Purpose
New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.
Materials and Methods
Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.
Results
During a median follow-up of 14.5 years, 166 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 35.2% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval 0.99-1.98). In contrast, the results for other nomenclature were not significant.
Conclusion
Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.
Youjin Hong, Soseul Sung, Woojin Lim, Sungji Moon, Kwang-Pil Ko, Jung Eun Lee, Inah Kim, Sun Ha Jee, Sun-Seog Kweon, Min-Ho Shin, Sangmin Park, Seung-Ho Ryu, Sun Young Yang, Jeongseon Kim, Sang-Wook Yi, Yoon-Jung Choi, Jeong-Soo Im, Hong Gwan Seo, Sue K. Park
Received July 26, 2024 Accepted November 18, 2024 Published online November 19, 2024
Purpose
Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. IARC designated as Group 1 and Group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030.
Materials and Methods
The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin’s formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks (RRs), which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis.
Results
The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. EP combined HRT accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors.
Conclusion
Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.
Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang
Cancer Res Treat. 2025;57(1):198-211. Published online July 26, 2024
Purpose The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.
Purpose We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns.
Materials and Methods The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed.
Results In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10–83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10–6 (0.05/13,114); DEFB108B had the lowest p=5.94×10–15, followed by FAM86C1 (p=1.74×10–14), PSCA (p=1.81×10–14), and KLHDC4 (p=5.00×10–10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway.
Conclusion While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.
Citations
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Purpose
Obesity has been determined to be associated with fat mass and obesity-associated (FTO) gene and thyroid cancer risk. However, the effect of combined interactions between obesity and the FTO gene on thyroid cancer needs further investigation. This study aimed to examine whether interactions between body mass index (BMI) and the FTO gene are associated with an increased risk of thyroid cancer.
Materials and Methods
A total of 705 thyroid cancer cases and 705 sex- and age-matched normal controls were selected from the Cancer Screenee Cohort in National Cancer Center, Korea. A conditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the measure of associations and the combined effect of BMI and FTO gene on thyroid cancer.
Results
BMI was associated with an increased risk of thyroid cancer in subclasses of overweight (23-24.9 kg/m2; adjusted OR, 1.50; 95% CI, 1.12 to 2.00) and obese (≥ 25 kg/m2) (adjusted OR, 1.62; 95% CI, 1.23 to 2.14). There were positive associations between the FTO genetic variants rs8047395 and rs8044769 and an increased risk of thyroid cancer. Additionally, the combination of BMI subclasses and FTO gene variants was significantly associated with thyroid cancer risk in the codominant (rs17817288), dominant (rs9937053, rs12149832, rs1861867, and rs7195539), and recessive (rs17817288 and rs8044769) models.
Conclusion
Findings from this study identified the effects of BMI on thyroid cancer risk among individuals carrying rs17817288, rs9937053, rs12149832, rs1861867, rs7195539, and rs8044769, whereas the effects of BMI may be modified according to individual characteristics of other FTO variants.
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Purpose
Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.
Materials and Methods
In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.
Results
Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.
Conclusion
Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals’ genetic risk.
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Purpose
Half of the world’s gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer.
Materials and Methods
We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls.
Results
We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer.
Conclusion
Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.
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Purpose
Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings.
Materials and Methods
This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT.
Results
After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined.
Conclusion
Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.
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Purpose
The current study investigated whether the combined effects of soy intake and genetic polymorphisms of interleukin (IL) genes modify gastric cancer risk.
Materials and Methods
A total of 377 cases and 754 controls of Korean origin were included in the analysis. Soy consumption was assessed using a semi-quantitative food frequency questionnaire. Seven variants of IL10 (rs1800871), IL2 (rs2069763 and rs2069762), IL13 (rs6596090 and rs20541), and IL4R(rs7205663 and rs1805010) were genetically analyzed. To analyze the combined effect of soy intake and genetic polymorphisms, a low-intake group and high-intake group of each type of soy were categorized based on the intake level of the control group. Interactions between soy products and these genetic variants were analyzed by a likelihood ratio test, in which a multiplicative interaction term was added to the logistic regression model.
Results
A higher intake of nonfermented soy products was associated with a reduced cancer risk (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.43 to 0.90), and the reduced risk was only apparent in males (OR, 0.44; 95% CI, 0.27 to 0.71). None of the IL genetic polymorphisms examined were independently associated with gastric cancer risk. Individuals with a minor allele of IL2 rs2069762 and a higher intake of nonfermented soy food had a decreased risk of gastric cancer (OR, 0.46; 95% CI, 0.31 to 0.68) compared to those with a lower intake (pinteraction=0.039).
Conclusion
Based on the genetic characteristics of the studied individuals, the interaction between IL2 rs2069762 and nonfermented soy intake may modify the risk of gastric cancer.
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Purpose Although the incidence of thyroid cancer in Korea has rapidly increased over the past decade, few studies have investigated its risk factors. This study examined the risk factors for thyroid cancer in Korean adults.
