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Purpose The association between tobacco smoking and thyroid cancer remains uncertain. We evaluated the associations of active and passive smokingwith the risk of papillary thyroid cancer (PTC), the most common type of thyroid cancer, and with the BRAFV600E mutation, the most common oncogenic mutation in PTC related to poor prognosis. Materials and methods We conducted this study with newly diagnosed PTC patients (n=2,142) and community controls (n=21,420) individually matched to cases for age and sex. Information on active and passive smoking and potential confounders were obtained from structured questionnaires, anthropometric measurements, and medical records. BRAFV600E mutation status was assessed in PTC patients. We evaluated the associations of active and passive smoking with PTC and BRAFV600E mutation risk using conditional and unconditional logistic regression models, respectively. Results We did not find associations between exposure indices of active and passive smoking and PTC risk in both men and women, except for the association between current smoking and lower PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAFV600E mutation risk in male PTC patients (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.30 to 1.00). The CI for the association was wider in female PTC patients (OR, 0.23; 95% CI, 0.02 to 2.62), possibly owing to a smaller sample size in this stratum. Conclusion We did not find consistent associations between active and passive smoking and PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAFV600E mutation risk in male PTC patients.

Purpose - Few 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 Methods - We 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. Results - Increased 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. Conclusion - This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

Background and Aims Calcimimetic therapy, including oral cinacalcet and intravenous (IV) etelcalcetide, is often used to control parathyroid hormone (PTH) levels in hemodialysis (HD) patients. In a head-to-head clinical trial, etelcalcetide was superior to cinacalcet on PTH reduction. Given that oral administration of cinacalcet is susceptible to challenges of self-management and adherence, etelcalcetide may be even more effective in the real-world setting. To limit confounding by indication, we used a facility calcimimetic preference approach to investigate the comparative effectiveness of etelcalcetide vs. cinacalcet by estimating effects on PTH and other mineral and bone disorder (MBD) markers in a cohort of US HD patients. Method We used data from the US Dialysis Outcomes and Practice Patterns Study (US-DOPPS), a prospective cohort study of in-center HD patients. During a 6-month run-in period from March to August 2019, we evaluated facility calcimimetic preference by calculating the proportion of calcimimetic users in each facility who were prescribed etelcalcetide (vs. cinacalcet). Among patients with any prescription for a calcimimetic during the 6-month run-in period, we evaluated MBD marker outcomes (PTH, albumin-corrected serum calcium [Ca], serum phosphorus [P]), averaged over the subsequent 6 months, from September 2019 to February 2020. We compared HD facilities that treated >75% of calcimimetic users with etelcalcetide (“Etel-first”) vs. those that treated >75% of calcimimetic users with cinacalcet (“Cina-first”). Linear regression was used to model each continuous outcome. Modified Poisson regression was used to estimate the prevalence ratio (PR) of each MBD marker being out of target (PTH >600 pg/mL, Ca 5.5 mg/dL). All models were adjusted for patient-level and facility-level confounders and accounted for facility clustering using GEE. Results We excluded 38 HD facilities with little-to-no calcimimetic use (600 was lower (PR=0.75; 95% CI: 0.60, 0.94) in adjusted models. The adjusted mean levels of serum Ca and serum P (secondary outcomes) were slightly lower in Etel-first (vs. Cina-first) facilities [Table 1]. Conclusion To our knowledge, this is the first large-scale comparison of IV etelcalcetide with oral cinacalcet in the real-world setting. Our unique approach resembles a natural experiment by leveraging practice variation across the US and isolating HD facilities with a clear preference for one calcimimetic. Thus, the prescribed calcimimetic type for included patients was more likely determined by facility preference than biased by patient indication. Our results indicate better PTH control (mean levels ∼100 pg/mL lower) in US HD facilities using etelcalcetide (vs. cinacalcet) as the primary calcimimetic therapy. Further research is needed to investigate the degree to which the greater real-world effectiveness of IV etelcalcetide (vs. oral cinacalcet) may be driven by adherence to the prescribed therapy, and how clinical outcomes may be affected.

