Nutritionl Epidemiology of Cncer in Kore RESEARCH COMMUNICATION Nutritionl Epidemiology of Cncer in Kore: Recent Accomplishments nd Future Directions He Dong Woo, Jeongseon Kim* Abstrct Becuse diet is closely relted to cncer incidence nd mortlity, recent studies in cncer epidemiology hve focused on dietry fctors. The results of studies on nutritionl cncer epidemiology in Kore re discussed in this reserch pper. Most studies hve used cse-control design focused on brest or gstric cncer ptients. Antioxidnts were ssocited with reduced risk of gstric cncer in most studies, but this ssocition ws not observed for brest cncer. Most diets consumed by Korens tht included fruits nd vegetbles were ssocited with reduced cncer risk, but high concentrtions of slt in food were positively ssocited with gstric cncer risk. Genetic susceptibility ws considered in severl studies, nd food contminnts were ssessed to estimte life-time cncer risk. Recent studies hve mde dvnces in understnding the reltionship between diet nd cncer mong Koren popultions. However, becuse the history of nutritionl cncer epidemiology in Kore is reltively short, the subjects covered nd methodology of the reserch hve been limited. A cohort design with lrge smple size nd pproprite methods to ssess subjects usul intke my be needed to determine the true ssocition between diet nd cncer in the future. Keywords: Koren - nutrition - diet - cncer - epidemiology Asin Pcific J Cncer Prev, 12, 2377-2383 Introduction Cncer is leding cuse of deth in Kore. The cncer mortlity rte ws 146.6 per 100,000 popultion in 2010, n increse of 18.7 percent from 2000 to 2010 nd 59.7 percent from 1990 to 2010 (Sttistics Kore, 2011). Dietry nd lifestyle chnges cn ffect cncer incidence nd mortlity, nd the nutritionl epidemiology of cncer hs become n importnt prt of cncer prevention. The World Cncer Reserch Fund/Americn Institute of Cncer Reserch (WCRF/AICR, 2007) specifies recommendtions for food, nutrition, physicl ctivity, nd body composition to prevent cncer, lrgely bsed on nutritionl epidemiology reserch. However, there re severl issues in the study of the nutritionl epidemiology of cncer. Mesurement errors in diet exposure, especilly ssocited with food frequency questionnires (FFQ), complicte the identifiction of n ssocition between diet nd cncer (Binghm et l., 2008; Michels, 2001). Extreme diets re rre in the generl popultion, nd ssessing diets with smll vrinces mong subjects mkes it difficult to detect ccurte ssocitions between diet nd cncer. Minor ssocitions between diet nd cncer cn be esily confounded by other lifestyle fctors. Nevertheless, the nutritionl epidemiology of cncer hs chieved notble ccomplishments. Although most types of cncers re closely relted to nutrition nd other lifestyle fctors, the history of nutritionl cncer epidemiology in Kore is reltively short. Previous studies on nutrition nd cncer hve primrily focused on the nutritionl sttus of cncer ptients, who re likely to suffer from mlnutrition. Becuse of the importnce of nutrition in cncer epidemiology nd the fct tht the Koren diet is considerbly different from the diet in western countries, studies on the ssocition between diet nd cncer risk hve recently received incresed ttention from Koren reserchers. Koren diets re rich in fruits nd vegetbles, which hve n inverse ssocition with cncer risk, but the vegetbles re generlly consumed s pickled vegetbles mixed with vrious condiments, which tend to hve high sodium content. Cooking methods tht vry bsed on culturl differences re considered n importnt prt of the nutritionl epidemiology of cncer. This study ims to summrize previous reported results nd discuss future spects of the nutritionl epidemiology of cncer for Koren popultions. Mterils nd Methods Vrious keywords, including Koren, Kore, food, diet, intke, nutrition, cncer, nd risk, were used to serch for studies on the nutritionl spects of cncer risk mong Koren popultions on PubMed (http:// www.ncbi.nlm.nih.gov/pubmed/), KoreMed (http:// Cncer Epidemiology Brnch, Ntionl Cncer Center, Goyng-si, Kore *For correspondence: jskim@ncc.re.kr Asin Pcific Journl of Cncer Prevention, Vol 12, 2011 2377
