Korean Multi-center Cancer Cohort Research Articles

Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults.

The potential differences by sex in the association between body mass index (BMI) and thyroid cancer risk remain unconfirmed. Data from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS; 2002-2015; population size = 510,619) and the Korean Multi-center Cancer Cohort (KMCC) data (1993-2015; population size = 19,026) were used. We constructed Cox regression models, adjusted for potential confounders, to evaluate the association between BMI and thyroid cancer incidence in each cohort, and assessed the consistency of the results. In the NHIS-HEALS, 1,351 and 4,609 incident thyroid cancer cases occurred during the follow-up among men and women, respectively. Compared with BMI of 18.5-22.9 kg/m2, BMI of 23.0-24.9 [no. of cases = 410; HR, 1.25; 95% confidence interval (CI), 1.08-1.44], 25.0-29.9 (no. of cases = 522; HR, 1.32; 95% CI, 1.15-1.51), and ≥30.0 kg/m2 (no. of cases = 48; HR, 1.93; 95% CI, 1.42-2.61) were associated with an increased risk of incident thyroid cancer among males. Among females, BMI of 23.0-24.9 (no. of cases = 1,300; HR, 1.17; 95% CI, 1.09-1.26) and 25.0-29.9 (no. of cases = 1,406; HR, 1.20; 95% CI, 1.11-1.29) were associated with incident thyroid cancer. The analyses using the KMCC demonstrated results consistent with wider CIs. Sex differences in the associations between BMI and thyroid cancer incidence were observed in Korean cohorts. BMI <23 kg/m2 may help prevent incident thyroid cancer, especially among men.

The Association between Plasma Concentration of Phytoestrogens and Hypertension within the Korean Multicenter Cancer Cohort.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case–control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20–0.57; enterolactone, OR = 0.32, 95%CI 0.18–0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26–0.96; OR = 0.38, 95%CI 0.19–0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22–0.81; OR = 0.28, 95%CI 0.14–0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history.

Fasting plasma glucose level was linearly associated with colorectal cancer (CRC) risk. However, the dose–response relationship between fasting blood glucose (FBG) and CRC risk was still uncertain.A total of 11,632 patients without self-reported diabetes mellitus and colorectal polyps’ history were identified in the Korean Multicenter Cancer Cohort (1993–2005). The nonlinear relationship was estimated through a restricted cubic spline regression, and a two-piece-wise Cox proportional hazards model was further performed to calculate the threshold effect. Multiple imputation was used to control the bias from missing data.Overall, 1.1% (n = 132) of participants were diagnosed with CRC in the follow-up duration. With a median follow-up duration of 12.0 years, participants with FBG ≥126 mg/dL were associated with higher CRC risk (adjusted hazard ratio [HR], 1.67; 95% confidence interval [CI]: 1.01, 2.76). Landmark analyses limited to long-term survivors demonstrated increased CRC risk with FBG ≥ 126 mg/dL in all subsets (≥3years: HR,1.93 (95% CI: 1.13–3.29); ≥5years: HR, 2.04 (95% CI: 1.–3.63); ≥10years: HR, 2.50 (95% CI: 1.19–5.25)). With FBG smoothly increasing before, the latter increased dramatically after the turning point (P for nonlinearity = 0.283). When FBG was increasing per mmol/L, HR was 1.07(95% CI: 0.90, 1.29) for FBG < 126 mg/dL and 1.27 (95% CI: 1.06, 1.53) for FBG ≥ 126 mg/dL. Besides, HR was 1.09 (95% CI: 1.02, 1.16) for the CRC risk.In the population without self-reported diabetes mellitus and colorectal polyps’ history. FBG was linearly associated with CRC risk, especially for FBG over 126 mg/dL.

Pickled Vegetable and Salted Fish Intake and the Risk of Gastric Cancer: Two Prospective Cohort Studies and a Meta-Analysis.

