This study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late‐life cancer risk and explored the role of genetic and early‐life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30–50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case‐control data (controlled for the clustering of twins within a pair). A co‐twin matched case‐control analysis used conditional logistic regression to compare cancer‐discordant twins. Of all participants, 3,968 (26.9%) were overweight and 4,253 (28.8%) had cancer. In multi‐adjusted GEE models using normal‐weight (BMI 18.5–24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00‐1.84, P=0.049), liver cancer (OR 2.00, 95% CI: 1.11‐3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19‐6.91), and corpus uteri cancer (OR 1.78, 95% CI: 1.14‐2.78) but lower risk of non‐melanoma skin cancer (OR 0.77, 95% CI: 0.66‐0.90). In conditional logistic regression analysis, these associations were attenuated becoming non‐significance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late‐life colon, liver, and uterine cancer but reduced risk of late‐life non‐melanoma skin cancer. Further investigations are warranted to explore the role of genetic and early‐life environmental factors in these associations.
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