He Dong Woo nd Jeongseon Kim Tble 1. Summry OR/RR of Nutrient Intke for Different Cncer Sites Results Tble 2. Summry OR/RR of Food Intke for Different Cncer Sites Sttisticlly significnt results; b Non-significnt resultsreference list: Lee et l., 2003, Lee et l., 2003b, Cho et l., 2010, Do et l., 2007, Hong et l., 2008, Kim et l., 2002, Kim et l., 2003, Kim et l., 2008, Kim et l., 2009b, Lee et l., 2002, Lee et l., 2003, Lee et l., 2003b, Lee et l., 2004, Nn et l., 2005, Prk et l., 2000, Shin et l., 2010, Yng et l., 2010b, Yu et l., 2010, Yun et l., 2010, Zhng et l., 2009 Asin Pcific Journl of Cncer Prevention, Vol 12, 2011 2378 Brest Gstric Brest Gstric Cervix Energy 1.04 1.35 1.13 Crbohydrte 1.59 1.24 1.37 Crbohydrte_GI 0.44 Crbohydrte_GL 0.85 Protein 0.6 0.61 Protein_niml 0.63 Protein_vegetble 0.39 Protein_soy 0.51 Ft 1.15 0.62 0.67 Ft_niml 0.93 Ft_vegetble 0.49 Ftty cid 1.02, 1.65 0.55-0.75 Ftty cid 0.44-0.50 Fiber 0.37 Sttisticlly significnt results; b Non-significnt results; Reference list: Do et l., 2003, Kim et l., 2005, 2008, 2009b, 2010, Yun et l., 2010 koremed.org/serchbsic.php), nd KMBse (http:// kmbse.medric.or.kr/). Vrious micro- nd mcronutrients, foods, nd contminnts in food were exmined s risk fctors for cncer. Severl studies were included on the genetic influence in the ssocition between nutrition nd cncer risk. Mcronutrients nd food intkes Crbohydrte, protein nd ft intke, s well s totl energy intke, hve not been ssocited with cncer risk (Do et l., 2003; Kim et l., 2005; Kim et l., 2010). However, protein or ft from vegetble sources hve been found to reduce the risk of gstric cncer (Kim et l., 2005) (Tble 1). Fruits nd vegetbles, which hve been widely studied, hve been inversely ssocited with cncer risk, wheres pickled vegetbles significntly incresed brest nd gstric cncer risk (Tble 2). Mushroom intke hs been ssocited with reduced cncer risk (Kim et l., 2002; Lee et l., 2004; Hong et l., 2008; Shin et l., 2010), but one study reported n ssocition with significnt increse in brest cncer risk (Lee et l., 2003). It seems tht the selection of cses in this study ws not restricted to newly dignosed cncer ptients; mushrooms re frequently consumed by cncer ptients becuse mushrooms re considered by Koren cncer ptients to be beneficil food for brest cncer. Intkes of mets, especilly chrcol grilled mets, nd eggs hve been found to increse cncer risk (Lee et l., 2003; Kim et l., 2002). The results of soyben intke hve been inconsistent. Soyben curd, fermented soy nd soyben milk reduced cncer risk (Prk et l., 2000; Kim et l., 2002; 2008; Lee et l., 2002; 2003b; Cho et l., 2010), wheres soyben pste nd soyben pste stew incresed gstric cncer risk (Prk et l., 2000; Nn et l., 2005; Zhng et l., 2009). Fish intke showed n Brest Gstric Colon Brest Gstric Colon Fruits 0.7 0.20, 0.30 0.74-1.00 Fruit juice 0.4 0.55-0.83 0.55 Vegetbles 0.22 0.76 0.8 Fresh vegetbles 0.09 0.2 0.92 Green vegetbles 0.3 0.24 0.6 Light-colored vegetbles 0.3 1.1 Sesoned rw vegetbles 0.20, 0.30 Pickled vegetbles 2.47 1.57-4.10 Kimchi_cbbge 0.83 0.5 Kimchi_rdish 1.96 0.77 1.78 Mushroom 0.40-1.50 0.3 Mets 0.40-1.70 1.72 0.94, 1.67 Met_chrcol grilled 2.11 1.58 Eggs 1.6 0.71 Soybens 0.36, 0.67 0.57 0.70-1.41 0.85 1.11 Soyben curd 0.37, 0.45 0.30-0.51 0.71 Soyben pste 1.62, 1.63 Fermented soy 0.31 0.72, 0.76 Soyben milk 0.5 Soyben pste stew 2.73 Fish 0.55, 1.50 0.43 Slt-fermented fish 2.4 2.1 Other sefood 0.13, 0.66 0.7 Seweed 0 43 0.41, 0.52 0.70, 0 89 0.78 White rice 1.51 Boiled rice with ssorted mixture 0.42 0.26 0.97 1.7 Cerels 1.8
