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Although the protective effects of physical activity against several cancers are well established, evidence is inconsistent concerning Asian populations. Therefore, we assessed the association between the characteristics of physical activity and overall and type-specific cancer incidence in Koreans and examined the differences in association according to obesity status. Using prospective data from 112,108 participants in the Health Examinees study-G from 2004 to 2013, we evaluated the association between leisure-time physical activity (LTPA) and the incidence of overall and type-specific cancers using the Cox proportional hazards model. Self-reported LTPA participation, duration per week, intensity, type, and diversity were assessed. The incidence of overall and type-specific cancers, including colorectal, gastric, lung, breast, and prostate cancer and 13 obesity-related cancers, was identified using the Korea Central Cancer Registry from 1999 to 2018. Analyses were also stratified according to obesity status. In overweight males, participation in vigorous LTPA (hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.72–0.97) and walking (HR: 0.84, 95% CI: 0.72–0.98) were associated with a lower risk of cancer overall. Regarding cancer types, climbing was marginally associated with a lower risk of colorectal cancer in overweight males (HR: 0.61, 95% CI: 0.37–1.00). In normal-weight females, although there was an increased risk in those performing recreational activities, this risk was attenuated when those diagnosed with thyroid cancer were excluded. In the analysis for 13 obesity-related cancers, consistent associations were found. These findings suggest the need for greater public awareness regarding physical activity among overweight individuals within the Asian population.

Background: Previous studies have suggested the disturbance in the microbial composition followed by dysbiosis contribute to the onset of gastrointestinal malignancies, including colorectal cancer (CRC). However, the impact of microbiome on short-term postoperative complications after CRC surgery is not well investigated. This study aimed to investigate whether the gut microbial diversity and composition in CRC patients were associated with the occurrence of short-term postoperative complications. Methods: We linked the clinical data and preoperative sequencing data of fecal samples of 331 patients who underwent CRC surgery from 2017 to 2019 in Seoul National University Hospital. Short-term postoperative complications were defined as first complications that developed within 30 days of surgery. We used linear discriminant analysis (LDA) of effect size (LEfSe) in the Galaxy webserver to identify enriched bacteria in patients with and without complications. Then, we calculated microbial dysbiosis index (MDI) by each patient and compared them according to the complication status. Wilcoxon rank sum test was conducted to compare the alpha diversity indices according to the complication event. Subgroup analyses according to types of complications were also performed: surgical procedure-related (SP) group and nonsurgical procedure-related (NSP) group. Results: Overall, 84 patients (25%) developed short-term postoperative complications: SP group (n=39) and NSP group (n=45). From the LEfSe analysis, Bacteroides uniformis (LDA score: 3.64, p-value 0.04) and Clostridium colicanis (LDA score: 3.39, p-value 0.01) were enriched in patients who developed short-term complications, whereas Roseburia faecis (LDA score: 3.26, p-value 0.05), Bifidobacterium bifidum (LDA score: 2.98, p-value 0.03), Faecalibacterium sp. (LDA score: 3.12, p-value 0.02) and Prevotella nigrescens (LDA score: 2.87, p-value 0.05) were enriched in patients without complications. When compared with patients without complications, taxa related to class Gammaproteobacteria, genus Clostridium, species Roseburia faecis, and Desulfovibrio D168 were abundant in the SP group. Alpha diversity indices were not significantly different according to the complication status or the type of complication. MDI from the enriched bacteria were significantly higher in patients with complications compared to those without complications (p-value Conclusion: Our study suggests a potential relationship between microbial composition and surgical outcome in CRC patients. No significant difference in alpha diversity was observed according to the occurrence or the type of complication. Further studies are needed to investigate the postoperative changes of microbial features. Citation Format: Hyeree Park, Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Aesun Shin. Microbial diversity and composition according to short-term postoperative complication status in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5892.

Background: Gut microbiota has been introduced to involve in the migration and invasion stage of metastasis of colorectal cancer (CRC) cells and interact with both the pharmacokinetics and pharmacodynamics of chemotherapeutic agents and immune checkpoint inhibitors. In this study, we examined microbiome features in association with all-cause mortality of CRC patients and examined their interactions with clinical factors. Methods: We performed 16S rRNA sequencing for 331 preoperative fecal samples of CRC patients at Seoul National University Hospital, Korea. Multiple Cox proportional hazard model was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause mortality due to microbiome features (within-sample diversity indices, species patterns, genus abundance, and taxonomic co-occurrence networks) and clinical factors (tumor grade and stage, surgical methods, neoadjuvant and adjuvant therapies, and invasion). We added the multiplicative term into the model to test the interaction between gut microbiota and clinical characteristics. Results: During a median follow-up of 3.7 years, deaths from any causes were reported in 46 patients. From 172 species, the principal component analysis identified 4 patterns, which explained a total 66.1% variation in species abundance. Of 77 genera, 9 co-occurrence networks were identified by the SParse InversE Covariance Estimation for Ecological Association Inference. For genus level, the risk of death was positively associated with Butyricicoccus (HR=1.54, 95% CI=1.17-2.04), but inversely associated with Lactococcus (HR=0.60, 95% CI=0.37-0.95), Acidaminococcus (HR=0.57, 95% CI=0.34-0.96), Megasphaera (HR=0.79, 95% CI=0.64-0.99), Mitsuokella (HR=0.75, 95% CI=0.57-0.99). All-cause mortality was associated with well or moderately differentiated adenocarcinoma (HR=3.84, 95% CI=1.83-8.07), neoadjuvant therapy (HR=4.10, 95% CI=1.40-12.0), tumor stage IV (HR=8.64, 95% CI=3.42-21.8), and presence of venous invasion (HR=2.32, 95% CI=1.08-4.97). Among clinical pathological factors associated with all-cause mortality, Bacteroides abundance significantly interacted with both tumor stage (pinteraction=0.013) and venous invasion (pinteraction=0.001). Conclusion: Our study identified several microbiome features in links with either increasing or decreasing mortality from any causes. Interactions between the gut microbiome and clinical factors might inform insights on how the gut microbiota modulates the effect of clinical factors on CRC prognosis after the curative operation. Further research using postoperative information is needed to confirm our findings. Citation Format: Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Aesun Shin. Gut microbiome interacts with clinical characteristics on all-cause mortality of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2364.

