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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Research about marijuana and fertility is limited but some previous studies suggested that it might harm semen quality. Smoking of any type is also known to be a risk factor for male infertility. So, men who have smoked cannabis are expected to have worse measures of fertility but the data from a recent study suggested the opposite. The finding contradicts all conventional knowledge on how weed affects sperm. This may be because previous research typically focused on men with drug abuse history but this present study simply asked men if they had smoked more than two joints in their life.

 

Analysis of 1,143 semen samples from 662 men collected between 2000 and 2017 at the Fertility Clinic at Massachusetts General Hospital showed that those who had smoked weed at some point in their life had a mean sperm concentration of 62.7 million sperm per milliliter (mL) of ejaculate, while men who avoided marijuana entirely had mean concentrations of 45.4 million/mL. Added to this only 5% of weed smokers had sperm concentrations below the 15 million/mL threshold the World Health Organization has set for a “normal” sperm count, versus 12% of men who never smoked marijuana.

 

The study has some imperfections such as the participants are not necessarily representative of the general population. They were predominantly college educated men with a mean age of 36, and were all seeking treatment at a fertility center. Further research is needed to support the findings. Two possibilities are put forward by the researchers as the reason behind such data. The first is that low levels of marijuana could have a positive effect on the endocannabinoid system, the neurotransmitters in the nervous system that bind to cannabinoid receptors, and are known to regulate fertility. The second is that may be weed-smokers are just bigger risk takers and men with higher testosterone levels and thus have better sperm count.

 

But, there’s certainly no medical recommendation to smoke weed as a fertility treatment but this study, at least, suggests that a little marijuana doesn’t hurt and might benefit sperm production in some way. But, the researchers specified that their finding does not necessarily mean that smoking cannabis increases the chances of fatherhood.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/30726923

 

https://www.bloomberg.com/amp/news/articles/2019-02-06/cannabis-smoking-associated-with-higher-sperm-count-study-finds?__twitter_impression=true

 

https://qz.com/1543564/smoking-weed-linked-to-higher-sperm-count-in-a-harvard-study/

 

https://www.thestar.com.my/news/world/2019/02/06/cannabis-smoking-associated-with-higher-sperm-count-study-finds/

 

http://time.com/5520421/smoking-marijuana-sperm-fertility/

 

https://www.health.com/infertility/marijuana-sperm-count

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Unexpected Genetic Vulnerability to Menthol Cigarette Use

Reporter: Irina Robu, PhD

According to a study published in PLOS genetics, a group of international researchers supported by U.S. Food and Drug Administration and the National Institute of Health have found a genetic variant of MRGPRX4 gene in people of African descent that increases a smoker’s preference for cigarettes containing menthol. The FDA determined that

  • nearly 20 million people of African American origin in the United States smoke menthol cigarette.
  • Research has shown that 86 percent of African-American smokers use menthol cigarettes in comparison to the smokers of European descent which are less than 30 percent.

In this study, the researcher Andrew Griffith uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes. The results can help public health agencies to develop strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable.

At the same time, researchers at University of Texas Southwestern Medical Center led by Dennis Drayna, conducted a detail genetic analyses on 13000 adults using data from a multiethnic, population-based group of smokers from the Dallas Heart Study and from an African-American group of smokers from the Dallas Biobank.

The researchers report that

  • 5 to 8 percent of the African-American study participants had the gene variant.
  • None of the participants of European, Asian, or Native American descent had the variant.
  • Recognizing the genetic variant, pointed the researchers in an unanticipated direction, leading them to offer
  • the first characterization of this naturally-occurring MRGPRX4 variant in humans.
  • The gene codes for a sensor/receptor is believed to be involved in detecting and responding to irritants from the environment in the lungs and airways.

Drayna further stated that while the gene variant can’t explain all of the increased use of menthol cigarettes by African-Americans, the results show that this variant is a theoretically vital factor that motivates the predilection for menthol cigarettes in the population.

Source

https://www.nih.gov/news-events/news-releases/researchers-find-genetic-vulnerability-menthol-cigarette-use

 

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Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

Curator, Writer: Stephen J. Williams, Ph.D.

lung cancer

(photo credit: cancer.gov)

A report Lung Cancer Genome Surveys Find Many Potential Drug Targets, in the NCI Bulletin,

http://www.cancer.gov/ncicancerbulletin/091812/page2

summarizes the clinical importance of five new lung cancer genome sequencing projects. These studies have identified genetic and epigenetic alterations in hundreds of lung tumors, of which some alterations could be taken advantage of using currently approved medications.

The reports, all published this month, included genomic information on more than 400 lung tumors. In addition to confirming genetic alterations previously tied to lung cancer, the studies identified other changes that may play a role in the disease.

