Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017

Lou, Lixia; Wang, Linyan; Zhang, Yaoyi; Chen, Guofeng; Lin, Lele; Jin, Xiaoli; Huang, Yi; Chen, Jian

doi:10.1136/bmjopen-2019-033323

Cited by 67 publications

(60 citation statements)

References 32 publications

(37 reference statements)

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“…Thirdly, the improvement of socioeconomic status [7,8,20,24] and the advancement of medical technology and treatment [3] might contribute to a decline in the GC burden and also cause differences in the changing trends of GC burden in different regions and countries. Moreover, corresponds to other research reports [2,9,12], the GC burden in males was much higher than that in females, and this difference increased with age and reached a peak in the 50-69 age group. Males first have more opportunities to be exposed to occupational and environmental risk factors [5,22].…”

Section: Discussionsupporting

confidence: 91%

“…Many studies have evaluated the GC burden at the global, regional, and national levels [2,7,9,12], however, the GC burden of different sexes and age-specific groups remains unknown. In this study, based on the latest database of the Global Burden of Diseases (GBD) study (2019), we comprehensively evaluated the global changing trends of GC incidence and mortality.…”

Section: Introductionmentioning

confidence: 99%

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Global changing trends in incidence and mortality of gastric cancer by age and sex, 1990-2019: Findings from Global Burden of Disease Study

Zhang¹,

Chen²,

Zhang³

et al. 2021

J. Cancer

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Background:The global disease burden of gastric cancer (GC) is still heavy. Understanding the patterns and trends of the global GC burden is important for developing precise prevention strategies. Materials and Methods:The data of GC burden were retrieved from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of the age-standardized incidence and mortality rates (ASIR and ASMR) of global GC by age-specific groups (15-49, 50-69, and ≥70 years), sexes, socio-demographic indexes (SDIs), regions, and countries. Results: In 2019, the ASIR and ASMR of global GC increased with age in both sexes, and reached a peak in the older 70 age group. The ASIR and ASMR in males were higher than those in females. From 1990 to 2019, the global number of GC incident cases increased in both sexes in all age-specific groups; while the ASIR of GC decreased, and the most significant decrease was observed in the 50-69 age group [males: EAPC=-1.34, 95% CI: (-1.49, -1.18); females: EAPC= -2.09, 95% CI: (-2.22, -1.96)]. During the study period, downward trends in ASIR of GC were observed in both sexes in most SDI regions, GBD regions, and countries. Similar trends in ASMR of GC were also observed. Conclusion:The global GC incidence and mortality rates decreased from 1990 to 2019 in both sexes, most GBD regions, and most countries. However, the GC burden was still heavy in some GBD regions and countries in special age-specific groups. It is important to formulate and implement tertiary prevention strategies based on the GC burden of age-specific groups in different regions and countries.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Global changing trends in incidence and mortality of gastric cancer by age and sex, 1990-2019: Findings from Global Burden of Disease Study

Zhang¹,

Chen²,

Zhang³

et al. 2021

J. Cancer

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“…To identify statins’ pleiotropic effects, previous studies have used genetically mimicked statins to assess statins’ metabolomic profile [ 13 ], compared it with that of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors [ 14 ], and compared statin’s lipoprotein signature with that of cholesteryl ester transfer protein (CETP) inhibitors [ 15 ]. However, none of these studies has been comprehensive across the phenotype or sex-specific, when differences by sex are evident for the incidence of CVD [ 16 ] and some cancers [ 17 , 18 ], highlighting the possibility of sex-specific pathways and sex-specific impacts. To fill this gap, we conducted a phenome-wide association study (PheWAS), a summary statistics-based [ 19 ] genotype-to-phenotype approach [ 20 , 21 ], to assess systematically the sex-specific associations of genetically mimicking statins with a wide range of conditions and related phenotypes, using the largest available genome-wide association studies (GWAS), with validation where possible.…”