Introduction: Lifetime estrogen exposure is an essential factor for breast carcinogenesis. While adiposity impacts circulating hormones throughout a woman's life, weight gain in adulthood appears to have paradoxical effects at premenopausal and postmenopausal breast cancer risk. Thus, we evaluated the association between weight change throughout distinct lifetime periods with breast cancer risk stratified by menopausal status. Methods: We conducted a prospective cohort study of 73,347 Korean women aged 40 to 69 years who were enrolled in the population-based Health Examines-Gem Study (HEXA, 2004-2013). Using anthropometry obtained from physical examination and self-reported weights at ages 18-20, 35 and 50 assessed through a validated questionnaire at enrollment, we calculated body mass index (BMI), absolute weight change and weight change per year for the following 5 age periods: entire adulthood (age 18-20 years to recruitment); early reproductive years (age 18-20 to age 35); middle adulthood (age 35 years to recruitment); late reproductive years (age 35 to 50); and peri-/postmenopausal years (since 50 years to recruitment). Restricted cubic spline model was constructed using three knots and Cox regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer risk. Results: We identified 843 breast cancer cases over 758,116 person-years of follow-up (median 9.2 years). Postmenopausal women with BMI over 27.5kg/m2 at enrollment had a 48% (aHR 1.48, 95%CI 1.13-1.96; p-trend=0.03) increased risk of breast cancer. Women who gained 5 kg or more since age 35 had a 66% increased risk of premenopausal breast cancer (aHR 1.66, 95%CI 1.21-2.28; p-trend=0.03) compared to those who had stable weight (±2.5 kg), while those who gained 0.75 kg annually after the age of 50 had a 40% increased risk of postmenopausal breast cancer (aHR 1.41, 95%CI 1.01-1.96; p-trend=0.03). There was a non-linear relationship between annual average weight change in entire and middle adulthood and breast cancer risk (p < 0.01). The results remained unchanged after further adjusting for weight at each age. Conclusions: Our findings suggest that absolute weight gain from age 35 was associated with an increased risk of premenopausal breast cancer, while persistent weight gain from age 50 increased the risk of breast cancer in postmenopausal women. Furthermore, we confirmed that adiposity, assessed as body mass index, increases the risk of postmenopausal breast cancer in Korean women. Citation Format: Katherine De la Torre, Woo-Kyoung Shin, Hwi-Won Lee, Dan Huang, Sukhong Min, Aesun Shin, Jong-Koo Lee, Wonshik Han, Daehee Kang. Weight gain after age 35 increases the risk of breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3051.

Background: One of the major topics about colorectal cancer (CRC) is the core role of various immune cells against cancer cells. To comprehensively understand genetic basis of immune system underlying CRC progression, association of single-nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of immune-related genes were investigated with colorectal cancer survival. Methods: CRC patients enrolled in the Seoul National University Hospital with prospective follow-up were included in the study. From blood-derived DNA from CRC patients, genome-wide SNPs were genotyped by using the Korea Biobank Array (KoreanChip). 2,729 immune-related genes were selected from Ensembl, Gene Ontology (GO), and KEGG database and 37,398 mapped SNPs were extracted. SNP or PRS-based Cox proportional hazard models were fit for events of overall survival (OS) and progression-free survival (PFS) estimating effect sizes with hazard ratios (HRs). PRS was calculated as effect size weighted sum of risk alleles of individual patients and categorized into tertiles. To investigate enriched pathways, protein-protein interaction networks analysis was conducted. Bonferroni-corrected p-value (1.3 × 10−6) was used as statistically significance threshold. Results: Among 960 CRC patients, 154 (16.0%) occurred events of death and 245 (25.5%) of progression during the follow-up (median=1,698 days, range=7-2,563 days). For OS, a statistically significant associations were mapped to ACTR3B, ST6GAL1, COTL1, PRKCZ, and CAMK1D genes with the strongest SNP rs14808985 (HR=3.07, P=1.87 × 10−7). For PFS, marginal association was mapped to MECOM gene with the strongest SNP rs16854234 (HR=1.48, P=6.13 × 10−6). In PRS analysis, the highest tertile group showed the prominently increased risk for OS (HR=25.0, P Conclusions: We identified novel predictive biomarker genetic variants in ACTR3B and MECOM genes associated with OS and PFS, respectively, among CRC patients. Additionally, we presented PRS as a useful biomarker for survival outcomes and suggested enriched biological pathways involved in CRC progression. These knowledges can promote the understanding of CRC survival and the development of immune-related therapeutic interventions for CRC patients in the future. Citation Format: Dabin Yun, Nan Song, Jin-Ah Sim, Min Jung Kim, Ji Won Park, Seung Yong Jeong, Aesun Shin. Novel predictive biomarker SNPs and polygenic risk scores of immune-related genes for colorectal cancer survival in Korea. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5234.