Collectively, the studies covered the main forms of the disease—lung adenocarcinomas, squamous cell cancers of the lung, and small cell lung cancers.

“All of these studies say that lung cancers are genomically complex and genomically diverse,” said Dr. Matthew Meyerson of Harvard Medical School and the Dana-Farber Cancer Institute, who co-led several of the studies, including a large-scale analysis of squamous cell lung cancer by The Cancer Genome Atlas (TCGA) Research Network.

Some genes, Dr. Meyerson noted, were inactivated through different mechanisms in different tumors. He cautioned that little is known about alterations in DNA sequences that do not encode genes, which is most of the human genome.

Four of the papers are summarized below, with the first described in detail, as the Nature paper used a multi-‘omics strategy to evaluate expression, mutation, and signaling pathway activation in a large cohort of lung tumors. A literature informatics analysis is given for one of the papers.  Please note that links on GENE names usually refer to the GeneCard entry.

Paper 1. Comprehensive genomic characterization of squamous cell lung cancers[1]

The Cancer Genome Atlas Research Network Project just reported, in the journal Nature, the results of their comprehensive profiling of 230 resected lung adenocarcinomas. The multi-center teams employed analyses of

  • microRNA
  • Whole Exome Sequencing including
    • Exome mutation analysis
    • Gene copy number
    • Splicing alteration
  • Methylation
  • Proteomic analysis

Summary:

Some very interesting overall findings came out of this analysis including:

  • High rates of somatic mutations including activating mutations in common oncogenes
  • Newly described loss of function MGA mutations
  • Sex differences in EGFR and RBM10 mutations
  • driver roles for NF1, MET, ERBB2 and RITI identified in certain tumors
  • differential mutational pattern based on smoking history
  • splicing alterations driven by somatic genomic changes
  • MAPK and PI3K pathway activation identified by proteomics not explained by mutational analysis = UNEXPLAINED MECHANISM of PATHWAY ACTIVATION

however, given the plethora of data, and in light of a similar study results recently released, there appears to be a great need for additional mining of this CGAP dataset. Therefore I attempted to curate some of the findings along with some other recent news relevant to the surprising findings with relation to biomarker analysis.

Makeup of tumor samples

230 lung adenocarcinomas specimens were categorized by:

Subtype

33% acinar

25% solid

14% micro-papillary

9% papillary

8% unclassified

5% lepidic

4% invasive mucinous
Gender

Smoking status

81% of patients reported past of present smoking

The authors note that TCGA samples were combined with previous data for analysis purpose.

A detailed description of Methodology and the location of deposited data are given at the following addresses:

Publication TCGA Web Page: https://tcga-data.nci.nih.gov/docs/publications/luad_2014/

Sequence files: https://cghub.ucsc.edu

Results:

Gender and Smoking Habits Show different mutational patterns

 

WES mutational analysis

  1. a) smoking status

– there was a strong correlations of cytosine to adenine nucleotide transversions with past or present smoking. In fact smoking history separated into transversion high (past and previous smokers) and transversion low (never smokers) groups, corroborating previous results.

mutations in groups              Transversion High                   Transversion Low

TP53, KRAS, STK11,                 EGFR, RB1, PI3CA

     KEAP1, SMARCA4 RBM10

 

  1. b) Gender

Although gender differences in mutational profiles have been reported, the study found minimal number of significantly mutated genes correlated with gender. Notably:

  • EGFR mutations enriched in female cohort
  • RBM10 loss of function mutations enriched in male cohort

Although the study did not analyze the gender differences with smoking patterns, it was noted that RBM10 mutations among males were more prevalent in the transversion high group.

Whole exome Sequencing and copy number analysis reveal Unique, Candidate Driver Genes

Whole exome sequencing revealed that 62% of tumors contained mutations (either point or indel) in known cancer driver genes such as:

KRAS, EGFR, BRMF, ERBB2

However, authors looked at the WES data from the oncogene-negative tumors and found unique mutations not seen in the tumors containing canonical oncogenic mutations.

Unique potential driver mutations were found in

TP53, KEAP1, NF1, and RIT1

The genomics and expression data were backed up by a proteomics analysis of three pathways:

  1. MAPK pathway
  2. mTOR
  3. PI3K pathway

…. showing significant activation of all three pathways HOWEVER the analysis suggested that activation of signaling pathways COULD NOT be deduced from DNA sequencing alone. Phospho-proteomic analysis was required to determine the full extent of pathway modification.

For example, many tumors lacked an obvious mutation which could explain mTOR or MAPK activation.

