Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism

Jabłońska, Ewa; Gromadzińska, Jolanta; Sobala, Wojciech; Reszka, Edyta; Wąsowicz, Wojciech

doi:10.1007/s00394-008-0696-9

Cited by 96 publications

(61 citation statements)

References 30 publications

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“…Rs5845 and rs5859 are SNPs in a region of the SEP15 gene corresponding to the 3 0 UTR; they are closely linked, and their modulation of the ability of the 3 0 UTR to promote reporter gene activity [13] indicates that they have functional consequences. Furthermore, the SNPs have been reported to affect breast cancer risk [13] and risk of lung cancer in smokers [14]. The present results indicate that the SNPs influence rectal cancer risk in men.…”

Section: Discussionsupporting

confidence: 65%

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

et al. 2010

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Selenium (Se), a dietary trace metal essential for human health, is incorporated into *25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.

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Section: Discussionsupporting

confidence: 65%

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

et al. 2010

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“…Another meta-analysis of epidemiological data concluded that despite evidence for an inverse association between Se exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases (79). One of these factors is genetic background-a study among smokers demonstrated that depending on a 15-kDa selenoprotein genetic polymorphism, smoking individuals either can benefit from a higher Se intake or have an increased risk for lung cancer (161). Together, the results from a number of ongoing randomized controlled trials (79,119) should help to better understand the general effect of selenium in cancer.…”

Section: E Seleniummentioning

confidence: 99%

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

Samoylenko

Hossain²,

Mennerich³

et al. 2013

Antioxidants & Redox Signaling

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Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent largescale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials.

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“…4 Sep15 polymorphism is associated with lung cancer. 283 GPx2 is upregulated in some types of cancer, particularly of gastrointestinal origin. 284 A recent study has shown that lower expression of GPx2 increases migration and invasion of cancer cell clones, but decreases their growth, thus depending on the stage of tumour development.…”

Section: Male Infertilitymentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

631

451

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism

Abstract: It appears that among smoking individuals, those with the Sep15 1125 AA genotype may benefit most from a higher Se intake, whereas in those with the GG or GA genotype, a higher Se status may increase the risk for lung cancer.

Cited by 96 publications

References 30 publications

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

Selenium biochemistry and its role for human health

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