Background: The association between excessive sugar intake and the risk of breast cancer has been considered in epidemiologic studied, however, the results are unclear. This study examined to evaluated between high-sugar food intake and breast cancer in a prospective cohort study. Methods: This prospective cohort study included a total of 71,266 women aged 40-69 years from the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis was retrieved from the Korea Central Cancer Registry until 31 December 2018. Multivariate hazard ratios (HRs) and 95% of confidence intervals (CIs) for the risk of gastric cancer according to the consumption of high-sugar food were estimated using Cox proportional hazards models with age as the time scale. Results: A total of 713 incident cases of breast cancer occurred over an average follow-up period of 9.20 years. The top food contributing to total sugar intake was fruit (42.89%). We found that increased consumption of sugary cereal was associated with increased risk of breast cancer; HR for sugary cereal consumption of more than one servings/two months vs. almost never consumed was 1.34 (95% CI: 1.08, 1.65; p for trend = 0.01). Also, consumption of loaf bread (p for trend = 0.03), ice cream (HR for ice cream consumption of more than one servings/week vs. almost never consumed = 1.26; 95% CI: 1.00, 1.58; p for trend = 0.03), and added sugar food (HR for all sugary food groups consumption of more than two servings/week vs. less than one serving/month consumed =1.28; 95% CI: 1.02, 1.61; p for trend = 0.05) was associated with increased risk of breast cancer. Conclusion: Our results suggest that a high-sugar food consumption was associated with an increased risk of breast cancer among Korean women. Key words: Sugar, High-sugar foods, Breast cancer, the Health Examinees (HEXA) study, prospective cohort study. Citation Format: Woo-Kyoung Shin, Dan Huang, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-koo Lee, Wonshik Han, Jung Eun Lee, Daehee Kang. High sugar food consumption and breast cancer risk in a prospective cohort study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4242.

Background: Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. This study aims to assess the association between reproductive factors with lung cancer incidence and mortality among Asian women. Methods: A total of 308,949 female participants with a mean age of 55.13 from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) in the Asia Cohort Consortium (ACC) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). Results: A total of 3,119 primary lung cancer cases and 2,247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70 - 0.96) and 0.78 (95% CI = 0.65 - 0.94). Corresponding HRs were lowest among women with 1-2 children, with HRs of 0.78 (95% CI = 0.66 - 0.93) and 0.72 (95% CI = 0.59 - 0.87) for lung cancer incidence and mortality. The protective association of parity and lung cancer incidence was greater among ever-smokers (HR=0.66, 95% CI = 0.49 - 0.87) than in never-smokers (HR=0.90, 95% CI = 0.74 - 1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Compared with age at menopause Conclusions: Distinct from Western women, Asian parous women, especially those who have 1-2 children had a lower risk of lung cancer incidence and mortality compared with nulliparous women. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time. Citation Format: Xin Yin, Rie Kishida, Sarah Krull Abe, Md. Rashedul Islam, Md. Shafiur Rahman, Eiko Saito, Qing Lan, Batel Bletcher, Melissa Merritt, Ji-Yeob Choi, Aesun Shin, Ryoko Katagiri, Xiao-Ou Shu, Norie Sawada, Akiko Tamakoshi, Woon-Puay Koh, Ichiro Tsuji, Chisato Nagata, Sue K. Park, Sun-Seog Kweon, Yu-Tang Gao, Shoichiro Tsugane, Takashi Kimura, Jian-Min Yuan, Yukai Lu, Seiki Kanemura, Yumi Sugawara, Keiko Wada, Min-Ho Shin, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, Keitaro Matsuo, You-Lin Qiao, Nathaniel Rothman, Wei Zheng, Manami Inoue, Daehee Kang, Wei Jie Seow. Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia Cohort Consortium. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4200.

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10–8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08–1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10–3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10−8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10−8; rs62558833, P = 7.5 × 10−8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.

Background: Previous study have indicated an association of microbial dysbiosis with stages of colorectal cancer (CRC). Meanwhile, higher microbial stochasticity has been introduced as the Anna Karenina principle (AKP) effect, which originates from the opening line of Leo Tolstoy and is translated in the microbiome as “all healthy microbiomes are similar; each dysbiotic microbiome is dysbiotic in its own way”. Here, we aim to elucidate the effect of modifiable factors on microbiome stochasticity related to dysbiosis in CRC. Methods: Fecal samples from 331 CRC patients, were collected prior to their surgery at Seoul National University Hospital. Bacteria that were enriched in early- and late-stage CRC groups were identified by linear discrimination analysis effect size (LEfSE) method, which was then used to calculate microbial dysbiosis index (MDI). The association of dietary choices with microbiome variability was addressed using the LEfSE analysis. The difference of intra-sample similarity index among lifestyle factors and metabolic diseases was tested to examine the AKP effect. A tree-based analysis of food choices was constructed. We then applied Procrustes framework to analyze the shape of dietary diversity and microbiome. Results: The LEfSE identified Leuconostoc, Oxalobacter, Acidaminococcus, and Methanobrevibacter were enriched in early-stage CRC, whereas Bacteroides, Fusobacterium, Lachnoanaerobaculum, Clostridium, and Granulicatella were enriched in late-stage CRC patients. The MDI derived from these bacteria had 64.2% predictive ability for CRC stages, with sensitivity and specificity of 61% and 69%, respectively. The AKP effect was found for history of smoking, alcohol consumption, and diabetes, whereas obesity and hypertension showed anti-AKP effect. For dietary choices, the hierarchical tree of foods and nutrients did not shape the microbial between-sample diversity. Additionally, high MDI was related with a high intake of pizza/hamburger, poultry, and light-vegetable combination. Conclusion: Our study contributed to current evidence of the microbiome structure and dysbiosis at different stages of CRC. Furthermore, history of smoking, alcohol consumption, and diabetes showed AKP effect in CRC patients. Non-significant association between dietary choices and microbiome diversity supported a small variation of microbiome profiles explained by dietary intake at the population level. Citation Format: Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Jeeyoo Lee, Aesun Shin. Modifiable factors and gut microbiome alteration among colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3062.

