Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Abstract

BackgroundPatients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.Methods and FindingsWe identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.ConclusionA decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

Hyperplastic polyp of the duodenum: a report of 9 cases with immunohistochemical and molecular findings

“…Although small numbers of HPs measuring at most 5 mm are a common finding in the distal colorectum after 50 years of age, the occurrence of multiple serrated polyps at an earlier age throughout the colon may be associated with serrated polyposis, also known as hyperplastic polyposis syndrome [12]. Patients with this syndrome are at increased risk for the development of colorectal cancer, up to 40% [26,27].…”

“…V600E BRAF mutation analysis was performed by a fluorescent allele-specific PCR assay, as previously described [12]. The mutant allele primer generated a PCR product of 97 base pairs, 3 base pairs larger than the wild-type PCR product after separation on an ABI 3100 genetic analyzer (Applied Biosystems, Mulgrave, VIC, Australia).…”

KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis

“…The somatic TNA mutation at nucleotide 1799 causing the V600E mutation in the BRAF gene was determined using a fluorescent allele-specific PCR assay as has been previously described [25]. Briefly, 20 to 50 ng of DNA, extracted from formalin-fixed, paraffin-embedded tumor tissue, was amplified in a 25-μL reaction containing 100 nmol/L each of allele-specific primers tagged with differing fluorophores (mutant primer [F1]: 6-Fam-5′-CAGTGATTTTGGTCTAGCTTCAGA-3′; wild-type primer (F2): NED-5′-TGATTTTGGTCTAGCTACAGT-3′; and a common reverse primer [reverse primer, REV]: 5′-CTC-AATTCTTACCATCCACAAAATG-3′), together with 2.5 units of Taq polymerase (Eppendorf, Hamburg, Germany), 1× buffer and 200 μmol/L of deoxyribonucleotide triphosphatase (dNTP).…”

Yield of Screening Colonoscopy in First-degree Relatives of Patients With Serrated Polyposis Syndrome

“…[1][2][3] SPS is a relatively common finding in patients undergoing fecal immunochemical testing (FIT)-based colorectal cancer screening, with an estimated prevalence of 1:150 to 300. 4,5 In an average-risk screening population the prevalence is estimated to be 1:1800, which is more frequent in occurrence than for instance familial adenomatous polyposis (1:13,000).…”