 

Altered cell signaling pathways included:

  • Increased MAPK signaling due to activating KRAS
  • Higher mTOR due to inactivating STK11 leading to increased proliferation, translation

Pathway analysis of mutations revealed alterations in multiple cellular pathways including:

  • Reduced oxidative stress response
  • Nucleosome remodeling
  • RNA splicing
  • Cell cycle progression
  • Histone methylation

Summary:

Authors noted some interesting conclusions including:

  1. MET and ERBB2 amplification and mutations in NF1 and RIT1 may be unique driver events in lung adenocarcinoma
  2. Possible new drug development could be targeted to the RTK/RAS/RAF pathway
  3. MYC pathway as another important target
  4. Cluster analysis using multimodal omics approach identifies tumors based on single-gene driver events while other tumor have multiple driver mutational events (TUMOR HETEROGENEITY)

Paper 2. A Genomics-Based Classification of Human Lung Tumors[2]

The paper can be found at

http://stm.sciencemag.org/content/5/209/209ra153

by The Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM),*,

Paper Summary

This sequencing project revealed discrepancies between histologic and genomic classification of lung tumors.

Methodology

– mutational analysis by whole exome sequencing of 1255 lung tumors of histologically

defined subtypes

– immunohistochemistry performed to verify reclassification of subtypes based on sequencing data

Results

  • 55% of all cases had at least one oncogenic alteration amenable to current personalized treatment approaches
  • Marked differences existed between cluster analysis within and between preclassified histo-subtypes
  • Reassignment based on genomic data eliminated large cell carcinomas
  • Prospective classification of 5145 lung cancers allowed for genomic classification in 75% of patients
  • Identification of EGFR and ALK mutations led to improved outcomes

Conclusions:

It is feasible to successfully classify and diagnose lung tumors based on whole exome sequencing data.

Paper 3. Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers[3]

A link to the paper can be found here with Graphic Summary: http://www.cell.com/cell/abstract/S0092-8674%2812%2901022-7?cc=y?cc=y

Methodology

  • Whole genome sequencing and transcriptome sequencing of cancerous and adjacent normal tissues from 17 patients with NSCLC
  • Integrated RNASeq with WES for analysis of
    • Variant analysis
    • Clonality by variant allele frequency anlaysis
    • Fusion genes
  • Bioinformatic analysis

Results

  • 3,726 point mutations and more than 90 indels in the coding sequence
  • Smokers with lung cancer show 10× the number of point mutations than never-smokers
  • Novel lung cancer genes, including DACH1, CFTR, RELN, ABCB5, and HGF were identified
  • Tumor samples from males showed high frequency of MYCBP2 MYCBP2 involved in transcriptional regulation of MYC.
  • Variant allele frequency analysis revealed 10/17 tumors were at least biclonal while 7/17 tumors were monoclonal revealing majority of tumors displayed tumor heterogeneity
  • Novel pathway alterations in lung cancer include cell-cycle and JAK-STAT pathways
  • 14 fusion proteins found, including ROS1-ALK fusion. ROS1-ALK fusions have been frequently found in lung cancer and is indicative of poor prognosis[4].
  • Novel metabolic enzyme fusions
  • Alterations were identified in 54 genes for which targeted drugs are available.           Drug-gable mutant targets include: AURKC, BRAF, HGF, EGFR, ERBB4, FGFR1, MET, JAK2, JAK3, HDAC2, HDAC6, HDAC9, BIRC6, ITGB1, ITGB3, MMP2, PRKCB, PIK3CG, TERT, KRAS, MMP14

Table. Validated Gene-Fusions Obtained from Ref-Seq Data

Note: Gene columns contain links for GeneCard while Gene function links are to the    gene’s GO (Gene Ontology) function.

GeneA (5′) GeneB (3′) GeneA function (link to Gene Ontology) GeneB function (link to Gene Ontology) known function (refs)
GRIP1 TNIP1 glutamate receptor IP transcriptional repressor
SGMS1 STK10 sphingolipid synthesis ser/thr kinase
RASSF3 TTYH2 GTP-binding protein chloride anion channel
KDELR2 ROS1, GOPC ER retention seq. binding proto-oncogenic tyr kinase
ACSL4 DCAF6 fatty acid synthesis ?
MARCH8 PRKG1 ubiquitin ligase cGMP dependent protein kinase
APAF1 UNC13B, TLN1 caspase activation cytoskeletal
EML4 ALK microtubule protein tyrosine kinase
EDR3,PHC3 LOC441601 polycomb pr/DNA binding ?
DKFZp761L1918,RHPN2 ANKRD27 Rhophilin (GTP binding pr ankyrin like
VANGL1 HAO2 tetraspanin family oxidase
CACNA2D3 FLNB VOC Ca++ channel filamin (actin binding)

Author’s Note:

There has been a recent literature on the importance of the EML4-ALK fusion protein in lung cancer. EML4-ALK positive lung tumors were found to be les chemo sensitive to cytotoxic therapy[5] and these tumor cells may exhibit an epitope rendering these tumors amenable to immunotherapy[6]. In addition, inhibition of the PI3K pathway has sensitized EMl4-ALK fusion positive tumors to ALK-targeted therapy[7]. EML4-ALK fusion positive tumors show dependence on the HSP90 chaperone, suggesting this cohort of patients might benefit from the new HSP90 inhibitors recently being developed[8].