Background: The COVID-19 pandemic has disrupted healthcare delivery, which is widely discussed as the distraction effect. This study aimed to estimate the distraction effect of the COVID-19 pandemic in Korea by analyzing colorectal and gastric cancer screening rates in the years 2019 and 2020. Methods: Information of eligible population who had colorectal and gastric cancer screening provided by the National Cancer Screening Program in the years 2019 and 2020 was collected. Participation rates were analyzed by age group, sex, geographic region, and calendar month. Percentage change was calculated by dividing the percentage point difference by the screening rate of the reference period (2019). Results: Overall, the colorectal and gastric cancer screening rates had decreased in 2020, compared to the reference period. For colorectal cancer, the screening rate decreased from 68.3% in 2019 (5,886,319 participants/14,526,424 eligible population) to 54.6% in 2020 (5,135,218/9,410,525) For gastric cancer, the screening rates decreased from 61.9% in 2019 (7,194,489/11,625,627) to 54.6% in 2020 (6,244,491/11,439,246). In March, during the first wave, the screening rates declined sharply (percentage change: colorectal, 56.6%; gastric, 57.3%). Although the screening rates had rebounded aftermath, they declined again in December, during the third wave (percentage change: colorectal, 17.0%; gastric, 13.8%). According to specific-age group, we found a substantial decline in screening rates for older adults aged 80~84, and those over 85 (percentage change: colorectal, 19.0% & 23.0%; gastric, 17.4% & 25.1% respectively). Conclusion: During the COVID-19 pandemic, the screening rates for both colorectal and gastric cancer decreased. There was a substantial decline during the first and the third waves of the epidemic, in March and in December. The older adults group showed the highest reduction in screening rates. However, comparing the screening rate by region and sex, we did not find a significant difference. Delayed cancer diagnosis or excess death due to distraction effect of the COVID-19 pandemic has not yet been detected in Korea, therefore, further studies are needed. Citation Format: Seung Hee Seo, Hyeree Park, Jong Heon Park, Bhumsuk Keam, Shin Hye Yoo, Aesun Shin. Colorectal and gastric cancer screening rates in Korea during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 433.

Colorectal cancer is one of the common cancers worldwide. Obesity and physical activity are well-established risk factors for colorectal cancer. Studies have shown that as a consequence of energy metabolism, imbalance between energy intake and physical activity can lead to obesity. In order to precisely examine the close interrelationship between obesity, energy intake, and physical activity, we conducted a genome-wide interaction study of obesity with energy intake and physical activity. We also evaluated the interaction between obesity susceptibility loci with energy intake and physical activity for colorectal cancer using the nested case-control design. We analyzed data on participants in the UK Biobank. Genome-wide interaction analyses of obesity with energy intake and physical activity was performed on 65,514 and 250,369 participants who have information on genotype, body mass index, and energy intake/physical activity, respectively. We assessed the effect of obesity loci in the participants comprised 3523 colorectal cancer cases and 10,522 matched controls. The logistic regression model was used for finding obesity loci under a p-value threshold of 10-4. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer were estimated using a conditional logistic regression model. We found 21 loci and 44 loci of obesity with energy intake and physical activity, respectively. We also observed significant interaction of obesity loci with energy intake and physical activity for colorectal cancer. The obesity loci interacting with energy intake, including rs10828896 and rs7099260, were significantly interacted with physical activity for colorectal cancer. Rs426345 and rs12551684, which were the obesity loci interacting with physical activity, were significantly interacted with energy intake for colorectal cancer. The results of this study may provide evidence for bioenergetics in colorectal cancer carcinogenesis. Citation Format: Sooyoung Cho, Aesun Shin. Interaction of obesity loci with energy intake and physical activity on the risk of colorectal cancer: Evidence from UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1454.

Background: Twenty percent of soy production is consumed directly by humans worldwide. However, epidemiological findings on the association between soybean products consumption and gastric cancer risk remain inconsistent. We evaluated the relationship between soybean products consumption and the risk of gastric cancer in a prospective cohort study in Korea. Methods: This prospective cohort study included a total of 139,267 participants (men 46,953 and women 92,314) aged 40-69 years from the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis was retrieved from the Korea Central Cancer Registry until 31 December 2018. Multivariate hazard ratios (HRs) and 95% of confidence intervals (CIs) for the risk of gastric cancer according to the consumption of soybean products were estimated using Cox proportional hazards models with age as the time scale. Results: A total of 884 incident cases of gastric cancer (men 480 and women 404) occurred over an average follow-up period of 9.20 years (men 9.18 years and women 9.21 years). We found that soybean products consumption is associated with the lower risk of gastric cancer among Koreans (the multivariate HRs for tofu consumption of more than two servings/week were 0.93 (95% CI: 0.68, 1.26; NS) among women and 0.63 (95% CI: 0.45, 0.89) among men). Among men with a body mass index of less than 25kg/m2, increased consumption of soybean paste (p for trend = 0.0188) and tofu (more than two servings/week vs. almost never consumed; HR 0.51 (0.32, 0.82) p for trend = 0.0095) was associated with decreased risk for gastric cancer. Conclusion : Our results suggest that a high consumption of soybean products has a protective effect against gastric cancer Citation Format: Woo-Kyoung Shin, Hwi-Won Lee, Dan Huang, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-koo Lee, Jung Eun Lee, Daehee Kang. Soybean products consumption decreases risk for gastric cancer: Results from the Health Examinees study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5911.