Section: Introductionmentioning

confidence: 99%

A phenome-wide association study of genetically mimicked statins

Schooling

2021

BMC Med

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Background Beyond their success in cardiovascular disease prevention, statins are increasingly recognized to have sex-specific pleiotropic effects. To gain additional insight, we characterized associations of genetically mimicked statins across the phenotype sex-specifically. We also assessed whether any apparently non-lipid effects identified extended to genetically mimicking other widely used lipid modifiers (proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) or were a consequence of low-density lipoprotein cholesterol (LDL-c). Methods We performed a sex-specific phenome-wide association study assessing the association of genetic variants in HMGCR, mimicking statins, with 1701 phenotypes. We used Mendelian randomization (MR) to assess if any non-lipid effects found were evident for genetically mimicked PCSK9 inhibitors and ezetimibe or for LDL-c. Results As expected, genetically mimicking statins was inversely associated with LDL-c, apolipoprotein B (ApoB), and total cholesterol (TC) and positively associated with glycated hemoglobin (HbA1c) and was related to body composition. Genetically mimicking statins was also inversely associated with serum calcium, sex hormone-binding globulin (SHBG), and platelet count and positively associated with basal metabolic rate (BMR) and mean platelet volume. Stronger associations with genetically mimicked statins were evident for women than men for lipid traits (LDL-c, ApoB, and TC), calcium, and SHBG, but not for platelet attributes, body composition, or BMR. Genetically mimicking PCSK9 inhibitors or ezetimibe was also associated with lower lipids, but was not related to calcium, SHBG, BMR, or body composition. Genetically higher LDL-c increased lipids and decreased BMR, but did not affect calcium, HbA1c, platelet attributes, or SHBG with minor effects on body composition. Conclusions Similar inverse associations were found for genetically mimicking statins on lipid traits in men and women as for other lipid modifiers. Besides the positive associations with HbA1c, BMI (which may explain the higher BMR), and aspects of body composition in men and women, genetically mimicking statins was additionally associated with platelet attributes in both sexes and was inversely associated with serum calcium and SHBG in women. This genetic evidence suggests potential pathways that contribute to the effects of statins particularly in women. Further investigation is needed to confirm these findings and their implications for clinical practice.

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“…Gender was also an important factor affecting the development of cancers ( Li et al, 2019 ; Lou et al, 2020 ). When stratified by gender, our data shows that individuals with the C7 rs1061429 AA genotype have an increased risk of gastric cancer in both men and women, but the risk in women is significantly higher than that in men.…”

Section: Discussionmentioning

confidence: 99%

Functional genetic variants in complement component 7 confer susceptibility to gastric cancer

Wang

Xie

et al. 2022

PeerJ

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Background Complement system plays an important role in innate immunity which involved in the changes tumor immune microenvironment by mediating the inflammatory response. This study aims to explore the relationship between complement component 7 (C7) polymorphisms and the risk of gastric cancer (GC). Materials and Methods All selected SNPs of C7 were genotyped in 471 patients and 471 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional Logistic regression to analyze the relationship between each genotype and the genetic susceptibility to gastric cancer. The level of C7 expression in GC was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and detected by Enzyme Linked Immunosorbent Assay. Kaplan–Meier plotter were used to reveal C7 of prognostic value in GC. We examined SNPs associated with the expression of C7 using the GTEx database. The effect of C7 polymorphisms on the regulatory activity of C7 was detected by luciferase reporter assay. Results Unconditional logistic regression showed that individuals with C7 rs1376178 AA or CA genotype had a higher risk of GC with OR (95% CI) of 2.09 (1.43–3.03) and 1.88 (1.35–2.63), respectively. For C7 rs1061429 C > A polymorphism, AA genotype was associated with the elevated risk for developing gastric cancer (OR = 2.16, 95% CI [1.37–3.38]). In stratified analysis, C7 rs1376178 AA genotype increased the risk of GC among males (OR = 2.88, 95% CI [1.81–4.58]), but not among females (OR = 1.06, 95% CI [0.55–2.06]). Individuals carrying rs1061429 AA significantly increased the risk of gastric cancer among youngers (OR = 2.84, 95% CI [1.39–5.80]) and non-smokers (OR = 2.79, 95% CI [1.63–4.77]). C7 was overexpressed in gastric cancer tissues and serum of cancer patients and was significantly associated with the prognosis. C7 rs1061429 C > A variant contributed to reduced protein level of C7 (P = 0.029), but rs1376178 didn’t. Luciferase reporter assay showed that rs1376178C-containing plasmid exhibited 2.86-fold higher luciferase activity than rs1376178 A-containing plasmid (P < 0.001). We also found that rs1061429A allele contributed 1.34-fold increased luciferase activity than rs1061429C allele when co-transfected with miR-591 (P = 0.0012). Conclusions These findings highlight the role of C7 in the development of gastric cancer.

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Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017

Cited by 67 publications

References 32 publications

Global changing trends in incidence and mortality of gastric cancer by age and sex, 1990-2019: Findings from Global Burden of Disease Study

Global changing trends in incidence and mortality of gastric cancer by age and sex, 1990-2019: Findings from Global Burden of Disease Study

A phenome-wide association study of genetically mimicked statins

Functional genetic variants in complement component 7 confer susceptibility to gastric cancer

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