NSAID Use, Folate Intake Linked to Lower Risk for Serrated Polyposis Syndrome

These study findings provide new evidence of the potentially protective role that folate, calcium and NSAIDs have against serrated polyposis syndrome.

Folate intake and nonsteroidal anti-inflammatory drug (NSAID) use are associated with a reduced risk for serrated polyposis syndrome (SPS), according to study results published in BMC Gastroenterology.

Researchers obtained case data from the Genetic Colonic Polyposis Study and included participants who met the World Health Organization (WHO) 2010 criteria I and/or III for SPS from 2007 and 2019 in Australia. Control participants were enrolled from the Australasian Colorectal Cancer Family Registry from 1996 to 2012.

Outcomes were SPS; SPS stratified by WHO criteria I, III and meeting both criteria; and SPS stratified by the presence or absence of colorectal cancer.

A total of 350 patients with SPS (median age, 39 years; 65% women) and 714 control individuals (median age, 50 years; 57% women) were included in the study. Among the patients with SPS, 150 (43%) fulfilled WHO criterion I, 67 (19%) fulfilled WHO criterion III, and 109 (31%) fulfilled both WHO criteria I and III for SPS. Of the group with SPS, 82 (23%) had colorectal cancer with the average age at colorectal cancer diagnosis being 53 years (IQR, 37-66).

Multivariate logistic analysis of risk factors for SPS showed an increased body mass index (BMI) at age 20 years was associated with SPS, with 9% (95% CI, 1.04-1.13; P <.001) increased odds of SPS for every 1 kg/cm2 increase in BMI at 20 years of age vs control participants. Taller participants had 7% increased odds of SPS, with 8% increased odds observed in a subgroup analysis of female participants. Increasing weekly intake of folate and NSAID use reduced the odds of SPS by 18% (95% CI, 0.75-0.90; P <.001) and 9% (95% CI, 0.86-0.97; P =.002), respectively.

This present study provided new evidence of the potentially protective role that folate, calcium, and NSAIDs use, low to moderate alcohol intake, and HRT may have on the development of SPS and on the development of CRC in SPS patients.

Hormone replacement therapy (HRT) was associated with 56% decreased odds of SPS (95% CI, 0.20-0.98; P =.043) compared with female participants who did not receive HRT.

Multivariate adjustment showed that female biological sex was associated with 2.14-fold (95% CI, 1.26-3.62; P =.005) increased odds of meeting WHO criterion I and 5.74-fold (95% CI, 2.72-12.10; P <.001) increased odds of fulfilling WHO I and III criteria vs male biological sex. Smoking more than 10 cigarettes per day was associated with reduced odds of fulfilling WHO criterion I by 0.16-fold (95% CI, 0.16; P =.001) and 0.45-fold (95% CI, 0.23-0.86; P =.015), respectively.

Calcium and folate intake were associated with decreased odds of fulfilling WHO criterion I by 21% (95% CI, 0.64-0.97; P =.021) and 16% (95% CI, 0.73-0.96; P =.010) for every extra dose taken per week, respectively. Weekly NSAIDs and folate intake were associated with reduced odds of achieving WHO criteria I and III by 12% (95% CI, 0.78-0.99; P =.028) and 18% (95% CI, 0.70-0.96; P =.012), respectively.

Separate multivariate models found that only age and NSAID use were associated with patients with colorectal cancer and SPS. Each extra weekly NSAID dose was associated with a 19% decrease in odds of colorectal cancer (95% CI, 0.67-0.98; P =.031) compared with control participants, and every 1-year increase in age increased the odds of colorectal cancer by 3% (95% CI, 1.00-1.07; P =.039) compared with control participants.

Patients with SPS and without colorectal cancer had an inverse association with elevated alcohol and wine intake. Those who consumed more than 350 g of alcohol per week had a 72% (95% CI, 0.09-0.94; P =.039) decrease in odds of SPS without colorectal cancer vs those who did not consume alcohol. Each increase in wine serving per week was associated with a decrease in odds of SPS without colorectal cancer by 5% (95% CI, 0.91-0.99; P =.016).

Limitations of the study include the fact that the exact dosage of medication and supplements in 1 tablet was not specified, family history of colorectal cancer and polyps was not assessed, and a low percentage of ACCFR control individuals had baseline colonoscopies.

The study authors conclude, “This present study provided new evidence of the potentially protective role that folate, calcium, and NSAIDs use, low to moderate alcohol intake, and HRT may have on the development of SPS and on the development of CRC in SPS patients.”

References:

Anthony E, Reece JC, Milanzi E, et al. Body mass index, sex, non-steroidal anti-inflammatory drug medications, smoking and alcohol are differentially associated with World Health Organisation criteria and colorectal cancer risk in people with serrated polyposis syndrome: an Australian case-control study. BMC Gastroenterol. 2022;22(1):489. doi:10.1186/s12876-022-02557-7