Scholarlink

Introduction <p><i>Helicobacter pylori</i> (HP) is a well-established gastric carcinogen. But it shows inconsistent association with colorectal cancer (CRC) across diverse study populations.</p> Methods <p>We investigated participants from the UK biobank. HP-seropositive cases and peptic ulcer diseases (PUDs) were identified. The primary outcome was CRC. We estimated the cumulative incidence using a competing risk model measured by the hazard ratios (HRs) with 95% confidence intervals (CIs) with adjustment. We did a genome-wide interaction analysis to identify genetic variants that modify HP-serology-CRC associations with exploratory gene-based and gene-set analysis. We further did a bidirectional two-sample Mendelian randomization (MR) to investigate the causal relation of gene-proxied PUD on CRC of the European ancestry and of the East Asian ancestry.</p> Results <p>We included 492,490 participants with a median follow-up of 14.7 years. HP sero-positivity did not significantly increase the incidence of CRC (adjusted HR = 0.76, 95% CI 0.53 − 1.10, <i>p</i> = 0.15). No SNP was identified to be significantly interacted with HP serology to modify CRC risk. The risk of CRC for PUD cases was not significantly different from non-PUD cases after adjusting (adjusted HR = 0.88, 95% CI 0.76 − 1.02, <i>p</i> = 0.09). The gene-proxied PUD causally increased the incidence of colon cancer of the East Asian ancestry (OR = 1.47, 95% CI = 1.00 − 2.15, <i>p</i> = 0.047), not of the European ancestry (OR = 1.03, 95% CI = 0.79 − 1.34, <i>p</i> = 0.82).</p> Conclusions <p>Neither seropositivity for HP nor PUD showed a robust increase on the risk of CRC in a 15-year follow-up. The causal relation of PUD on CRC was significant of East Asian ancestry, not of European ancestry.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Helicobacter pylori, peptic ulcer disease, and colorectal cancer: a prospective study with genome-wide interaction analysis and Mendelian randomization

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月29日

查看全文
  • Ziqi Wan,
  • Jiarui Mi,
  • Xiaoyin Bai,
  • Dong Wu,
  • Sunny Hei Wong

摘要

Introduction

Helicobacter pylori (HP) is a well-established gastric carcinogen. But it shows inconsistent association with colorectal cancer (CRC) across diverse study populations.

Methods

We investigated participants from the UK biobank. HP-seropositive cases and peptic ulcer diseases (PUDs) were identified. The primary outcome was CRC. We estimated the cumulative incidence using a competing risk model measured by the hazard ratios (HRs) with 95% confidence intervals (CIs) with adjustment. We did a genome-wide interaction analysis to identify genetic variants that modify HP-serology-CRC associations with exploratory gene-based and gene-set analysis. We further did a bidirectional two-sample Mendelian randomization (MR) to investigate the causal relation of gene-proxied PUD on CRC of the European ancestry and of the East Asian ancestry.

Results

We included 492,490 participants with a median follow-up of 14.7 years. HP sero-positivity did not significantly increase the incidence of CRC (adjusted HR = 0.76, 95% CI 0.53 − 1.10, p = 0.15). No SNP was identified to be significantly interacted with HP serology to modify CRC risk. The risk of CRC for PUD cases was not significantly different from non-PUD cases after adjusting (adjusted HR = 0.88, 95% CI 0.76 − 1.02, p = 0.09). The gene-proxied PUD causally increased the incidence of colon cancer of the East Asian ancestry (OR = 1.47, 95% CI = 1.00 − 2.15, p = 0.047), not of the European ancestry (OR = 1.03, 95% CI = 0.79 − 1.34, p = 0.82).

Conclusions

Neither seropositivity for HP nor PUD showed a robust increase on the risk of CRC in a 15-year follow-up. The causal relation of PUD on CRC was significant of East Asian ancestry, not of European ancestry.