Background: Several studies have examined associations between breast cancer risk and individual foods and nutrients. Most studies have evaluated risks associated with individual foods and nutrients, rather than measures of whole-diet. The objective of this study was to investigate the association between dietary patterns and the risk for breast cancer. Methods: A total of 93,306 women aged 40-69 years were enrolled in the prospective cohort study in the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis in the eligible cohort was retrieved from the Korea Central Cancer Registry through 31 December 2014. Dietary patterns were identified using factor analysis of data from a 106-item validated food frequency questionnaire. We conducted a multivariable Cox regression model to obtain the hazard ratio (HR) and 95% confidence interval (CI) for the risk of breast cancer according to the dietary pattern scores. Results: A total of 359 incident cases of breast cancer occurred over an average follow-up period of 6.3 years. Using a factor analysis, we identified three major dietary patterns, which explained 23.9% of the total variance, based on the daily total food intake (g/day) from 37 food groups: the Vegetables and seaweed pattern (greater intake of yellow-green and other vegetables, seaweed, lean fish, and shellfish), the Flour and meat pattern (greater intake of bread, pizza and hamburger, red meat, and poultry), the White rice and salt fermented fish pattern (greater intake of white rice and salt fermented fish). We found that the women who had higher white rice and salt fermented fish pattern scores tend to have higher risk of breast cancer. Multivariate HR (95% CI) comparing the highest with the lowest quintiles of White rice and salt fermented fish pattern scores was 1.35 (1.00, 1.84) (p for trend = 0.0384). Other two dietary patterns, the Vegetables and seaweed pattern and the Flour and meat pattern, showed no significant association with the breast cancer risk for women. Conclusion: The White rice and salt fermented fish pattern was associated with a increased risk of breast cancer, but further investigation involving subgroup analysis is warranted. Citation Format: Woo-Kyoung Shin, Hwi-Won Lee, Aesun Shin, Jong-koo Lee, Daehee Kang. Multi-grain rice diet decreases risk of breast cancer in Korean women: Results from the Health Examinees study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-279.

Background: The global trend of obesity, or the “obesity epidemic,” is not confined to adults. The increasing rates of obesity at young age signifies potential burden to our society as a whole, and requires prompt attention. Although emerging evidence has indicated a possible link of obesity in early life to subsequent cancer risks, the association with gastric cancer remains largely unknown, especially among the populations with high incidence rates of gastric cancer. Objective: Using data from the Health Examinees (HEXA) study of Korea, this study aimed to investigate the association of obesity at younger age (ages 18-20 and 35) with the later risk of gastric cancer in a population with high incidence rate of gastric cancer. Method: Included were 114,155 cancer-free subjects who participated in the large-scale prospective cohort study of the Health Examinees-Gem (HEXA-G) study during 2004-2013. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for gastric cancer risk associated with body mass index (BMI) at age 18-20 and 35. To consider substantial differences in incidence rates between men and women, the overall associations were further evaluated, separately by sex. Results: During a median follow-up period of 6.2 years, 851 gastric cancer cases (476 men and 375 women) were identified. When compared to normal BMI (18.5 - 23.0kg/m2), obesity (BMI ≥30kg/m2) at age 35 was significantly associated with increased risk of gastric cancer later in life: HR (95% CI) = 2.60 (1.57-4.33) for total participants, 2.11 (1.03-4.34) for men, and 3.82 (1.86-7.86) for women. No significant associations were found for obesity at late adolescence in both men and women. Conclusion: Our findings suggest that obesity in early adulthood may be associated with increased risk of gastric cancer. Preventing obesity in early life may help reduce the health burden of gastric cancer in later life. Citation Format: Hwi-Won Lee, Woo-Kyoung Shin, Jae Jeong Yang, Minkyo Song, Aesun Shin, Jong-koo Lee, Daehee Kang. Obesity at early adulthood increases subsequent risk of gastric cancer in high incidence nation: Results from the Health Examinees-Gem (HEXA-G) study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-157.

Background: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. Methods: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). Results: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P = 0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P = 0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. Conclusions: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. Impact: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk. Cancer Epidemiol Biomarkers Prev; 19(5); 1292–300. ©2010 AACR.

Transforming growth factor-β (TGF-β) inhibits the proliferation of carcinomas in early stages of breast cancer, whereas it promotes tumor growth and metastasis in later stages of cancer. We evaluated a possible association between TGF-β1 gene polymorphisms and breast cancer risk in a population-based case-control study of Chinese women living in Shanghai, which included 1,127 breast cancer cases and 1,228 population controls. Two polymorphisms, C-509T and T+29C, were in strong linkage disequilibrium. There were no overall differences in the genotype distribution of T+29C polymorphisms of the TGF-β1 gene among cases and controls. However, the distribution of the high-activity C allele of T+29C polymorphisms differed by cancer stages (Ptrend = 0.02). This allele was associated with decreased risk of early-stage breast cancer [stages 0 and I; odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54-0.99], and the OR was further reduced to 0.66 (95% CI, 0.45-0.96) for those homozygous for this allele (Ptrend = 0.03). On the other hand, the same allele was associated with nonsignificantly increased risk of breast cancer with advanced stages III and IV (OR, 1.33; 95% CI, 0.81-2.18), which differed significantly from that observed for early-stage cancer (P = 0.04). This result suggests a possible dual effect of TGF-β1 shown by in vitro experiments and provides an explanation for some of the inconsistent findings from previous epidemiologic studies that did not evaluate this association by cancer stage.

Gastric cardia and non-cardia cancer differs in their descriptive patterns and risk factors. The objective of this study was to determine the global trends in incidence of cardiac and non-cardiac gastric cancer. Ninety two high quality registries with the proportion of Not Otherwise Specified (NOS) gastric cancer (ICD-10 code C16.8-9) below 50% and the total number of gastric cancer cases above 300 were selected from 225 registries in Cancer Incidence of Five Continent (CI5) volume 9 and 262 registries from CI5 volume 10. The NOS cases were re-distributed to cardia and non-cardia according to the registry-specific proportion. Age-standardized incidence rates (ASRs) per 100,000 population and incidence rate ratios (IRR) from 1998-2002 to 2003-2007 were calculated. Non-cardia cancer incidence was significantly decreased in 5 out of 10 Asian registries, 17 out of 18 European registries, 27 out of 56 North American registries, and all 5 Oceanian registries in men. Only two registries in Asia showed a significant increase in non-cardia cancer incidence. In contrast, cardia cancer significantly increased in one Asian registry, two European registries, and two North American registries. Significant decrease in cardia cancer was observed in 3 Asian registries, 6 European registries, 11 North American registries, and 3 Oceanian registries in men. In women, six registries (1 Asian, 2 European, and 3 North American) showed significant increase in non-cardia cancer, whereas registries 25 (3 Asian, 13 European, 8 North American, and 1 Oceanian) showed significant decrease in non-cardia cancer incidence. Cardia cancer in women increased in 16 registries (2 Asian and 14 North American) and decreased in 9 registries (1 Asian, 5 European, and 3 North American). In conclusion, non-cardia cancer incidence decreased in most registries, whereas decrease in cardia cancer is more prominent in men but not in women. Citation Format: Aesun Shin, Dalis Seungeun Kim, Hyungtaek Woo. Global transition in cardia and non-cardia gastric cancer incidence, 1998-2007 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 265. doi:10.1158/1538-7445.AM2017-265

