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.
Highlights
Familial non-syndromic colorectal cancer (CRC) constitutes one of the most difficult and diverse patient groups encountered in a genetics clinic, with no apparent germline mutation, an oftenindeterminant mode of inheritance, and questions arising as to how to manage the probands, and how to identify which family members are at risk for CRC
A 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
The frequency of patients from Australasia presenting with CRC (37%) was not different significantly from that of North America (42%) (P = 0.8)
Summary
Familial non-syndromic colorectal cancer (CRC) constitutes one of the most difficult and diverse patient groups encountered in a genetics clinic, with no apparent germline mutation, an oftenindeterminant mode of inheritance, and questions arising as to how to manage the probands, and how to identify which family members are at risk for CRC One such condition is hyperplastic polyposis syndrome (HPS), a colorectal polyposis of unknown etiology characterized by the development of multiple serrated polyps in the large intestine. An alternative phenotype of HPS demonstrates fewer polyps than that described above includes a diversity of polyp types including common hyperplastic polyps, serrated adenomas, sessile serrated adenomas, traditional adenomas, and polyps with mixed elements [1,11] This second phenotype of HPS is reported to be more likely to have polyps with diameters exceeding 1cm, dysplastic changes, to involve the proximal colon and to be associated with the presence of CRC [6]. The aim of this work was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps
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