GPX1 Pro198Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer

Rikke Dalgaard Hansen; Britta Naimi Krath; Kirsten Frederiksen; Anne Tjønneland; Kim Overvad; Nina Roswall; Steffen Loft; Lars Ove Dragsted; Ulla Birgitte Vogel; Ole Raaschou-Nielsen

doi:10.1016/j.mrfmmm.2009.01.009

GPX1 Pro¹⁹⁸Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer

Rikke Dalgaard Hansen, Britta Naimi Krath, Kirsten Frederiksen, Anne Tjønneland, Kim Overvad, Nina Roswall, Steffen Loft, Lars Ove Dragsted, Ulla Birgitte Vogel, Ole Raaschou-Nielsen

73 Citations (Scopus)

Abstract

GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro(198)Leu and OGG1 Ser(326)Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro(198)Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective "Diet, Cancer and Health" study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993-1997. GPX1 Pro(198)Leu, hOGG1 Ser(326)Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1(198)Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17-1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99-6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro(198)Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.

Original language	English
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	664
Issue number	1-2
Pages (from-to)	13-19
Number of pages	7
ISSN	0027-5107
DOIs	https://doi.org/10.1016/j.mrfmmm.2009.01.009
Publication status	Published - 2009

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Hansen, R. D., Krath, B. N., Frederiksen, K., Tjønneland, A., Overvad, K., Roswall, N., Loft, S., Dragsted, L. O., Vogel, U. B., & Raaschou-Nielsen, O. (2009). GPX1 Pro¹⁹⁸Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 664(1-2), 13-19. https://doi.org/10.1016/j.mrfmmm.2009.01.009

GPX1 Pro¹⁹⁸Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. / Hansen, Rikke Dalgaard; Krath, Britta Naimi; Frederiksen, Kirsten et al.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 664, No. 1-2, 2009, p. 13-19.

Research output: Contribution to journal › Journal article › Research › peer-review

Hansen, RD, Krath, BN, Frederiksen, K, Tjønneland, A, Overvad, K, Roswall, N, Loft, S , Dragsted, LO, Vogel, UB & Raaschou-Nielsen, O 2009, 'GPX1 Pro¹⁹⁸Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer', Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, vol. 664, no. 1-2, pp. 13-19. https://doi.org/10.1016/j.mrfmmm.2009.01.009

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title = "GPX1 Pro198Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer",

abstract = "GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro(198)Leu and OGG1 Ser(326)Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro(198)Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective {"}Diet, Cancer and Health{"} study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993-1997. GPX1 Pro(198)Leu, hOGG1 Ser(326)Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1(198)Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17-1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99-6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro(198)Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.",

author = "Hansen, {Rikke Dalgaard} and Krath, {Britta Naimi} and Kirsten Frederiksen and Anne Tj{\o}nneland and Kim Overvad and Nina Roswall and Steffen Loft and Dragsted, {Lars Ove} and Vogel, {Ulla Birgitte} and Ole Raaschou-Nielsen",

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T1 - GPX1 Pro198Leu polymorphism, erythrocyte GXP activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer

AU - Hansen, Rikke Dalgaard

AU - Krath, Britta Naimi

AU - Frederiksen, Kirsten

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Roswall, Nina

AU - Loft, Steffen

AU - Dragsted, Lars Ove

AU - Vogel, Ulla Birgitte

AU - Raaschou-Nielsen, Ole

PY - 2009

Y1 - 2009

N2 - GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro(198)Leu and OGG1 Ser(326)Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro(198)Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective "Diet, Cancer and Health" study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993-1997. GPX1 Pro(198)Leu, hOGG1 Ser(326)Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1(198)Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17-1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99-6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro(198)Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.

AB - GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro(198)Leu and OGG1 Ser(326)Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro(198)Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective "Diet, Cancer and Health" study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993-1997. GPX1 Pro(198)Leu, hOGG1 Ser(326)Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1(198)Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17-1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99-6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro(198)Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.

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DO - 10.1016/j.mrfmmm.2009.01.009

M3 - Journal article

SN - 0027-5107

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JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

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