Backgrounds: Attenuation by genistein, an isoflavone abundant in soybean, of gastric carcinogenesis induced by sodium chloride was reported in an animal study. Up to date, role of isoflavone as an effect modifier on the association between salt intake and gastric cancer risk is not clearly established. Methods: We randomly selected 640 subcohort subjects without cancer history at enrollment from the Korean multi-center cancer cohort participants. Ninety-nine gastric cancer cases were identified from the inside (N=8) and the outside (N=91) of the subcohort after the 12.2 years of median follow-up time. To estimate individual’s salt intake, we measured 24-hour urinary sodium excretion from spot urine using the Tanaka’s equation. Three isoflavone plasma concentrations (Genistein, daidzein, and equol) of 167 subjects among case-cohort subjects had been measured using time-resolved fluoroimmunoassay. Cubic spline curve for gastric cancer risk according to urinary sodium level was used to define optimal cut-off points of urinary sodium excretion concentration. Weighted Cox proportional hazard regression was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs). Stratified analysis by isoflavone level was conducted to assess effect modification by isoflavone on the association between salt intake and gastric cancer. Results: Gastric cancer risk in the high salt intake group (urinary sodium excretion ≥6,000mg/day) was significantly increased (HR, 1.69; 95% CI, 0.99-2.90) compared to the reference group (urinary sodium excretion 4500-5,999mg/day). Magnitudes of gastric cancer risk by high salt intake were more strengthened in the group with low plasma isoflavone concentrations (One or no genistein, diadzein or equol levels over the median concentrations) (HR, 6.92; 95% CI, 1.80-26.56). Contrary to the low isoflavone group, no significant differences in gastric cancer risk according to salt intake levels were found in the group with high isoflavone concentration. Conclusions: High salt intake is associated with gastric cancer risk, but this association can be attenuated by high concentration of isoflavones. We suggest that sufficient intake of soybean products, the rich sources of isoflavone, may give protection against gastric cancer in the population with high salt intake. Citation Format: Jieun Jang, Yunji Hwang, Choonghyun Ahn, Kwang-Pil Ko, Aesun Shin, Keun-Young Yoo, Sue K. Park. Effect modification by isoflavones on the association between salt intake and gastric cancer risk: A case-cohort study within the Korean multi-center cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2017-2276

Introduction Nuts consumption has been associated with reduced risk of obesity, diabetes mellitus, and cardiovascular diseases. However, the association between nuts and colorectal cancer risk remains unclear. Objective In this study, we aimed to investigate the relationship between nuts consumption and colorectal cancer risk in a case-control study. Methods A case-control study was conducted with 923 colorectal cancer patients and 1846 controls recruited from the National Cancer Center in Korea. Information on dietary intake was collected using a food frequency questionnaire (FFQ) with 106 items. Nuts consumption level was classified by sex-specific quartile of control group. Binary and polytomous logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) for the association between nuts consumption and colorectal cancer risk. Results High nuts consumption was strongly associated with a reduced risk of colorectal cancer in women (OR, 0.18; 95% CI 0.10-0.32 for highest vs. lowest quartile) and similar inverse association was observed for men (OR, 0.36; 95% CI 0.25-0.52). In subsite analysis, adjusted ORs (95% (CI)) comparing the highest vs the lowest quartile of nuts consumption were: 0.49 (0.24-0.99) for proximal colon cancer, 0.38 (0.23-0.64) for distal colon cancer, and 0.29 (0.18-0.46) for rectal cancer in men. An inverse association was also found in women for proximal colon cancer (0.16 (0.05-0.51)), distal colon cancer (0.16 (0.07-0.37)) and rectal cancer (0.25 (0.12-0.51)). Conclusion We found a statistically significant association between higher nuts intake and reduced risk of colorectal cancer and the association was observed for all subsites of colorectum in both men and women. Citation Format: Jeeyoo Lee, Aesun Shin, Jeonghee Lee, Ji Won Park, Jae Hwan Oh, Jeongseon Kim. The relationship between nut consumption and risk of colorectal cancer. [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 1748.

Objectives: To examine the association between body mass index (BMI), physical activity and colorectal cancer risk among Korean adults. Methods: Data from the Korean Multi-center Cancer Cohort (KMCC) between 1993 and 2005 were analyzed. The study population comprised 12,379 subjects aged above 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 10.1 years). Measured weight and height values was used to calculate BMI and self-reported total time spent for physical activity were used. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of BMI and physical activity for colorectal cancer risk. Results: Men who did moderate physical activity showed a lower risk for colorectal cancer (HR 0.35, 95% CI: 0.19-0.65 for 30-419 minutes compared to who spend less than 30 minutes a week doing moderate activities). We did not find any association between the total time of vigorous activities and muscle-strengthening activities and colorectal cancer risk in both men and women. Men with BMI of 25 or higher showed an increased risk for colorectal cancer compared to men with BMI of 18.5 to 22.9 (HR 1.64, 95% CI 0.94-2.88 for 25.0-29.9 kg/m2; HR 1.64, 95% CI 0.94-2.88 for greater than 30.0 kg/m2). Conclusions: Moderate physical activities were associated with lower colorectal cancer risk among Korean men. Citation Format: Sooyoung Cho, Aesun Shin, Sue K. Park, Hai-Rim Shin, Soung-Hoon Chang, Keun-Young Yoo. Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC). [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 1734.