This study aimed to investigate the association between adolescent overweight and obesity and PTC risk in adulthood. We conducted a case-control study in the Republic of Korea with 1,549 PTC patients and 15,490 controls individually matched for age and sex. We estimated body mass index (BMI) at age 18 years from self-reported weight at this age. Compared with BMI BRAFV600E mutation. Adolescent overweight and obesity was associated with higher risk of PTC in adulthood. Our results emphasise the importance of weight management in adolescence to decrease the PTC risk.

BackgroundReal-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS).MethodsThis was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD).ResultsOverall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C ConclusionsLDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.

PURPOSE This 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 METHODS A 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). RESULTS The 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. CONCLUSION The findings of this study suggest that a decreased GC-specific mortality and improved survival rate in GC patients can be achieved through GE screening.

Background Iodine excess has been suggested as an exogenous risk factor of papillary thyroid cancer (PTC). We performed a systematic review and meta-analysis to assess the relationship between iodine exposure measured in various forms and PTC prevalence. Methods We searched MEDLINE, Embase, and the Cochrane Library for case-control studies on iodine and PTC published up to December 2015. Exposure to iodine was compared between PTC and control groups. Results From the 16 selected studies, the odds ratio (OR) for the overall effect size between high iodine exposure and PTC risk was 1.418 (95% confidence interval [CI] 1.054-1.909). Based on 7 studies conducted in high iodinated regions, a positive association between iodine exposure and PTC was observed (OR 2.200; 95% CI 1.389-3.483). Conclusion This study demonstrated a higher exposure to iodine in patients with PTC compared with controls, especially for patients from high iodinated regions.

Objectives We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). Methods A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). Results Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for

Purpose: Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. Methods: Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. Results: Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p < 0.05). Longer daily smartphone use was associated with a higher likelihood of having multiple ocular symptoms (5–7 symptoms out of 7 symptoms; p = 0.005). Excessive/intermittent use (>2 hours daily and ≤2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (p = 0.001). Conclusion: Increasing exposure to smartphones can have a negative impact on ocular health in adolescents.

The importance of adherence to antihypertensive treatments for the prevention of cardiovascular disease has not been well elucidated. This study evaluated the effect of antihypertensive medication adherence on specific cardiovascular disease mortality (ischemic heart disease [IHD], cerebral hemorrhage, and cerebral infarction). Our study used data from a 3% sample cohort that was randomly extracted from enrollees of Korean National Health Insurance. Study subjects were aged ≥20 years, were diagnosed with hypertension, and started newly prescribed antihypertensive medication in 2003 to 2004. Adherence to antihypertensive medication was estimated as the cumulative medication adherence. Subjects were divided into good (cumulative medication adherence, ≥80%), intermediate (cumulative medication adherence, 50%–80%), and poor (cumulative medication adherence, P for trend=0.005), cerebral hemorrhage (hazard ratio, 2.19; 95% confidence interval, 1.28–3.77; P for trend=0.004), and cerebral infarction (hazard ratio, 1.92; 95% confidence interval, 1.25–2.96; P for trend=0.003) than those with good adherence. The estimated hazard ratios of hospitalization for cardiovascular disease were consistent with the mortality end point. Poor medication adherence was associated with higher mortality and a greater risk of hospitalization for specific cardiovascular diseases, emphasizing the importance of a monitoring system and strategies to improve medication adherence in clinical practice.

Purpose The Health and Prevention Enhancement (H-PEACE) study was designed to investigate the association of diagnostic imaging results, biomarkers and the predisease stage of non-communicable diseases (NCDs), such as malignancies and metabolic diseases, in an average-risk population in Korea. Participants This study enrolled a large-scale retrospective cohort at the Healthcare System Gangnam Center, Seoul National University Hospital, from October 2003 to December 2014. Findings to date The baseline and follow-up information collected in the predisease stage of NCDs allows for evaluation of an individual’s potential NCD risk, which is necessary for establishing personalised prevention strategies. A total of 91 336 health examinees were included in the cohort, and we repeatedly measured and collected information for 50.9% (n=46 484) of the cohort members. All participants completed structured questionnaires (lifestyle, medical history, mini-dietary assessment index, sex-specific variables and psychiatric assessment), doctors’ physical examinations, laboratory blood and urine tests and digital chest X-ray imaging. For participants with available data, we also obtained information on specific diagnostic variables using advanced diagnostic tests, including coronary CT for coronary calcium scores, colonoscopy and brain MRI. Furthermore, 17 455 of the participants who provided informed consent and donated blood samples were enrolled into the Gene-environmental interaction and phenotype study, a subcohort of the H-PEACE, from October 2013, and we analysed genome-wide single-nucleotide polymorphism array data for 6579 of these blood samples. Future plans The data obtained from this cohort will be used to facilitate advanced and accurate diagnostic techniques related to NCDs while considering various phenotypes. Potential collaborators can access the dataset after receiving approval from our institutional review board. Applications can be submitted on the study homepage (http://en-healthcare.snuh.org/HPEACEstudy).

