(P22-125-20) Gene-Environment Interactions Between PPARG2 Variant and Lifestyle Factors in Relation to Cancer RIsk: A Systematic Review

Objectives: A genetic variant in peroxisome proliferator-activated receptor-gamma (PPARG2 Pro12Ala; rs1801282) has been linked to both carcinogenesis and lifestyle factors such as energy balance and fat intake and identified as modifiers of risk in several different cancers. However, to date, no systematic review has been conducted. We conducted a systematic literature review to summarize the current evidence on whether associations between lifestyle factors and risk of cancer are modified by the PPARG2 Pro12Ala variant.

Methods: We conducted a systematic literature review of studies published before July 2019 using the PubMed database. We included observational studies that: 1) included diet, anthropometrics and physical activity as lifestyle factors; 2) had the risk of incident cancer in any site as an outcome; 3) included controls (participants free of cancer); and 4) reported a statistical significance of interaction effects between the PPARG2 variant and lifestyle factors.

Results: After applying the inclusion criteria to 3,424 identified abstracts, 14 studies of cancers in colon/rectum (n=6), breast (n=3), prostate (n=3), pancreas (n=1) and endometrium (n=1) were selected, which included a total of 22,267 participants with 9,290 cancer cases. Alcohol consumption had a statistically significant interaction with the PPARG2 variant in all three studies of colorectal and breast cancers investigating this interaction. Dietary factors such as fried food intake, refined grain intake, dietary vitamin A intake, lutein intake and Prudent dietary pattern significantly interacted with the PPARG2 variant, whereas other dietary factors such as dietary fat and meat intakes did not. Body mass index, waist-to-hip ratio and physical activity level did not significantly interact with the PPARG2 variant in all six studies of colorectal, breast, prostate, pancreatic and endometrial cancers, except for one study on body mass index and prostate cancer.

Conclusions: Our systematic review shows statistically significant, although inconsistent, interactions between PPARG2 Pro12Ala variant and lifestyle factors on cancer risk. This suggests that lifestyle recommendations for cancer prevention may need to be tailored based on genetic factors such as PPARG2 Pro12Ala variant.

Funding Sources: This study was funded by the OHSU/OSU Cancer Prevention and Control Initiative.