An increased risk of gastric cancer for pickled vegetable and salted fish intake has been suggested, yet the lack of a dose-response association warrants a quantitative analysis. We conducted a meta-analysis, combining results from our analysis of two large Korean cohort studies and those from previous prospective cohort studies. We investigated the association of pickled vegetable and salted fish intake with gastric cancer in the Korean Genome Epidemiology Study and the Korean Multi-center Cancer Cohort Study using Cox proportional hazard models. We then searched for observational studies published until November 2019 and conducted both dose-response and categorical meta-analyses. The pooled relative risk (RR) of gastric cancer incidence was 1.15 (95% Confidence Interval (CI), 1.07–1.23) for 40 g/day increment in pickled vegetable intake in a dose-response manner (P for nonlinearity = 0.11). As for salted fish intake, the pooled risk of gastric cancer incidence was 1.17 (95% CI, 0.99–1.38) times higher, comparing the highest to the lowest intake. Our findings supported the evidence that high intake of pickled vegetable and salted fish is associated with elevated risk of gastric cancer incidence.

86P - The impact of newly diagnosed diabetes mellitus on cancer-free survival in patients without colorectal polyps: A secondary analysis of Korean multicenter cancer cohort

BackgroundObservational studies show that diabetes mellitus (DM) is associated with a higher risk of colorectal cancer (CRC). However, whether the relationship between DM and CRC will be influenced by the baseline characteristics of patients is still unclear. MethodsA total of 11632 patients without colorectal polyps and DM history were identified in the Korean Multicenter Cancer Cohort (1993-2005) and categorized in the diabetic group (DM; fasting glucose≥126mg/dL) versus normal group (non-DM; all other patients). Cancer-free survival was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models. The two groups (DM vs non-DM) were matched using propensity scores(PS) to control selection bias. To evaluate DM impact on CRC risk in relation to baseline characteristics, first multivariable Cox regression analysis was used to predict CRC risk in patients without DM, then interaction between predicted CRC risk and DM status was performed. ResultsOverall, 6.9% (n = 802) of patients were newly diagnosed diabetes mellitus. At a median follow-up of 12.0 years, patients with DM were associated with lower cancer-free survival(unadjusted HR, 1.83; 95%CI: 1.11 to 3.01). Landmark analyses limited to long-term survivors demonstrated improved cancer-free survival with DM in all subsets (≥3yr: unadjusted HR,1.93(95%CI:1.13 to 3.29); ≥5yr: HR, 2.04(CI:1.15 to 3.63); ≥10yr: HR, 2.50(CI: 1.19 to 5.25)). In the PS-matching cohorts, however, 10-yr cancer-free survival was not markedly higher in the non-DM group versus the DM group (99.0% vs 98.8%; p = 0.57). In multivariable Cox regression, the non-DM group, age, sex, BMI, alcohol consumption history and cigarette smoking history were predictors of CRC risk. This model was used to predict the 10-yr CRC risk. The interaction between predicted CRC risk and DM status was not significant. Specifically, the impact of DM on cancer-free survival was slight as predicted CRC risk less than 5%. ConclusionsIn this large prospective study, newly diagnosed diabetes mellitus was associated with a higher risk for colorectal cancer. This impact largely affected by baseline characteristics. Legal entity responsible for the studyXiong Chen. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

Abstract 636: Salted food intake and risk of gastric cancer: A pooled analysis of Korean cohorts and a global meta-analysis