BACKGROUND: This study aimed at investigating the individual and area level factors associated with colorectal cancer screening attendance. METHODS: Colorectal cancer screening participation as well as other individual level data were gathered from the fifth Korea National Health and Nutrition Examination Survey, 2010-2012. The area level data were extracted from 2009 Health promotion strategies and programs development for health inequalities alleviation (Shin et al.,2009). Multilevel model was used for data analysis. RESULTS: Information on a total of 8,783 individuals (3,777 men and 5,006 women) aged 50 years and older and deprivation index of each areas were used in the final analysis. Among individual level variables, men were more likely to participated in colorectal cancer screening within 5 years than women (58.0% for men vs 53.9% for women)(Odds Ratio (OR) = 0.85; 95% CI 0.73 to 0.99), and highest among age 60-69 (63.3%). Area level variables's explained class-level variance was 6.4%. CONCLUSION: In this study, by applying the multilevel analysis we can find that colorectal cancer screening attendance rate is associated with both individual and community factors. Citation Format: Aesun Shin, Hyeongtaek Woo. Determinants for compliance to colorectal cancer screening in Korea: A multilevel analysis. [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 2581.

Background & Objective: The incidence of thyroid cancer has been increased in several countries. However, the markers to predict for high-risk group have not been fully established. We aim to investigate the potential association between the biomarkers of thyroid function/autoimmunity and the risk of thyroid cancer in Korean population, where the incidence rate of thyroid cancer is one of the highest in the world. Design: This study was a nested case-control study within the Cancer Screenee Cohort study, which consisted of 257 incident thyroid cancer patients who were ascertained during mean of 2.2 years of follow-up and 257 controls. Total triidothyronine (TT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroglobulin (Tg), and two markers of thyroid autoimmunity (anti-thyroperoxidase [TPOAb] and anti-thyroglobulin [TgAb] antibodies) were measured. Logistic regression models were used to examine the association between these biomarkers and thyroid cancer risk. Stratified analyses were conducted by sex, BMI, and smoking status. Results: When the markers were categories by tertile distribution of the levels of controls group, highest tertile of FT4 (OR [95% CI] = 1.73[1.11, 2.69]) and middle tertile of TSH (OR [95% CI] = 1.77[1.14, 2.74]) were associated with thyroid cancer risk in multivariate analyses. In addition, normal (30-60 U/mL) (OR [95% CI] = 8.47 [5.39, 13.33]) or elevated levels (60 > U/mL) (OR [95% CI] = 4.48 [2.59, 7.76]) of TPOAb showed an elevated risk for thyroid cancer. Stratified analyses implied that some of these associations could be differed by sex, BMI, or smoking status. Conclusions: This study represented that the levels of biomarkers of thyroid function/autoimmunity, particularly the presence of TPOAb, may be used as diagnostic adjuncts for predicting thyroid cancer risk. Citation Format: Jeongseon Kim, Young Ae Cho, Aesun Shin, Jeonghee Lee, Sun-Young Kong, Eun Kyung Lee, You Jin Lee. Biomarkers of thyroid function and autoimmunity associated with thyroid cancer risk: A nested case-control 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 4103. doi:10.1158/1538-7445.AM2014-4103

Background The association of soybean products related with colorectal cancer risk is inconsistent. This may be due to information bias from measuring food intake by questionnaires and different degrees of bias according to study design. To assess the association between soybean products and colorectal cancer, we directly measured phytoestrogen biomarkers in a nested case-control study in Korea. Methods Study population was composed of 101 cases and 398 matched controls matched for age within 5-year, sex, area and year at recruitment of cases within the Korean Multicenter Cancer Cohort. The concentrations of four biomarkers in the plasma were measured by Liquid Chromatography-Mass Spectrometry. Conditional logistic regression models were used to calculate the odds ratio and 95% confidence intervals (CI). Results Median plasma concentrations of genistein, daidzein, glycitein and enterolactone were not statistically significant between cases and controls. However, there was a significant trend of decreasing risk according to an increase of genistein (p=0.03). This protective effect of genistein was more prominent in women. There was no association between other plasma concentrations of isoflavones or lignans and colorectal cancer. Conclusions High serum concentrations of isoflavones, i.e, genistein, were associated with a decreased trend of colorectal cancer, especially in women. Citation Format: Yohwan Yeo, Kwang-Pil Ko, Seung-Hyun Ma, Jae Jeong Yang, Aesun Shin, Sue K. Park, Soung-Hoon Chang, Hai-Rim Shin, Daehee Kang, Keun-Young Yoo. Isoflavones from phytoestrogens and colorectal cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort. [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 4823. doi:10.1158/1538-7445.AM2013-4823

Background: Genetic variations of interleukin-10 (IL-10) and environmental factors are assumed to influence inflammation and gastric carcinogenesis. Therefore, we aimed to investigate the association between IL-10 polymorphisms, smoking, and Helicobacter pylori (H. pylori) infection on the noncardia gastric carcinogenesis in Koreans. Methods: We genotyped 3 promoter polymorphisms (−1082 A>G, -819T>C, -592A>C) on the IL-10 gene in 495 noncardia gastric cancer patients and 495 sex- and age-matched controls. Multiple logistic regression models were used to detect the effects of IL-10 genetic variants, smoking, and H. pylori infection on gastric cancer risk, stratified by histological type of gastric cancer. Results: The IL-10-819C allele and -592C allele are in complete linkage disequilibrium, and IL-10-819C/-592C carriers are associated with a higher risk of noncardia gastric cancer, particularly with a risk of intestinal type cancer (OR [95% CI] = 1.50 [1.08−2.08]), than those with the wild type homozygote genotypes. Compared to nonsmokers carrying the wild type homozygotes, current smokers carrying IL-10-1082G and -819C/-592C showed 4.91 (95% CI = 2.49−9.69) and 6.82 (95% CI = 2.94−15.84) times increased risk of intestinal type gastric cancer, respectively. In addition, smokers with H. pylori infection were in the highest risk of intestinal gastric cancer compared with non-smokers without H. pylori infection, and this association was particularly stronger among IL-10-1082G carriers than AA carriers (OR [95% CI] = 15.54 [5.52−43.72]). Conclusion: Inflammation-related genetic variants may interact with smoking and H. pylori infection on the risk of noncardia gastric cancer, particularly intestinal type. Therefore, high risk group may reduce the risk of gastric cancer by modifying their lifestyles. 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 3745. doi:10.1158/1538-7445.AM2011-3745