inverse ssocition with cncer risk, but slt-fermented fish incresed the risk of gstric cncer (Lee et l., 2002; Lee et l., 2003b). These results suggest tht typicl Koren diets re generlly ssocited with reduced cncer risk. However, high concentrtions of slt in food re mjor problem in Koren diets nd, re ssocited with n incresed incidence of gstric cncer. Becuse foods re not consumed in isoltion, the ssocition between single food nd cncer risk cnnot be ssessed ccurtely. Therefore, nlyses of dietry ptterns re necessry to ssess the interctions between food components in the nutritionl epidemiology of Cncer. The vegetble-sefood pttern nd the wellbeing diet pttern hve been ssocited with reduced risk of brest cncer (Tble 5). Incresed risks of cncer hve been identified in the pork nd lcohol nd coffee nd cke ptterns. Consistent with the results for slted Nutritionl Epidemiology of Cncer in Kore food items, slt preference hs been ssocited with incresed gstric cncer risk (Be et l., 2001; Kim et l., 2010b). A preference for well-done met nd broiled food consumption incresed the risk of gstric cncer (Be et l., 2001; Zhng et l., 2009). Micronutrients The effects of dietry ntioxidnt intke on cncer risk hve been extensively studied mong Koren popultions (Tble 3). Antioxidnts, minly vitmins, were ssocited with reduced risk of cncer, but numerous studies hve filed to show sttisticlly significnt results. Dietry ntioxidnt intkes from food were inversely ssocited with the risk of gstric cncer, but not brest cncer. High consumption of vitmins A, B1, B2, E, β-crotene (Kim et l., 2005), B6 (Kim et l., 2005; Zhng et l., 2009) nd folic cid (Kim et l., 2005, Kim et l., 2009) hve Tble 3. Summry OR/RR of Dietry Intke nd Serum Concentrtions of Antioxidnts for Different Cncer Sites Brest Gstric Gynecologic Brest Gstric Gyneclogic Dietry intke Vitmin A 0.36 0.36 0.72-1.03 Retinol 0.62-0.88 0.57 0.81 Vitmin B1 0.42 0.79, 2.77 Vitmin B2 0.37 0.47, 0.68 Vitmin B3 1.84 0.6 Vitmin B6 0.35, 0.71 Folic cid 0.4 0.82, 0.83 0.92 Vitmin B12 0.94 Vitmin C 0.37 0.36 0.76, 1.07 0.55, 0.79 Vitmin E 0.22, 0.49 0.48 0.81 0.58 β-crotene 0.42 0.35 0.48 0.8 Isoflvones 0.81 Dietry & supplement Vitmin A 0.63 0.37 0.35 Vitmin B1 0.41 0.72 Vitmin B2 0.42 1.32 Vitmin C 0.35 0.35 0.7 Vitmin E 0.47 0.53 0.67 Serum concentrtions Vitmin A 0.5 Retinol 0.74 Vitmin B1 0.6 Vitmin B2 0.5 Vitmin B3 0.7 Vitmin B6 0.5 Folic cid 0.5 0.45 Vitmin B12 0.29 Vitmin C 0.4 α-tocopherol 0.3 0.19 0.32 γ-tocopherol 0.18 Lycopene 0.15, 0.16 1.03 Zexnthin+lutein 0.14 0.33 α-crotene 0.37 β-crotene 0.08 0.10, 0.12 Cryptoxnthin 1.31 Genistein 0.54 Didzein 0.21 Equol 0.5 Enterolctone 0.87 Sttisticlly significnt results; b Non-significnt results; Reference list: Cho et l., 2009, Cho et l., 2010, Do et l., 2003, Jeong et l., 2009, Kim et l., 2002b, Kim et l., 2005, Kim et l., 2009, Kim et l., 2010, Ko et l., 2009b, Lee et l., 2008, Lee et l., 2008b, Lee et l., 2010, Lee et l., 2011, Zhng et l., 2009 Asin Pcific Journl of Cncer Prevention, Vol 12, 2011 2379
He Dong Woo nd Jeongseon Kim Tble 4. Summry OR/RR of Dietry Minerl Intke for Different Cncer Sites 2380 Brest Gstric Brest Gstric Clcium 0.33 0.43 Iron 0.76 0.49, 0.77 Phosphorous 0.38 0.98 Potssium 0.36 0.64 Selenium 0.98 Sodium 2.14 0.56 Zinc 0.51 Sttisticlly significnt results; b Non-significnt results; Reference list: Kim et l., 2005, Lee et l., 2008, Zhng et l., 2009 been ssocited with reduced risk of gstric cncer compred to low consumption groups, but the effects of vitmin A, retinol (Lee et l., 2011; Do et l., 2003; Lee et l., 2008), vitmins B1 nd B2 (Do et l., 2003; Lee et l., 2008), vitmin B3 (Lee et l., 2008), folic cid, vitmin C, β-crotene (Lee et l., 2008; 2011), vitmin E (Do et l., 2003), nd isoflvones (Cho et l., 2010) showed no sttisticlly significnt results. Although few studies hve ssessed ntioxidnt intkes from both food nd supplements