Abstract Backgrounds: Gastric cancer, the fifth most common cancer, is the third most common cause of death from cancer with more than half of the cases occurring in Eastern Asia. The World Cancer Research Fund proposed “foods preserved by salting” as probable risk factors of gastric cancer, as evidenced from epidemiological studies addressing high salt foods and gastric cancer. Methods: We conducted a pooled analysis of Korean cohorts, The Korean Genome Epidemiology Study (KoGES) and Korean Multi-center Cancer Cohort Study (KMCC) to investigate the association between salted food intake and gastric cancer mortality among Korean population. We used cox proportional hazard models adjusted for potential confounding factors. We also reviewed global observational studies published until October 2018 and conducted a dose-response and a categorical meta-analysis. We used either a random effect model or a fixed effect model depending on the heterogeneity of the studies. We further categorized salted food into salted vegetable, fish, and soup to examine the relative risk (RR) of gastric cancer for specific salted foods. Results: The pooled RRs (95% confidence intervals, CIs) of gastric cancer among KoGES and KMCC were 0.99 (0.95-1.04) per 50g increase in salted food intake and 0.98(0.94-1.03), 1.79(1.05-3.06), 1.17(0.95-1.43) per 50g increase in intake of salted vegetable, fish, and soup, respectively. The pooled RR (95% CI) of gastric cancer, compared with the lowest category of salted food intake, was 0.95(0.63-1.27) for the highest category of intake. For the dose-response meta-analysis, we included 35 studies (15 cohort and 20 case-control), and the combined global RRs (95% CIs) of gastric cancer per 50g increase in intake were 1.07 (1.02-1.12) for salted food and 1.11(1.03-1.20), 2.10(1.27-3.46), 1.00(0.99-1.01) for salted vegetable, fish, and soup, respectively. When we analyzed prospective studies only, the RRs (95% CIs) per 50g increase in intake were 1.02(0.99-1.06) for salted food and 1.05(0.98-1.13), 1.26(1.01-1.59), 1.00(0.99-1.01) for salted vegetable, fish, and soup, respectively. For the categorical meta-analysis, 69 studies (23 cohort and 46 case-control) were included; the combined RRs (95% CIs) of the highest intake category, compared to the lowest intake category, were 1.19(1.11-1.27), 1.30(1.19-1.40), 1.06(0.95-1.16), and 1.03(0.92-1.14) for salted food, vegetable, fish, and soup, respectively. Conclusions: The pooled analysis showed a statistically significant association between risk of gastric cancer and salted fish intake among Korean population. The global meta-analyses also showed a significant association between intake of salted food and risk of gastric cancer. Acknowledgements: This study was funded by the Korean Foundation for Cancer Research (Grant Number. CB-2017-A-2) Citation Format: Jin Young Yoo, Hyun Jeong Cho, Sungji Moon, Inah Kim, Kwang-Pil Ko, Sue Kyung Park, Jung Eun Lee. Salted food intake and risk of gastric cancer: A pooled analysis of Korean cohorts and a global meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 636.

Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection.

PurposeFew studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information.Materials and MethodsWe performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model.ResultsIncreased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori.ConclusionThis study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

Fasting glucose and risk of colorectal cancer in the Korean Multi-center Cancer Cohort.

Previous cohort studies have demonstrated a positive association between diabetes mellitus (DM) and colorectal cancer (CRC). However, there are few comparisons between DM groups categorized by fasting glucose level. This study examined associations between diabetes as defined by fasting glucose level and self-reported history of DM and CRC risk among Korean adults. Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 14,570 participants aged 20 years or older. Participants were followed until December 31, 2012 (median follow-up: 11.9 years). Among participants with high fasting glucose (≥126mg/dL), the risk of developing CRC was significantly higher (HR: 1.51 [1.02–2.25]) than among participants with low fasting glucose (<126mg/dL). Risk was not significantly higher among participants with self-reported history of DM (HR: 1.34 [0.78–2.31]). When both fasting glucose and history of DM were considered together, the risk of CRC among participants with both high fasting glucose and history of DM was 54% (HR: 1.54 [0.97–2.43]), and the risk of CRC among participants with high fasting glucose and no history of DM was 50% (HR: 1.50 [0.73–3.05]). When the first 5 years of follow-up were excluded, among participants with high fasting glucose, the risk of developing CRC was significantly higher (HR: 1.61 [1.02–2.56]) than among participants with low fasting glucose. Risk of CRC was also significantly higher among participants with high fasting glucose and no history of DM (HR: 1.69 [1.01–2.84]). High fasting glucose and self-reported history of DM were associated with increased risk of CRC in this Korean population.

Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations

To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend=0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI)=0.46 (0.30-0.69), and COR (95% CI)=0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

Abstract 2276: 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 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

Effectiveness of Gastric Cancer Screening on Gastric Cancer Incidence and Mortality in a Community-Based Prospective Cohort.

