Genetically predicted dietary intake and risks of colorectal cancer: a Mendelian randomisation study.

BACKGROUND: Effects of confounders on associations between diet and colorectal cancer (CRC) in observational studies can be minimized in Mendelian randomization (MR) approach. This study aimed to investigate observational and genetically predicted associations between dietary intake and CRC using one-sample MR. METHODS: Using genetic data of over 93 million variants, we performed a genome-wide association study to find genomic risk loci associated with dietary intake in participants from the UK Biobank. Then we calculated genetic risk scores of diet-related variants and used them as instrumental variables in the two-stage least square MR framework to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations. We also performed observational analyses using age as a time-scale in Cox proportional hazard models. RESULTS: Allele scores were calculated from 399 genetic variants associated with the consumption of of red meat, processed meat, poultry, fish, milk, cheese, fruits, vegetables, coffee, tea, and alcohol in participants from the UK Biobank. In MR analysis, genetically predicted fruit intake was significantly associated with a 21% decreased risk of CRC (HR = 0.79, 95% CI = 0.66-0.95), and there was a marginally inverse association between vegetable intake and CRC (HR = 0.85, 95% CI = 0.71-1.02). However, null findings were observed in multivariable analysis, with HRs (95% CIs) of 0.99 (0.98-1.01) and 0.99 (0.98-1.00) per increment of daily servings of fruits and vegetables, respectively. CONCLUSION: Dietary habits were attributable to genetic variations, which can be used as instrumental variables in the MR framework. Our study supported a causal relationship between fruit intake and a decreased risk of CRC and suggested an effective strategy of consuming fruits in the primary prevention of CRC.

Impact of body mass index and waist-to-hip ratio on mortality in middle-aged Koreans: A prospective cohort study based on a Health Examinees study.

Objectives: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. Methods: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. Results: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both men and women with BMIs of less than 21 kg/m2 and greater than or equal to 30 kg/m2 are at increased risk. The results showed that men with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted HR: 2.24 [95% CI: 1.73-2.91]) and cardiovascular mortality (2.27 [1.23-4.20]). Similarly, men with a WHR of less than 0.80 (1.38 [1.08-1.77]), 0.90 to less than 0.95 (1.15 [1.02-1.29]), and greater than or equal to 0.95 (1.28 [1.11-1.47]) showed an increased risk of all-cause mortality. In women, a BMI of less than 18 kg/m² was linked to a higher risk of cardiovascular mortality (2.67 [1.13-6.33]). Conclusion: Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in men who were slightly overweight with a BMI of 23-25 kg/m2.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 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). 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 (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. 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.

Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank.

Importance: Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome. Objectives: To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC. Design, Setting, and Participants: This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021. Exposures: The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained. Main Outcomes and Measures: Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses. Results: A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10-5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP). Conclusions and Relevance: In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Sleep Duration, Comorbidities, and Mortality in Korean Health Examinees: A Prospective Cohort Study.

OBJECTIVES: The association between long sleep duration and mortality is frequently attributed to the confounding influence of comorbidities. Nevertheless, past efforts to account for comorbidities have yielded inconsistent outcomes. The objective of this study was to evaluate this relationship using a large prospective cohort in Korea. METHODS: The study included 114 205 participants from the Health Examinees Study, who were followed for a median of 9.1 years. A composite comorbidity score was developed to summarize the effects of 21 diseases. Using Cox proportional hazards regression, hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and cardiovascular mortality associated with sleep duration were estimated. These estimates were adjusted for socio-demographic factors, lifestyle factors, body mass index, and comorbidity score. Additionally, a stratified analysis by subgroups with and without comorbidities was conducted. RESULTS: Throughout the follow-up period, 2675 deaths were recorded. After all adjustments, an association was observed between a sleep duration of 8 hours or more and all-cause mortality (HR, 1.10; 95% CI, 1.01 to 1.20). However, no such association was detected in the stratified analysis for the subgroups based on comorbidity status. CONCLUSIONS: Long sleep duration was found to be associated with all-cause mortality among Koreans, even after adjusting for comorbidities. Additional studies are required to explore the mechanism underlying the association between sleep duration and major causes of mortality.

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank.

BACKGROUND: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. METHODS: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. RESULTS: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores). CONCLUSION: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Reproductive Factors and Endometrial Cancer Risk Among Women.

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries. Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk. Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023. Exposures: Reproductive factors were assessed using a questionnaire in each cohort. Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs. Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk. Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research and Korean Cancer Prevention Guidelines and cancer risk: a prospective cohort study from the Health Examinees-Gem study.

