Diet, lifestyle, heritable factors and colorectal carcinogenesis: associations with histopathological and molecular endpoints
Background: Diet, lifestyle and heritable factors have been related to colorectal cancer risk; to date, their relevance to the overall scope of colorectal carcinogenesis, has not been clearly established.Aim and Methods: To evaluate whether distinguishing colorectal tissue by its histopathological and molecular characteristics sheds further light on the etiology of colorectal cancer. Five research questions addressed associations between diet, lifestyle and heritable factors, and specific tissue characteristics.Results: First, we observed that consumption of fruits, in particular citrus fruits, was associated with increased rectal glutathione S-transferase activity in a cross-sectional study of 94 Dutch individuals. Consumption of cruciferous vegetables was also associated with increased activity, but only among individuals who carried the GSTM1 genotype.Second, we observed that intake of vitamin B2 was inversely associated with adenomas with a K-ras mutation (n=81) but not with adenomas without a K-ras mutation (n=453) in a case-control study conducted in the Netherlands. A positive association with monounsaturated fat was confined to K-ras mutation-negative adenomas. We found indications for differential associations with some additional factors, but the epidemiological evidence on risk factors and K-ras mutations remains inconsistent.Third, in a cohort study of 26,769 American men, we observed that most risk factors were similarly associated with advanced (=1cm or with any villous characteristics or carcinoma in situ) and non-advanced colorectal adenomas after 17 years of follow-up. However, smoking had a stronger positive association with advanced adenomas than with non-advanced adenomas, and ahigh glycemic index was inversely associated with advanced but not with non-advanced adenomas.Fourth, associations with family history of colorectal cancer were stronger for men with multiple distal adenomas than for men with a single distal adenoma at first diagnosis, in the aforementioned cohort study among US men. Associations between family history, and advanced and non-advanced adenomas, were of similar strength, but a tendency towards a somewhat stronger association with non-advanced adenomas was found.Fifth, fruit consumption was inversely associated with hMLH1 protein-deficient colon cancer (n=54) but not with hMLH1 protein-proficient colon cancer (n=387) in a cohort study of 120,852 people who were followed-up over 7.3 years, while ignoring information from the initial 2.3 years of follow-up. Clear associations with consumption of vegetables, or nutrients related to fruits and vegetables, could not be detected.Conclusions: We showed that distinguishing colorectal tumors by their histopathological and molecular characteristics may indeed shed further light on the role of diet, lifestyle and heritable factors in colorectal carcinogenesis. Such an approach may alleviate some of the weaknesses of traditional epidemiology, but also adds another layer of complexity. It is a challenge for the future to develop a framework into which specific associations can be integrated, using risk markers signaling the molecular and biochemical pathways from normal to cancerous tissue.
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| Format: | Doctoral thesis biblioteca |
| Language: | English |
| Subjects: | carcinogenesis, colorectal cancer, diet, fruit, histopathology, inheritance, lifestyle, vegetables, carcinogenese, colorectaal kanker, dieet, groenten, histopathologie, levensstijl, overerving, |
| Online Access: | https://research.wur.nl/en/publications/diet-lifestyle-heritable-factors-and-colorectal-carcinogenesis-as |
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| Summary: | Background: Diet, lifestyle and heritable factors have been related to colorectal cancer risk; to date, their relevance to the overall scope of colorectal carcinogenesis, has not been clearly established.Aim and Methods: To evaluate whether distinguishing colorectal tissue by its histopathological and molecular characteristics sheds further light on the etiology of colorectal cancer. Five research questions addressed associations between diet, lifestyle and heritable factors, and specific tissue characteristics.Results: First, we observed that consumption of fruits, in particular citrus fruits, was associated with increased rectal glutathione S-transferase activity in a cross-sectional study of 94 Dutch individuals. Consumption of cruciferous vegetables was also associated with increased activity, but only among individuals who carried the GSTM1 genotype.Second, we observed that intake of vitamin B2 was inversely associated with adenomas with a K-ras mutation (n=81) but not with adenomas without a K-ras mutation (n=453) in a case-control study conducted in the Netherlands. A positive association with monounsaturated fat was confined to K-ras mutation-negative adenomas. We found indications for differential associations with some additional factors, but the epidemiological evidence on risk factors and K-ras mutations remains inconsistent.Third, in a cohort study of 26,769 American men, we observed that most risk factors were similarly associated with advanced (=1cm or with any villous characteristics or carcinoma in situ) and non-advanced colorectal adenomas after 17 years of follow-up. However, smoking had a stronger positive association with advanced adenomas than with non-advanced adenomas, and ahigh glycemic index was inversely associated with advanced but not with non-advanced adenomas.Fourth, associations with family history of colorectal cancer were stronger for men with multiple distal adenomas than for men with a single distal adenoma at first diagnosis, in the aforementioned cohort study among US men. Associations between family history, and advanced and non-advanced adenomas, were of similar strength, but a tendency towards a somewhat stronger association with non-advanced adenomas was found.Fifth, fruit consumption was inversely associated with hMLH1 protein-deficient colon cancer (n=54) but not with hMLH1 protein-proficient colon cancer (n=387) in a cohort study of 120,852 people who were followed-up over 7.3 years, while ignoring information from the initial 2.3 years of follow-up. Clear associations with consumption of vegetables, or nutrients related to fruits and vegetables, could not be detected.Conclusions: We showed that distinguishing colorectal tumors by their histopathological and molecular characteristics may indeed shed further light on the role of diet, lifestyle and heritable factors in colorectal carcinogenesis. Such an approach may alleviate some of the weaknesses of traditional epidemiology, but also adds another layer of complexity. It is a challenge for the future to develop a framework into which specific associations can be integrated, using risk markers signaling the molecular and biochemical pathways from normal to cancerous tissue. |
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