Weight change in adults tied to colorectal adenoma risk

Weight loss during adulthood, particularly among overweight or obese individuals, is associated with a reduction in the risk of developing distal colorectal adenomas – a precursor to colorectal cancer, whereas weight gain increased its risk, according to findings from the PLCO* Cancer Screening Trial.

“Although obesity is a known risk factor [for colorectal carcinogenesis], the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention,” said the researchers. “[As such,] we prospectively assessed the associations between weight change, including both weight loss and gain, over different periods of adulthood and risk of incident colorectal adenoma.”

Using self-reported weight data, the team evaluated weight change in participants (n=1,053/16,576 [cases/controls**]; mean age 62 years) during early-late (from age 20 years to baseline***), early-middle (20–50 years), and middle-late (from age 50 years to baseline) adulthood. [JNCI Cancer Spectr 2022;6:pkab098]

 

Weight loss = reduced risk

Compared with stable weight^#, weight loss^# during early-late adulthood was associated with a reduction in adenoma risk (odds ratio [OR], 0.54). Results were similar for weight loss during early-middle adulthood (OR, 0.57) but less pronounced for middle-late adulthood (OR, 0.85).

“[This] may be in part because weight loss at younger ages is more likely to be intentional (eg, diet and/or exercise). In contrast, weight loss at older ages may be more likely unintentional (eg, illness),” the researchers explained.

When stratifying by starting BMI (ie, BMI at age 20 or 50 years), the effect was more pronounced among those who were overweight or obese (OR, 0.39), but not for those who had a starting BMI of <25 kg/m² at age 20 years (OR, 0.79).

 

Weight gain = increased risk

Conversely, weight gain^# during early-late adulthood was tied to increased adenoma risk, with the risk being greater among participants in the highest gain group (ie, >3 kg/5 years) vs those with stable weight (OR, 1.30; p_trend<0.001). There were also positive associations for weight gain during early-middle (OR, 1.08; p_trend=0.06) and middle-late adulthood (OR, 1.18; p_trend=0.002).

According to the researchers, these findings could not have been due to starting BMI as all models were adjusted for starting BMI. “[The] positive associations [across] all three time periods [suggests] the importance of weight gain throughout adulthood in adenoma risk.” The increased signalling of insulin-like growth factor 1 due to insulin resistance and consequent hyperinsulinaemia may promote colorectal neoplasia via reduced apoptosis and increased cell proliferation. [Recent Results Cancer Res 2016;208:17-41]

 

Men vs women

Stratification by sex showed more pronounced effects in men vs women, both in terms of the associations between weight loss and adenoma risk reduction (ORs, 0.50 vs 0.65) and between weight gain and increased adenoma risk during early-late adulthood (ORs for >3 kg/5 years, 1.41 vs 1.09).

The differences by sex may have been driven by the greater amount of visceral and hepatic adipose tissues in men than women despite having the same BMI. [Gend Med 2009;6:60-75] “Another possible mechanism could be due to the modifying effect of oestrogen, [owing to evidence showing] that obesity is positively associated with oestrogen production in women, and oestrogens have a protective effect against colorectal carcinogenesis,” said the researchers.

 

Maintain a healthy weight

Studies evaluating the link between colorectal adenoma risk and obesity mostly target only one timepoint, and most focus on weight gain. [Am J Gastroenterol 2012;107:1175-1185] “Although additional studies are needed to replicate these findings, our study highlights the importance of healthy weight maintenance and avoidance of weight gain throughout adulthood in preventing colorectal adenoma,” said the researchers.

“Given the rise in obesity among adults, our findings suggest weight loss may help prevent adenoma in addition to other known health benefits,” they added.