡原因1全世界大约有99万人被诊断为胃癌，其中近75%的人死于这种疾病GC也是造成最高癌症负担的原因之一，这是由丧失的残疾调整生命年决定的尽管自20世纪30年代以来胃癌发病率总体上有所下降，但预计到2030年，全球每年的癌症负担将翻一番，达到2220万例病例和1310万例死亡，其中三分之二以上的负担发生在资源有限的国家。在美国，美国癌症协会估计，2015年将诊断出24,590例新的胃癌病例，大约10,720人将死于这种类型的癌症一个人一生中患胃癌的平均风险约为1 / 111，其中男性的风险是女性的2至3倍。然而，不同国家的胃癌发病率差异很大，在欠发达国家发病率更高胃癌在东亚、南欧和东欧以及南美和中美洲更为常见，而非洲和北美的发病率最低。尽管近60%的新发胃癌病例是在亚洲诊断出来的，但与在西方国家诊断出来的病例相比，亚洲患者的预后明显更好美国和欧洲的5年胃癌生存率比日本低40%

Gastric cancer (GC) is the 4th most common incident cancer and the 2nd leading cause of cancer death worldwide.1 Approximately 990,000 people are diagnosed with GC worldwide, of whom close to 75% die from this disease.2 GC also is responsible for one of the highest cancer burdens, as determined by disability-adjusted life years lost.3 Despite the overall decrease in the incidence of GC since the 1930s, the annual global burden of cancer is projected to double by 2030 to 22.2 million incident cases and 13.1 million deaths, with over two-thirds of the burden in resource-limited nations.4, 5 In the US, the American Cancer Society estimates that in 2015 24,590 new cases of GC will be diagnosed and approximately 10,720 individuals will die from this type of cancer.6 The average risk that a person will develop GC in his/her lifetime is about 1 in 111, with the risk being 2 to 3-fold higher in men than women. However, GC incidence rates vary dramatically across different countries and are higher in less developed countries.2 GC is more common in East Asia, Southern and Eastern Europe, and South and Central America whereas the lowest incidence rates are observed in Africa and North America.7 Although nearly 60% of the new GC cases are diagnosed in Asia,8 significantly better outcomes have been reported among Asian individuals compared to those diagnosed in Western countries.9 Five-year GC survival rates are 40% lower in the US and Europe compared to Japan.10 With the high GC mortality-to-incidence ratio and the lack of routine screening methods available for asymptomatic individuals, the management of GC remains a challenge and warrants further investigations to more fully understand the biologic basis of progression and to develop chemopreventive strategies for individuals at increased risk. Curcumin is a phenolic antioxidant compound derived from the rhizome of the plant Curcuma longa. This bioflavonoid is a potent inhibitor of arachidonic acid metabolism, and blocks both lipoxygenase and cyclooxygenase activity in the intestinal mucosa. Curcumin exerts a variety of additional immunomodulatory and antioxidant effects and is thought to have broad chemopreventive potential through a variety of molecular mechanisms and cellular pathways, as recently reviewed.11 The investigators (Drs. Cruz-Correa & Morgan) from the Mayo Consortium are proposing a chemopreventive trial on a population at risk for gastric cancer (GC) using Meriva (a liposome-encapsulated formulation of curcumin) and placebo. The hypothesis is that curcumin given to individuals with gastric precancerous lesions – multifocal atrophic gastritis (MAG) & intestinal metaplasia (IM) will have a decrease in markers of inflammation including DNA damage, as compared to placebo, after six months of taking the study agent. Meriva® (Curcumin) is a patented formula of curcumin that includes a dietary phenolic with soy lecithin (non-GMO). The curcumin content and the curcuminoid absorption is 27 fold higher when compared to curcumin alone.