Background The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups. Methods This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis. Results Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014). Conclusion The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Previous observational studies have suggested that metformin in diabetes patients may reduce breast cancer risk more than the reductions from other anti-diabetes medications. This randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of metformin for controlling physical and metabolic profiles related to prognosis and adverse events in non-diabetic breast cancer patients. Female breast cancer patients (N = 105), at least 6 months post-mastectomy, with obesity (≥25 kg/m(2)) and/or pre-diabetes (fasting blood sugar levels ≥100 mg/dL), were randomly assigned to three groups (placebo, metformin 500 mg, and metformin 1000 mg) stratified by tamoxifen use. A linear mixed model for repeated measurements among three groups and ANOVA for profile differences during 6 months of treatment were used for the intention-to-treat analysis. The metformin 1000 mg group had a significantly greater decline in glucose and HbA1c levels between treatment weeks 0 and 6 month (p = 0.008 and 0.009, respectively), and the declines increased with an increase in body mass index (BMI) level (p interaction with BMI = 0.007 and 0.067, respectively). A marginally significant different effect from the metformin 1000 mg treatment was detected for glucose and HbA1c levels (p interaction = 0.084 and 0.063, respectively) in the intention-to-treat analysis. Metformin 1000 mg treatment had a favorable effect on controlling glucose and HbA1C levels in obese non-diabetic breast cancer patients, indicating prognostic importance. Further trials are needed to elucidate the risk-benefit ratio of long-term use of metformin.

Aim. The incidence of thyroid cancer is increasing worldwide. The prevalence of type 2 diabetes mellitus (T2DM) is also increasing. Therefore, we aimed to analyze the effect of T2DM on thyroid cancer. Methods. A case-control study was performed. A total of 415 healthy controls with thyroid ultrasound screening and physician consultation were selected from the Thyroid Cancer Longitudinal Study (T-CALOS). Among patients with thyroid cancer who were enrolled in T-CALOS, 415 patients were matched to the control group according to age and sex. We assessed the effects of T2DM, T2DM duration, and T2DM medication on thyroid cancer. Results. Women with T2DM had lower odds of thyroid cancer than women without T2DM (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.20–0.81). Individuals receiving T2DM medication had higher odds of thyroid cancer compared to those without T2DM medication (OR: 5.21, 95% CI: 1.58–17.15). Individuals with T2DM duration Conclusions. Individuals with early T2DM are presumed to have a low incidence of thyroid cancer, and this effect seems to last up to 6 years after diagnosis of T2DM.

Sir,Mortazavi and co-authors have given two insightful comments on our paper “Association between Exposure to Smartphones and Ocular Health in Adolescents,” which we examined thoroughly. We appreci...

Supplemental Digital Content is available in the text, We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors. Using matched case–control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes. The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%–69.8%]; luminal B, 21.4% [95% CI = 18.6–24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%–74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%–32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (P heterogeneity ≤ 0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and −3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; P heterogeneity ≤ 0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (P heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, −3.1%; P heterogeneity ≤ 0.001). Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.