Objective: We investigated the role of single nucleotide polymorphisms (SNP) ODC-polyamine pathway related genes (ODC1, AMD1, OAZ2, NQO1, NOS2A) for gastric cancer risk. Additionally, we examined whether phytoestrogen levels modify the association of ODC-polyamine pathway SNPs and risk of gastric cancer. Materials and Methods: Twenty-five SNPs in five genes were genotyped in 59 incident gastric cancer cases and 175 matched controls recruited from the Korea Multi-Center Cancer Cohort. Candidate genes were selected based on genotype databases, and genotype assay was performed using Goldengate platform (Illumina). We calculated the unadjusted Wald p-value between each SNP and phytoestrogen level, as well as the false discovery rate (FDR) corrected p-values of the 25 SNPs according to each phytoestrogen biomarker. Unconditional logistic regression model was used to calculate the adjusted odds ratios (OR) and 95% CI for smoking history. Results: There was a significant association for NQO1 (rs1800566, rs1437135) and daidzein, AMD1 (rs1279599, rs7768897, rs811921) and equol, AMD1 (rs1279599, rs7768897, rs811921) and enterolactone (FDR p-value Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 936.

Objectives: Cytotoxin-associated antigen (CagA) produced by Helicobacter pylori (H. pylori) plays a role in gastric carcinogenesis, but the role of genes coding proteins in the CagA pathway remains unclear. This genetic association study aimed to evaluate which genes involved in CagA signal transduction pathway are associated with gastric cancer development. Methods: By literature reviews, we selected 34 candidate genes involved in CagA signal transduction pathway and screened a total of 580 SNPs within +/- 5kbp of target gene location. Within the Korean Multi-Center Cancer Cohort (KMCC), a 100 incident gastric cancer cases were matched to a cancer-free subject by age, sex, residential area and enrollment. Both raw and permutated p-values by 10,000 permutation tests were computed using the LRT with 1 degree of freedom in the trend model. Gastric cancer risk was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, smoking status, H. pylori infection, and CagA IgG antibody positivity in each genetic model. Results: Twenty five SNPs in 8 genes, Erk, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk, were significantly associated with gastric cancer risk in the single SNP analysis (p Conclusions: Our findings indicate that genes involved in the CagA signal transduction pathway can be major susceptible factors related to tyrosine kinase action, especially interaction with Crk. Further replication studies with wider genomic coverage and a greater number of subjects are still needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2845.

Colorectal cancer incidence and mortality have been gradually increasing during the last few decades in Korea. Growing evidences revealed etiological differences among proximal colon, distal colon, and rectal cancer. Furthermore, the proportion of rectal cancer among colorectal cancer incidence in Korean people is over 40%. This is relatively high compared to that observed among Western population. We investigated the association between colorectal cancer risk factors and different sites of colorectal cancers based on a large Health Insurance Study. Included in this study were 869,725 men and 395,501 women who were beneficiaries or dependent family members of the insured who were cancer-free at baseline between 1996 and 1997, participating in the National Health Insurance Corporation Study (NHICS) were followed for up to 7 years. The Cox proportional hazard model was used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) with adjustment for age. During up to 7 years of follow-up, 4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women). Height was associated with an elevated risk for left colon cancer and rectal cancer in men (HR=1.02, 95% CI=1.01-1.03 for left colon cancer and HR=1.01, 95% CI=1.00-1.02 for rectal cancer, per 1 cm increments) and that for rectal cancer in women (HR=1.03, 95% CI=1.01-1.04, per 1 cm increments). Family history of cancer was associated with a higher risk for cancer of right colon (HR=1.40, 95% CI=1.14-1.72) and left colon (HR=1.31, 95% CI=1.12-1.55) in men, and for cancer of left colon (HR=1.57, 95% CI=1.20-2.06) in women. Frequent alcohol consumption and high consumption amount were associated with an elevated risk for left colon cancer in men. Men who consumed alcoholic beverages 3-4 times per week showed 1.65-fold increase risk for left colon cancer compared to non-drinkers (95% CI=1.32-2.06, p-trend Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-396.

It is widely known that vegetable consumption contributes to reducing the risk of gastric cancer (GC). However, the incidence rates of GC remain high in both Japanese and Korean populations, although they have a high consumption of total vegetables. It may be due to the fact that Japanese and Koreans mainly consume processed vegetables, such as cooked, salted, or pickled vegetables, rather than fresh vegetables. To determine whether the intakes of fresh and pickled vegetables have different effects on the risk of GC in Japanese and Korean populations, we conducted a meta-analysis of the epidemiological literature. Eight studies on the consumption of fresh vegetables and 14 studies on the consumption of pickled vegetables related to GC risk were included in this meta-analysis. Four studies exploring differences in GC risk in men and women were considered separately. We observed that a high intake of fresh vegetables was significantly associated with a decreased risk of GC (overall summary OR=0.62, 95% CI=0.46–0.85) but that a high intake of pickled vegetables was significantly associated with an increased risk of GC (overall summary OR=1.28, 95% CI=1.06–1.53). The results of this meta-analysis provide evidence that a high intake of pickled vegetables may increase GC risk and suggest that a high consumption of fresh vegetables, rather than a large total amount of vegetables including pickled vegetables, is important to reduce GC risk. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B104.