Abstract
There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23–3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11–1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.
Highlights
Subjects who met the Amsterdam/Bethesda criteria for Lynch Syndrome (LS) [16]; colorectal cancer (CRC) risk was evaluated as study endpoint [17]; (ii) the manuscript includes risk estimates and 95% confidence interval (CI) for BMI/weight status assessment; (iii) the studies have to be independent; the study design is a cohort study or a case-control study
Pathogenic variants in each of the mismatch repair (MMR) genes result in different cancer risks for different organs, mainly colorectum and endometrium, and including ovaries, stomach, small bowel, bile ducts, pancreas, and upper urinary tract
We found that obesity was associated with a significantly increased risk of CRC in men, but not in women
Summary
Colorectal cancer (CRC) accounts for approximately 10% of all annually diagnosed cancers and cancer-related deaths worldwide [1]. Of all new cases of CRC, 3% are attributable to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome (LS) [2]. LS runs in families in an autosomal dominant inheritance pattern and is the most common cause of hereditary colorectal cancer [3]. The diagnosis is made upon identification of a germline mutation in a mismatch repair (MMR) gene (MLH1, MSH2, MSH6, or PMS2)
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