Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women

Abstract

Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK‐based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow‐up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types.

Abstract

What's new?

Evidence suggests that risk factors are differentially linked to colorectal cancer type and tumor site, suggesting that the disease can arise via distinct pathways, likely depending on the type of precancerous lesion. To explore risk factor associations by anatomical site and tumor morphology, the authors of this study examined data from the Million Women Study cohort, with more than 18,500 incident colorectal cancer cases. While there was little evidence for risk differences by tumor site, substantial differences were found for tumor morphology, particularly for smoking, which showed relative risks of twofold or more for some rare colorectal tumors.