OBJECTIVES: The purpose of this study was to explore the association between adherence to 2 cancer prevention recommendations and cancer risk. METHODS: In total, 104,386 individuals aged 40-69 years old who were recruited between 2004 and 2013 in the Health Examinees-Gem study were included. Adherence scores were constructed based on 8 items from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, including body weight, physical activity, diet, alcohol consumption and breastfeeding, and on 6 items from the Korean cancer prevention guidelines (smoking status, eating vegetables and fruits, salty foods, alcohol intake, physical activity, and body weight). A Cox proportional hazards model was used to estimate the associations between adherence scores and the risk of total and 5 major cancers. RESULTS: The multivariable hazard ratio (HR) for total cancer with the high adherence score versus the lowest score (4.25-7.00 vs. 0.00-3.25) for the WCRF/AICR guidelines was 0.91 (95% confidence interval [CI], 0.82 to 1.00) in men. A reduced breast cancer risk was observed among women with the highest score. Men within the highest category of the Korean cancer prevention guideline score (3.25-6.00) had an HR of 0.80 (95% CI, 0.73 to 0.88) for developing total cancer compared to men within the lowest score (0.00-2.50). The higher adherence group among men showed lower risks of developing stomach, colorectal, and lung cancers. CONCLUSIONS: Adhering to guidelines for cancer prevention can help to reduce the risk of developing cancer in Korean men. The association might differ by cancer type and gender.

Impact of pre- and post-diagnosis physical activity on the mortality of patients with cancer: Results from the Health Examinees-G study in Korea.

BACKGROUND: Physical activity (PA) is recommended to improve the survival of cancer patients. However, the prognostic impact of specific PAs is not well understood. Therefore, we investigated the associations of the duration, type, intensity, and number of PAs one participates in pre- and post-diagnosis with mortality in Korean patients with cancer. METHODS: Among the participants aged 40-69 years recruited from the Health Examines study, those diagnosed with cancer after baseline (n = 7749) and within 10 years before baseline (n = 3008) were included in the analyses for pre- and post-diagnosis PA, respectively. Duration, intensity, type, and number of leisure-time physical activities participated in were assessed using questionnaires. The Cox proportional hazard model was used to characterize the association between PA and cancer-specific mortality, adjusting for demographics, behaviors, comorbidities, and cancer stage based on the Surveillance, Epidemiology, and End Results program. RESULTS: Pre-diagnosis, patients participating in vigorous-intensity activities (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.61-0.82), walking (HR: 0.85, 95% CI: 0.74-0.97), climbing (HR: 0.65, 95% CI: 0.55-0.77), sports (HR: 0.39, 95% CI: 0.25-0.61), and more than two activities (HR: 0.73, 95% CI: 0.63-0.86) had significantly lower all-cause mortality. Importantly, these associations were only found in patients with colorectal cancer participating in vigorous-intensity activities (HR: 0.40, 95% CI: 0.23-0.70). Post-diagnosis, only patients who performed more than two activities (HR: 0.65, 95% CI: 0.44-0.95) had significantly lower all-cause mortality. Similar associations were found for cancer mortality, both pre- and post-diagnosis. CONCLUSION: Specific characteristics of PA pre- and post-diagnosis may influence the survival of cancer patients.

Associations between Physical Activity and Incidence of Cancer among Overweight Adults in Korea: Results from the Health Examinees-G Study.

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 [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. PREVENTION RELEVANCE: Overall cancer risk is associated with leisure-time physical activity such as duration, intensity, type, and diversity in overweight males, but not in the general population. The decreased risk was most noticeable for colorectal cancer. Our results suggest that physical activity may reduce the risk of cancer among overweight Asian males.

Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study.

BACKGROUND: Previous studies suggested that metabolic syndrome (MetS) might create a pro-cancer environment and increase cancer incidence. However, evidence on the risk of gastric cancer (GC) was limited. This study aimed to evaluate the association between MetS and its components and GC in the Korean population. METHODS: Included were 108,397 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem study during 2004-2017. The multivariable Cox proportional was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between MetS and its components with GC risk. Age was used as the time scale in the analyses. The stratified analysis was performed to determine the joint effect of lifestyle factors and MetS on GC risk in different groups. RESULTS: During the mean follow-up of 9.1 years, 759 cases of newly diagnosed cancer (408 men and 351 women) were identified. Overall, participants with MetS had a 26% increased risk of GC than those without MetS (HR 1.26; 95% CI 1.07-1.47); the risk increased with the number of MetS components (p for trend 0.01). Hypertriglyceridemia, low HDL-cholesterol, and hyperglycemia were independently associated with the risk of GC. The potential joint effect of MetS and current smokers (p for interaction 0.02) and obesity (BMI ≥ 25.0) (p for interaction 0.03) in GC. CONCLUSIONS: In this prospective cohort study, we found that MetS were associated with an increased risk of GC in the Korean population. Our findings suggest that MetS may be a potentially modifiable risk factor for GC risk.