PurposeThis study was performed to investigate the effectiveness of gastric cancer (GC) screening methods in a community-based prospective cohort of the Korean Multi-center Cancer Cohort (KMCC) with over a 10-year follow-up.Materials and MethodsA total 10,909 and 4,773 subjects from the KMCC with information on gastroendoscopy (GE) and upper gastrointestinal series (UGIS) were included in this study. Cox proportional hazard model adjusted for age, sex, Helicobacter pylori infection, cigarette smoking, and alcohol drinking was used to estimate the hazard ratios (HRs) and 95% confidence interval (CI).ResultsThe GE screened subjects had almost half the risk of GC-specific death than that of unscreened subjects (HR, 0.58; 95% CI, 0.36 to 0.94). Among the GC patients, GE screenees had a 2.24-fold higher survival rate than that of the non-screenees (95% CI, 1.61 to 3.11). In particular, GE screenees who underwent two or more screening episodes had a higher survival rate than that of the non-screenees (HR, 13.11; 95% CI, 7.38 to 23.30). The effectiveness of GE screening on reduced GC mortality and increased survival rate of GC patients was better in elderly subjects (≥ 65 years old) (HR, 0.47; 95% CI, 0.24 to 0.95 and HR, 8.84; 95% CI, 3.63 to 21.57, respectively) than that in younger subjects (< 65 years old) (HR, 0.66; 95% CI, 0.34 to 1.29 and HR, 1.83; 95% CI, 1.24 to 2.68, respectively). In contrast, UGIS screening had no significant relation to GC mortality and survival.ConclusionThe findings of this study suggest that a decreased GC-specific mortality and improved survival rate in GC patients can be achieved through GE screening.

Abstract 1734: Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC)

Abstract 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.

Abstract 4293: Combination of hepatocyte growth factor, genistein and daidzein concentrations as a biomarker for gastric cancer risk: A nested case-control study

Abstract Backgrounds: Hepatocyte growth factor (HGF) induces ERK pathway which is associated with carcinogenesis by promoting cell proliferation. Inhibition of ERK signal transduction pathways by genistein, one of the isoflavones, has been reported by several in vitro studies. Therefore, gastric cancer risk by HGF and isoflavone concentrations was evaluated in this study. Methods: Nested case-control study with 93 gastric cancer cases and 1:1 matched controls was conducted within the Korean Multi-center Cancer Cohort (KMCC). HGF and ISF (genistein, daidzein, equol) concentrations in plasma were measured with enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay, respectively. Odds ratios (ORs) and 95% confidence intervals (95% CIs) on gastric cancer risk according to HGF and ISF level was calculated using conditional logistic regression models. Results: Compared to the group with low level of HGF (&amp;lt;315pg/mL) and high level of genistein (≥212.5nmol/L), the group having high level of HGF and lower level of genistein was associated with increased gastric cancer risk (OR = 5.08, 95% CI = 1.39-18.57). Elevated gastric cancer risk in the subjects having high HGF level and low daidzein level than subjects with low HGF and high daidzein levels was also shown (OR = 3.67, 95% CI = 1.18-11.45). There was significant interaction between HGF and genistein levels on gastric cancer was found (p for interaction&amp;lt;0.01). Continual increase in gastric cancer risk according to the counts of risky status by HGF, genistein, and daidzein levels was found (p for trend = 0.03). Conclusion: Our study suggests that combination of HGF, genistein and daidzein concentrations has potential as a biomarker for gastric cancer risk. Citation Format: Jieun Jang, Yunji Hwang, Choonghyun Ahn, Kwang-Pil Ko, Keun-Young Yoo, Sue K. Park. Combination of hepatocyte growth factor, genistein and daidzein concentrations as a biomarker for gastric cancer risk: A nested case-control study. [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 4293.

Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status.

Background:Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk.Methods:We selected 949 case–cohort participants from the 18 863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs).Results:Relative to non-drinking, heavy drinking (⩾7 times a week), and binge drinking (⩾55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13–10.73) and 3.27-fold (95% CI, 1.01–10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori.Conclusions:Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori.

Alcohol Drinking, Cigarette Smoking and Risk of Colorectal Cancer in the Korean Multi-center Cancer Cohort.