or serum concentrtions, ntioxidnts significntly reduced cncer risk, except for brest cncer, in most studies. The results were not sttisticlly significnt in mny studies ssessing only dietry intke of ntioxidnts. Therefore, the ssessment of ntioxidnt concentrtions using serum specimens or the inclusion of supplement use in dietry intke might contribute to the identifiction of n ssocition between ntioxidnts nd cncer risk. Overll, the results showed tht dietry intke or serum concentrtion of ntioxidnts decresed gstric cncer risk, but brest cncer showed little ssocition with ntioxidnt intke. The effects of minerl intke on cncer risk were similr to the results for ntioxidnts (Tble 4). Intke of most minerls ws ssocited with reduced risk of gstric cncer, but not brest cncer. High intke of clcium, phosphorous, nd potssium reduced gstric cncer risk (Kim et l., 2005), but there ws no significnt ssocition between iron intke nd either gstric or brest cncer risk. Sodium, which is consumed in lrge mounts in Kore, Tble 5. Summry OR/RR of Dietry Pttern nd Hbit for Different Cncer Sites Asin Pcific Journl of Cncer Prevention, Vol 12, 2011 ws positively ssocited with gstric cncer risk (Zhng et l., 2009) Gene-diet interctions Diet lone cn influence the etiology of cncer, but its effect cn differ ccording to genetic susceptibility. Becuse diet cn ffect the ssocition between genetics nd cncer risk, gene-diet interctions hve become n importnt prt of the study of cncer etiology. Atxi telngiectsi mutted (ATM) diplotype hs been ssocited with brest cncer in women with low intke of ntioxidnt vitmins bsed on recessive model. However, this ssocition ws not observed in the high intke group, suggesting tht the effect of ATM diplotype on brest cncer risk could be modified by intkes of ntioxidnt vitmins (Lee et l., 2010). The p53 muttion did not ffect the ssocition between ntioxidnt vitmin intke nd brest cncer risk (Kim et l., 2002b). A C677T bse chnge in methylenetetrhydrofolte reductse (MTHFR) gene, n enzyme of folte metbolism, ws ssocited with reduced enzyme ctivity, resulting in mild increse in plsm homocysteine. Women with the MTHFR TT genotype in the low green vegetble intke group showed incresed brest cncer risk compred to women with the CC/CT genotype. Brest cncer risk did not increse significntly in the high green vegetble consumption group for women with the TT genotype (Lee et l., 2004). People with low consumption of soybens with risk gene vrints of IL10, n nti-inflmmtory cytokine, hd n incresed risk of gstric cncer compred to people with high consumption of soybens nd no risk gene vrints (Ko et l., 2009). N-Acetyltrnsferse (NAT), which is key enzyme in the ctivtion nd detoxifiction of chemicl crcinogens, cted s n importnt modifier of the doneness of met on gstric cncer risk. People with preference for well-done met hd higher risk of gstric cncer. This ssocition incresed, mong people with slow/intermedite cetyltors, nd the ssocition ws not observed in people with rpid cetyltors (Zhng et l., 2009). The hogg1 gene is involved in the removl of 8oxoG dducts, the DNA lesions induced by rective oxygen species. Thus, Brest Gstric Colon Brest Gstric Colon Vegetble-sefood 0.14 Well-being diet 0.16 Met-strch 0.69 Met & fish 0.55 Pork & lcohol 1.92 Milk & juice 0.4 Rice & kimchi 1.22 Coffee & cke 2.18 Animl food preference 1.01 Slt preference 1.10, 9.80 Well-done met preference 1.24 Frequent broiled food consumption 3.33 Mel regulrity 1.04 Sttisticlly significnt results; b Non-significnt results; Reference list: Be et l., 2001, Cho et l., 2010b, Kim et l., 2010b, Oh et l., 2004, Zhng et l., 2009, Kim et l., 2010b