Materials and Methods The study design was a hospital-based case-control study. Between August 2002 and December 2011, a total of 802 thyroid cancer cases out of 34,211 patients screened from the Cancer Screenee. Cohort of the National Cancer Center in South Korea were included in the analysis. A total of 802 control cases were selected from the same cohort, and matched individually (1:1) by age (±2 years) and area of residence for control group 1 and additionally by sex for control group 2.
Results Multivariate conditional logistic regression analysis using the control group 1 showed that females and those with a family history of thyroid cancer had an increased risk of thyroid cancer, whereas ever-smokers and those with a higher monthly household income had a decreased risk of thyroid cancer. On the other hand, the analysis using control group 2 showed that a family history of cancer and alcohol consumption were associated with a decreased risk of thyroid cancer, whereas higher body mass index (BMI) and family history of thyroid cancer were associated with an increased risk of thyroid cancer.
Conclusion These findings suggest that females, those with a family history of thyroid cancer, those with a higher BMI, non-smokers, non-drinkers, and those with a lower monthly household income have an increased risk of developing thyroid cancer.
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Purpose
Epidemiological studies have demonstrated an association between excessive salt intake and gastric cancer risk, and this potential risk increases the need for adequate gastric cancer screening in individuals with high salt intake. However, the association between salt intake and gastric cancer screening in the general population has rarely been investigated. We explored the association between salt preference and participation in gastric cancer screening among a nationally representative Korean population.
Materials and Methods
The study population was derived from the Korean National Cancer Screening Survey (KNCSS) 2006-2007, an annual nationwide interview survey investigating cancer screening rates. Of 4,055 individuals who participated in the KNCSS 2006-2007, 3,336 individuals aged over 40 years were included in our analysis. The odds ratio (OR) and 95% confidence interval (CI) were estimated using polytomous logistic regression.
Results
Individuals with higher salt preference were less likely to participate in regular gastric cancer screening. After adjusting for age, sex, monthly household income, education, family history of cancer, and self-rated health status, ORs for undergoing regular gastric cancer screening were 1.00, 0.82 (95% CI, 0.61 to 1.12), 0.74 (95% CI, 0.54 to 1.00), 0.77 (95% CI, 0.56 to 1.05), and 0.38 (95% CI, 0.16 to 0.92) according to the level of salt preference (p for trend=0.048).
Conclusion
Individuals with higher salt preference showed suboptimal gastric cancer screening adherence compared to those with a lower salt preference. These findings highlight the need for better delivery of educational messages to change risk perceptions regarding gastric cancer screening practice.
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The Science of Salt: A focused review on salt‐related knowledge, attitudes and behaviors, and gender differences Briar McKenzie, Joseph Alvin Santos, Kathy Trieu, Sudhir Raj Thout, Claire Johnson, JoAnne Arcand, Jacqui Webster, Rachael McLean The Journal of Clinical Hypertension.2018; 20(5): 850. CrossRef
Jungnam Joo, Kyong-Ah Yoon, Tomonori Hayashi, Sun-Young Kong, Hye-Jin Shin, Boram Park, Young Min Kim, Sang-Hyun Hwang, Jeongseon Kim, Aesun Shin, Joo-Young Kim
Cancer Res Treat. 2016;48(2):708-714. Published online June 22, 2015
Purpose
Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer.
Materials and Methods
Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed.
Results
The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type.
Conclusion
The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.
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PURPOSE Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. MATERIALS AND METHODS We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. RESULTS TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64).
In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. CONCLUSION The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.
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PURPOSE Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes. MATERIALS AND METHODS This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method. RESULTS Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022). CONCLUSION We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.
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PURPOSE This study was conducted in order to demonstrate changing trends in colorectal cancer incidence according to sex, age group, and anatomical location in the Korean population. MATERIALS AND METHODS Data from the Korea Central Cancer Registry between 1999 and 2009 were analyzed. Annual percent changes (APCs) of sex- and age-specific incidence rates for cancer of the proximal colon (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] code C18.0-18.5), distal colon (C18.6-18.7), and rectum (C19-20), and male-to-female incidence rate ratios (IRR) were calculated. RESULTS The age-standardized incidence rate (ASR) of colorectal cancer was 27 (per 100,000) in 1999 and increased to 50.2 in 2009 among men (APC, 6.6%). The ASR for women was 17.2 in 1999 and 26.9 in 2009 (APC, 5.1%). The rectum was the most common site of cancer among both men and women during 1999 and 2009. However, the distal colon had the highest APC (10.8% among men and 8.4% among women), followed by the proximal colon (7.9% among men and 6.6% among women), and rectum (5.2% among men and 2.4% among women). The proportion of rectal cancer decreased from 51.5% in 1999 to 47.1% in 2009 among men, and from 50.5% to 42.8% among women. An increase in the male-to-female IRR was observed for distal colon cancer and rectal cancer, whereas the IRR for proximal colon cancer was stable. CONCLUSION The rapid increase in colorectal cancer incidence is mainly attributed to the increase in colon cancer, especially distal colon cancer, and may be explained by a transition of risk factors for subsites or by the effect of colorectal cancer screening.
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