Background:The present study aimed to examine the association between cigarette smoking, alcohol consumption and colorectal cancer risk among Korean adults.Methods:Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 18,707 subjects aged older than 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 11.2 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals of cigarette smoking and alcohol consumption for colorectal cancer risk.Results:In men, longer duration and higher average amount of alcohol consumption were associated with elevated risk of colorectal cancer (HR 1.93 [1.17–3.18] for ≥ 30 years of consumption compared to non-drinkers; HR 2.24 [1.31–3.84] for ≥ 30 g/d). Former smokers showed a non-significantly elevated risk of colorectal cancer in men. There was no apparent association between alcohol consumption or cigarette smoking and colorectal cancer risk among women.Conclusions:Alcohol consumption was associated with increased colorectal cancer risk among Korean men, and both a longer duration and a higher amount of consumption were associated with elevated risk.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95% confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR0.83 (95% CI0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR0.36 (95% CI0.15-0.90) and OR0.26 (95% CI0.10-0.64), respectively; p interaction<0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction<0.01). Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Korean Risk Assessment Model for Breast Cancer Risk Prediction

PurposeWe evaluated the performance of the Gail model for a Korean population and developed a Korean breast cancer risk assessment tool (KoBCRAT) based upon equations developed for the Gail model for predicting breast cancer risk.MethodsUsing 3,789 sets of cases and controls, risk factors for breast cancer among Koreans were identified. Individual probabilities were projected using Gail's equations and Korean hazard data. We compared the 5-year and lifetime risk produced using the modified Gail model which applied Korean incidence and mortality data and the parameter estimators from the original Gail model with those produced using the KoBCRAT. We validated the KoBCRAT based on the expected/observed breast cancer incidence and area under the curve (AUC) using two Korean cohorts: the Korean Multicenter Cancer Cohort (KMCC) and National Cancer Center (NCC) cohort.ResultsThe major risk factors under the age of 50 were family history, age at menarche, age at first full-term pregnancy, menopausal status, breastfeeding duration, oral contraceptive usage, and exercise, while those at and over the age of 50 were family history, age at menarche, age at menopause, pregnancy experience, body mass index, oral contraceptive usage, and exercise. The modified Gail model produced lower 5-year risk for the cases than for the controls (p = 0.017), while the KoBCRAT produced higher 5-year and lifetime risk for the cases than for the controls (p<0.001 and <0.001, respectively). The observed incidence of breast cancer in the two cohorts was similar to the expected incidence from the KoBCRAT (KMCC, p = 0.880; NCC, p = 0.878). The AUC using the KoBCRAT was 0.61 for the KMCC and 0.89 for the NCC cohort.ConclusionsOur findings suggest that the KoBCRAT is a better tool for predicting the risk of breast cancer in Korean women, especially urban women.

A Prospective Cohort Study on the Relationship of Sleep Duration With All-cause and Disease-specific Mortality in the Korean Multi-center Cancer Cohort Study

ObjectivesEmerging evidence indicates that sleep duration is associated with health outcomes. However, the relationship of sleep duration with long-term health is unclear. This study was designed to determine the relationship of sleep duration with mortality as a parameter for long-term health in a large prospective cohort study in Korea.MethodsThe study population included 13 164 participants aged over 20 years from the Korean Multi-center Cancer Cohort study. Information on sleep duration was obtained through a structured questionnaire interview. The hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using a Cox regression model. The non-linear relationship between sleep duration and mortality was examined non-parametrically using restricted cubic splines.ResultsThe HRs for all-cause mortality showed a U-shape, with the lowest point at sleep duration of 7 to 8 hours. There was an increased risk of death among persons with sleep duration of ≤5 hours (HR, 1.21; 95% CI, 1.03 to 1.41) and of ≥10 hours (HR, 1.36; 95% CI, 1.07 to 1.72). In stratified analysis, this relationship of HR was seen in women and in participants aged ≥60 years. Risk of cardiovascular disease-specific mortality was associated with a sleep duration of ≤5 hours (HR, 1.40; 95% CI, 1.02 to 1.93). Risk of death from respiratory disease was associated with sleep duration at both extremes (≤5 and ≥10 hours).ConclusionsSleep durations of 7 to 8 hours may be recommended to the public for a general healthy lifestyle in Korea.

Abstract 4823: Isoflavones from phytoestrogens and colorectal cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort.

Abstract 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

Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

BackgroundGastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC).MethodsThe KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs.ResultsFrequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268).ConclusionsFrequent soybean/tofu intake was associated with lower risk of gastric cancer.