the Ser326Cys polymorphism of hogg1 might hve different effects on the ssocition between dietry fctors nd cncer risk. Met intke ws not ssocited with incresed colon cncer risk in Ser/Ser or Ser/Cys crriers, but frequent consumption of met incresed the risk for colon cncer in Cys/Cys crriers. However, polymorphism of the hogg1 gene did not ffect other dietry fctors, such s vegetbles nd soybens (Kim et l., 2003). Chemicls in food Vrious chemicls hve been introduced into the body by environmentl contminnts in food nd food preservtives. Becuse of increses in environmentl pollutnts nd processed food intke, people re exposed to numerous hzrdous chemicls. Thus, the contminnts in food tht hve dverse helth effects hve become public helth concern. Severl contminnts in the Koren diet hve been investigted, nd their effects on cncer risk hve been ssessed. Nitrtes re nturlly present in humn diets, but high levels of nitrte concentrtions led to high concentrtions of nitrites, which form potent crcinogenic N-nitroso compounds. Nitrte intke from food hs not been ssocited with brest or gstric cncer risk, but higher rtio of nitrtes to folte intke hs been found to increse both brest nd gstric cncer risk. Furthermore, the nitrte/vitmin E rtio hs been ssocited with gstric cncer risk, suggesting tht the vilbility of ntioxidnt vitmins, such s folte nd vitmin E, might moderte the hrmful effects of nitrtes on cncer risk (Yng et l., 2010; Kim et l., 2007). The polycyclic romtic hydrocrbons (PAHs) cn be found in vrious food items, such s grilled met, vegetbles, sefood nd oils. Benzo[]pyrene (BP), member of the PAH clss, is used s surrogte mrker for PAH contmintion. Humns re exposed to BP primrily through dietry intke, nd the detectble levels of BP cn differ by cooking procedures. Pyrolytic formtion by cooking method nd the estimted dietry intke of BP hs been nlyzed. High concentrtions of BP were detected in fried chicken nd smoked dried beef, nd low concentrtions were detected in nonmet food items (Lee nd Shim, 2007). BP ws not detected in rw foods, but higher concentrtions were formed by broiling food (Choi nd Lee, 1994). The estimted dietry BP-relted cncer risk ws 1.52 10-5, nd the lifetime cncer risk of eting cooked foods ws estimted to be 1.77 10-6 for broiled foods nd 1.65 10-7 for boiled foods (Choi nd Lee, 1994; Lee nd Shim, 2007). Sixteen PAHs from commonly consumed sefood in Kore were mesured, nd the lifetime cncer risk ws estimted to be 2.85 10-6 (Moon et l., 2010). Nutritionl sttus of cncer ptients Mlnutrition is common problem mong cncer ptients. Severe mlnutrition is often responsible for the deth of cncer ptients, nd well-nourished cncer ptients hd better prognoses. Vrious methodologies hve been used to ssess the nutritionl sttus of cncer ptients in Koren popultions. Among oncology outptients receiving chemotherpy, ptients with gstrointestinl cncer hd 50% likelihood nutritionl risk, wheres Nutritionl Epidemiology of Cncer in Kore only 6.3% of brest cncer ptients without orl intke difficulties were t nutritionl risk (Kim et l., 2008b). Gstric cncer ptients who hd undergone gstrorectomy were t higher risk for mlnutrition (Sohn, 2010), but the nutritionl sttus of gstric cncer ptients returned to pre-surgicl sttus 12 months fter surgery (Ryu nd Kim, 2010). Mlnutrition ws negtively correlted with the survivl time of metsttic cncer ptients (Choi et l., 2006), nd ptients t dvnced stges of cncer hd significnt nutritionl deficiencies (Wie et l., 2009). Discussion Studies of the nutritionl epidemiology of cncer mong Koren popultions hve usully been performed using cse-control design. However, cse-control studies of diet re vulnerble to selection nd recll bises, which my produce misleding results. Two cohort studies hve been conducted to determine the ssocition between dietry preference nd cncer risk (Yun et l., 2008; Kim et l., 2010b), but the cohorts used in the studies were not specificlly designed for the reserch. These studies used dietry dt obtined from regulr helth exmintion of Koren government employees nd the Koren Centrl Cncer Registry