Supplemental Digital Content is available in the text, We evaluated the association between weight change in middle-aged adults and papillary thyroid cancer (PTC) based on a large-scale case-control study. Our study included data from 1551 PTC patients (19.3% men and 80.7% women) who underwent thyroidectomy at the 3 general hospitals in Korea and 15,510 individually matched control subjects. The subjects’ weight history, epidemiologic information, and tumor characteristics confirmed after thyroidectomy were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined for the annual average changes in weight and obesity indicators (body mass index (BMI), body surface area, and body fat percentage (BF%) in subjects since the age of 35 years. Subjects with a total weight gain ≥10 kg after age 35 years were more likely to have PTC (men, OR, 5.39, 95% CI, 3.88–7.49; women, OR, 3.36, 95% CI, 2.87–3.93) compared with subjects with a stable weight (loss or gain

Context: Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. Objective: This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. Design: This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. Patients: A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. Main Outcome Measure: Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. Results: RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22–1.06) when a 2-year latency period was accounted for. High-dose RAI (≥120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05–0.62) in the cohort with a 2-year latency period. Conclusions: The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer.

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 (X7 times a week), and binge drinking (X55 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.

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

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 ( 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.

Introduction Thyroid cancer incidence in Korea is the highest in the world and has recently increased steeply. However, factors contributing to this sudden increase have not been fully elucidated, and few studies have explored the postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was initiated with three aims: (1) to identify factors predicting quality of life, recurrence, and incidence of other diseases after thyroid cancer treatments; (2) to investigate environmental exposure to radiation, toxicants and molecular factors in relation to tumour aggressiveness; and (3) to evaluate gene–environment interactions that increase thyroid cancer in comparison with healthy participants from a pool of nationwide population-based healthy examinees. Methods and analysis T-CALOS enrols patients with incident thyroid cancer from three general hospitals, Seoul National University Hospital, Seoul National University Bundang Hospital and National Medical Center, Korea. The study is an ongoing project expecting to investigate 5000 patients with thyroid cancer up until 2017. Healthy examinees with a normal thyroid confirmed by sonography have been enrolled at the Healthy Examination Center at Seoul National University Hospital. We are also performing individual matching using two nationwide databases that are open to the public. Follow-up information is obtained at patients’ clinical visits and by linkage to the national database. For statistical analysis, we will use conditional logistic regression models and a Cox proportional hazard regression model. A number of stratifications and sensitivity analyses will be performed to confirm the results. Ethics and dissemination Based on a large sample size, a prospective study design, comprehensive data collection and biobank, T-CALOS has been independently peer-reviewed and approved by the three hospitals and two funding sources (National Research Foundation of Korea and Korean Foundation for Cancer Research). The results of T-CALOS will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

BACKGROUND: Incidence of thyroid cancer has been rapidly increased, in not only small sizes with improved detection devices but also large size of tumors whose underlying mechanisms remain unclear. Body size and weight change in adulthood were examined as the potential risk factors for thyroid cancer development. METHODS: A large scale case-control study was conducted with constructed questionnaire for their height, weight (current, 2 years ago, at the age of 20 and 35 years old) and confounders. Medical charts were reviewed for cancer histology, tumor aggressiveness and BRAF mutation status. A total of 2,003 cases (1,611 females and 392 males) and individually matched 17,700 controls (13,983 females and 3,717 males) by age, sex, 12-year education and birth year were included. Logistic regression model were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Having a tall height and heavy weight was associated with increased risk in both females [OR and 95%CI for height and weight: 1.46 (1.25-1.71) and 2.66 (2.24-3.15), respectably] and males [OR and 95%CI for height and weight: 1.71 (1.25-2.34) and 2.80 (2.00-3.92), respectably] compared to those in the lowest quartile for the body sizes. This study observed approximated tripled the risk of thyroid cancer [OR and 95%CI: 3.03 (2.10-4.37)] when female subjects gained 10kg or more within recent 2 years. Males who gained 10 kg or more after 35 years old were more likely to have a greater tumor size [ CONCLUSION: The results support plausible hormonal and metabolic factors related height, weight, and rapid weight gain in adulthood increase thyroid carcinogenesis. Citation Format: Yunji Hwang, Kyu-Eun Lee, Young Joo Park, Do Joon Park, Yeo-Kyu Youn, Yohwan Yeo, Seung-Hyun Ma, Daehee Kang, Keun-Young Yoo, Sue K. Park. Height, weight and weight changes during adulthood and thyroid cancer risk. [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 2163. doi:10.1158/1538-7445.AM2014-2163