Lancet Oncol: 100,000 people, 10 years of follow-up! Is the incidence of stomach cancer related to genetic and healthy lifestyle geometry?

China has one of the highest incidences of stomach cancer, which accounts for more than 40% of all cases worldwide.
In October 2020, a team of shen Hongbing academicians from Nanjing Medical University published a major paper entitled "Genetic Load, Healthy Lifestyle and Risk of Gastric Cancer - Based on Genome-Wide Integration Analysis and China's Large Prospective Cohort Study" in the international authoritative journal The Lancet Oncology.
this study is the largest Chinese-group gastric cancer whole genome association study (GWAS) to date (cumulative 10,254 gastric cancer cases and 10,914 cancer-free controls), the researchers based on genetic association results to build Chinese group gastric cancer The multi-gene genetic risk score (PRS) model, based on which more than 100,000 subjects of the China Chronic Disease Prospective Research Cohort (CKB) were applied, evaluated the relationship between PRS and gastric cancer risk, as well as the protective effect of healthy lifestyle on stomach cancer under different genetic loads.
results suggest that in Chinese groups, different gene spectrums are significantly associated with different risks of developing stomach cancer, and lifestyle significantly affects the risk of primary stomach cancer.
01 intriguing research design of this meta-analysis and forward-looking cohort study using two-stage research design.
phase of the study was designed using case-controlled studies, using data from six independent GHUAS data sets to perform a fixed-effect meta-analysis of the correlation between genetic variation and stomach cancer.
data set covered 21,168 Han individuals, of whom 10,254 had stomach cancer and 10,914 were matching control groups.
analysis, the researchers identified 764 gene variants from about 7 million gene variants that were significantly associated with gastric cancer risk, and constructed five multigene risk scores for gastric cancer with different significant thresholds (p-5×10? 539 SNP, p-5 × 10?? 112 SNP, p-5 × 10?? 38 SNP, p-5 × 10?? 18 SNP, p-5 × 10?? (12 SNPs)).
in the second phase of the validation process, the researchers conducted a forward-looking follow-up of more than 10 years in an independent, national, forward-looking cohort study, The China Chronic Disease Prospective Study (CKB), to evaluate the effectiveness of multigene risk scores and the effects of healthy lifestyles on stomach cancer risk.
design and workflow 02PRS can predict the risk of stomach cancer in a forward-looking and stable way by genotypeing a total of 100,220 subjects from the CKB queue and incorporating them into the final analysis.
study found that the above five gastric cancer PRS models were significantly related to the risk of stomach cancer, of which 112 single nucleotide polymorphism (SNP)-based PRS (SNP) and gastric cancer risk were the most significant, so this study used this scoring model as the main quantitative index to evaluate the genetic load of gastric cancer in groups Chinese.
according to the five-point spacing of PRS-112, the subjects were divided into Q1-Q5 categories, and with the increase of genetic load, the risk of stomach cancer increased significantly in individuals and showed a dose-reactive relationship (Figure A).
When the population with low, medium and high genetic risk was defined by Q1, Q2-Q4 and Q5 respectively, it was found that there was a significant difference in the cumulative standardization of gastric cancer incidence in three populations, and the risk of gastric cancer in the population with the lowest genetic risk increased by 54% compared to the 20% population with the lowest genetic risk (HR=1.54 (95% CI 1.22-1.94), p s 2.67 × 10?? The risk of stomach cancer increased by 108% in the 20% population with the highest genetic risk (2.08 (1.61-2.69), p .lt; 0.0001) (Figure B).
in the CKB cohort, the researchers defined healthy lifestyles based on four lifestyle habits, including not smoking (not smoking or quitting smoking for more than 15 years), not drinking alcohol (not drinking alcohol or drinking less than a month in the past year), eating less pickled vegetables (≤4 days/week), and regularly eating fresh fruits and vegetables.
at the same time to do the above 4 points, classified as lifestyle health, do the above 2-3 points, classified as lifestyle in general, can only do one of them or even completely can not do, classified as poor lifestyle.
increased with unhealthy lifestyle factors, the risk of stomach cancer increased significantly in individuals and showed a dose-reactive relationship (Figure C).
the risk of stomach cancer increased by 34% (HR=1.34, 95% CI: 1.00-1.81) and 103% (HR=2.03, 95% CI: 1.46-2.83) (Figure D) compared to those with healthy lifestyles.
-forward evaluation of lifestyle and risk of stomach cancer is worth mentioning that this effect is almost unaffected by the genetic load, nor is it affected by the genetic effect, reflecting the independent effect of the two in the process of gastric cancer.
the combined effect of genetic load and lifestyle in the occurrence of stomach cancer 04 Healthy lifestyle and gastric cancer risk negative correlation researchers analysis shows that in different genetic risk groups, adopting a healthy lifestyle can significantly reduce the risk of stomach cancer.
note that even with a high genetic risk and a healthy lifestyle of the above four points, the risk of stomach cancer was relatively reduced by 47% (HR=0.53 (0.29-0.99) and p=0.048).
in the genetically low, medium and high-risk groups, the 10-year absolute risk of stomach cancer, which adheres to a healthy lifestyle, was reduced by 0.82%, 0.94% and 1.12%, respectively.
The significance and limitation of the study on the effects of adhering to a healthy lifestyle on the risk of stomach cancer in different genetically loaded populations05 The results show that genetic risk and lifestyle together lead to the occurrence of stomach cancer, and the effects are independent and have a combined effect.
in populations with high genetic loads, adopting a healthy lifestyle can significantly reduce the incidence of stomach cancer, partially offsetting the genetic risk of stomach cancer.
results are of great significance to promote the identification and targeted development of gastric cancer prevention and secondary prevention in high-risk groups of gastric cancer in China.
published at the same time, Professor Massimo Rugge, from the University of Padua in Italy, argues that, in a sense, research design is even more intriguing than the results.
Statistical models take lifestyle factors into account for important results, that is, lifestyle significantly affects the risk of primary gastric cancer, providing an important contribution to the cognition of the multi-factor pathogenesis of stomach cancer, suggesting that the prevention strategy of primary gastric cancer can be adjusted according to the individual's exposure to environmental factors.
also innovatively assigned values to risk factor variables to facilitate understanding of the interaction between host genetics and participating in gastric carcinogenic cascading environmental factors," he said.
is reminiscent of what Galileo called 'measure what is measurable and make measurable what is not so', and in fact, the HRs proposed by the researchers changed the scene from empirical medicine to precision medicine.
" is worth noting that the study still has some limitations.
first, due to data acquisition limitations, the status of Helicobacter pyridobacteria infection was not included in the assessment, making it impossible to evaluate the effectiveness of multigene risk scores layered according to the status of Helicobacter pyridobacteria infection.
, lifestyle factors are self-reporting, which can lead to false stratation of lifestyle risk levels.
, lifestyle factors are assessed only at baselines, and changes in behavior during follow-up may affect risk stratage.
In fourth, the overall risk of stomach cancer is evaluated only, but genetic and lifestyle factors may vary depending on the tumor location (i.e., throttle or non-thyroid) or subtype (i.e., diffuse or intestinal), and details are not available in the CKB queue.
, the missing data of genotypes in different genotype arrays in the GWAS data set are interpolation, which may lead to some statistical bias.
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