to identify the incidence of cncer. Thus, the dietry informtion ws limited to few questions bout dietry hbits nd preferences. Two nested csecontrol studies were conducted to exmine the ssocition between diet nd gstric cncer risk, using subjects from the Koren Multicenter Cncer Cohort (KMCC). The KMCC, community-bsed prospective cohort, ws strted in 1993 for genomic epidemiologicl studies on cncer etiology (Yoo et l., 2002). A self-dministered FFQ with 4 frequency ctegories nd 3 portion sizes hs been collected since 1995. A nested cse-control study using this FFQ dt showed n ssocition between diet nd cncer, indicting tht the ssocition between IL10 genetic polymorphisms nd the risk of gstric cncer ws modified by soyben product intke (Ko et l., 2009). Severl other genomic cohorts in Kore, such s the Koren Ntionl Cncer Center Cohort (KNCCC), the Koren Helth Exminees Cohort (KOEX), the Koren Helth nd Genome Epidemiology Study (KHGES), nd Koren Hydro-Nucler Power (KHNP) hve included dietry informtion, but no studies using this dietry informtion hve been reported. Cohort studies re less susceptible to bis thn cse-control studies, but the timing of dietry dt collection is importnt. Dietry intke hs usully been ssessed using dt collected t the bseline of the cohort, but this is insufficient for ssessing longterm exposure. Thus, dietry informtion should be updted regulrly nd consistently. The follow-up time for the cohorts in Kore ws reltively short, nd the smple size ws limited. Furthermore, these cohorts hve not focused primrily on the effects of diet on helth. Lrge cohorts with vlid nd ccurte dietry ssessment methods, such s Europen Prospective Investigtion into Cncer nd Nutrition (EPIC), re needed for future reserch on the nutritionl epidemiology of cncer. The ssocition between dietry fctors nd cncer risk hs been inconsistent. It is difficult Asin Pcific Journl of Cncer Prevention, Vol 12, 2011 2381
He Dong Woo nd Jeongseon Kim to ccurtely ssess individul nutritionl sttus, nd errors in the mesurement of dietry intke in epidemiologicl studies often led to bised findings. The FFQ, which is frequently used in epidemiologicl studies, introduces both systemic nd rndom error. Despite its crude ssessment, the FFQ is believed to be ble to ccurtely detect n ssocition between diet nd cncer risk (Michels, 2005; Schtzkin et l., 2009). However, minor ssocitions between dietry fctors nd cncer risk cn esily be compromised by mesurement errors. The ssessment of plsm concentrtion levels in individul diets will be useful in the future study of the nutritionl epidemiology of cncer. Ongoing cohort studies hve mostly collected biospecimens. The vilbility of both dietry ssessments nd biospecimens for gene expression dt fcilitte nutrigenomics, the study of nutritionl influence on gene expression. Our recent reserch hs shown tht high intke of soy isoflvones my be ssocited with incresed risk of cncer recurrence in HER2-positive brest cncer ptients, but not in HER2-negtive ptients (Woo et l., 2012). Thus, the sme diet cn hve different effects on the risk of cncer incidence nd cncer survivl. Gene-diet interction dt hve been reported in Kore, but bioctive food constituents cn influence multiple processes of crcinogenesis. Therefore, nutrigenomics, cn suggest personlized, optiml nutrition (WCRF/ AICR, 2007). Suitble biomrkers t resonble costs should be mde vilble, nd technologicl methods re References Be JI, Song YM, Yoo JH (2001). A hospitl bsed cse control study on the risk fctors of stomch cncer. J Koren Acd Fm Med, 22, 539-547. Binghm S, Luben R, Welch A, et l (2008). Associtions between dietry methods nd biomrkers, nd between fruits nd vegetbles nd risk of ischemic hert disese, in the EPIC Norfolk Cohort Study. Int J Epidemiol, 37, 978 87. Cho H, Kim MK, Lee JK, et l (2009). 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