Identification of novel modifiable risk factors of gastric adenocarcinoma

[摘要] Gastric cancer is the fifth most common occurred cancer worldwide. The predominant higher incidence of gastric cancer among males and the diminishing difference after age of 60 years suggests a potential protective effect of female hormones. In Chapter One, we found late age at natural menopause was associated with reduced risk of gastric cancer (≥55 vs. ≤ 45years old: HR=0.50, 95% CI: 0.25-0.99). Greater years of menstrual cycling were associated with a decreased risk of gastric adenocarcinoma (4th versus 1st quartile: HR=0.67, 95%CI: 0.46-0.96). Both ever use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were also associated with reduced risk of gastric adenocarcinoma; the HRs (95% CIs) were 0.40 (0.17-0.90) for use of HRT >3 years and 0.67 (0.47-0.94) for ever use of OCs, compared with never use. In Chapter Two, a prospective analysis of composite lifestyle factors and gastric cancer risk further elucidated that composite scores representing healthy lifestyles were significantly associated with reduced risk of gastric adenocarcinoma in a dose-dependent manner. HRs (95% CIs) for total, cardia, and non-cardia gastric adenocarcinoma for the highest (score 5) versus lowest composite score (score 0/1/2) were 0.42 (0.31-0.57), 0.22 (0.10-0.47), and 0.55 (0.39-0.78), respectively (all Ptrend<0.001). These findings are very encouraging for a comprehensive strategy for promoting healthy living that could be effective for primary prevention of gastric cancer even in populations with a relatively high background risk of gastric cancer and high prevalence of H. pylori. No prospective evidence was available to elucidate the association between extreme telomere length and gastric cancer risk. In Chapter Three, we conducted a prospective analysis found that both extreme short (1st vs. 2nd quintile: HR=1.63, 95% CI: 1.08-2.47) and long (5th vs. 2nd quintile: HR=1.55, 95% CI: 0.97-2.47) telomere length is associated with increased risk of gastric adenocarcinoma. The public health significance of these findings is the identification of novel modifiable risk factors among certain population subgroups with high risk of gastric adenocarcinoma and paving way for future preventative strategies.

[发布机构] the University of Pittsburgh