Table. Significantly mutated genes (point mutations, insertions/deletions) with associated function.

Gene Function
TP53 tumor suppressor
KRAS oncogene
ZFHX4 zinc finger DNA binding
DACH1 transcription factor
EGFR epidermal growth factor receptor
EPHA3 receptor tyrosine kinase
ENSG00000205044
RELN cell matrix protein
ABCB5 ABC Drug Transporter

Table. Literature Analysis of pathways containing significantly altered genes in NSCLC reveal putative targets and risk factors, linkage between other tumor types, and research areas for further investigation.

Note: Significantly mutated genes, obtained from WES, were subjected to pathway analysis (KEGG Pathway Analysis) in order to see which pathways contained signicantly altered gene networks. This pathway term was then used for PubMed literature search together with terms “lung cancer”, “gene”, and “NOT review” to determine frequency of literature coverage for each pathway in lung cancer. Links are to the PubMEd search results.

KEGG pathway Name # of PUBMed entries containing Pathway Name, Gene ANDLung Cancer
Cell cycle 1237
Cell adhesion molecules (CAMs) 372
Glioma 294
Melanoma 219
Colorectal cancer 207
Calcium signaling pathway 175
Prostate cancer 166
MAPK signaling pathway 162
Pancreatic cancer 88
Bladder cancer 74
Renal cell carcinoma 68
Focal adhesion 63
Regulation of actin cytoskeleton 34
Thyroid cancer 32
Salivary secretion 19
Jak-STAT signaling pathway 16
Natural killer cell mediated cytotoxicity 11
Gap junction 11
Endometrial cancer 11
Long-term depression 9
Axon guidance 8
Cytokine-cytokine receptor interaction 8
Chronic myeloid leukemia 7
ErbB signaling pathway 7
Arginine and proline metabolism 6
Maturity onset diabetes of the young 6
Neuroactive ligand-receptor interaction 4
Aldosterone-regulated sodium reabsorption 2
Systemic lupus erythematosus 2
Olfactory transduction 1
Huntington’s disease 1
Chemokine signaling pathway 1
Cardiac muscle contraction 1
Amyotrophic lateral sclerosis (ALS) 1

A few interesting genetic risk factors and possible additional targets for NSCLC were deduced from analysis of the above table of literature including HIF1-α, mIR-31, UBQLN1, ACE, mIR-193a, SRSF1. In addition, glioma, melanoma, colorectal, and prostate and lung cancer share many validated mutations, and possibly similar tumor driver mutations.

KEGGinliteroanalysislungcancer

 please click on graph for larger view

Paper 4. Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing[9]

For full paper and graphical summary please follow the link: http://www.cell.com/cell/abstract/S0092-8674%2812%2901061-6

Highlights

  • Exome and genome characterization of somatic alterations in 183 lung adenocarcinomas
  • 12 somatic mutations/megabase
  • U2AF1, RBM10, and ARID1A are among newly identified recurrently mutated genes
  • Structural variants include activating in-frame fusion of EGFR
  • Epigenetic and RNA deregulation proposed as a potential lung adenocarcinoma hallmark

Summary

Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Paper 5. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer[10]

Highlights

  • Whole exome and transcriptome (RNASeq) sequencing 29 small-cell lung carcinomas
  • High mutation rate 7.4 protein-changing mutations/million base pairs
  • Inactivating mutations in TP53 and RB1
  • Functional mutations in CREBBP, EP300, MLL, PTEN, SLIT2, EPHA7, FGFR1 (determined by literature and database mining)
  • The mutational spectrum seen in human data also present in a Tp53-/- Rb1-/- mouse lung tumor model

 

Curator Graphical Summary of Interesting Findings From the Above Studies

DGRAPHICSUMMARYNSLCSEQPOST

The above figure (please click on figure) represents themes and findings resulting from the aforementioned studies including

questions which will be addressed in Future Posts on this site.

References:

  1. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012, 489(7417):519-525.
  2. A genomics-based classification of human lung tumors. Science translational medicine 2013, 5(209):209ra153.
  3. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J et al: Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 2012, 150(6):1121-1134.
  4. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H et al: RET, ROS1 and ALK fusions in lung cancer. Nature medicine 2012, 18(3):378-381.
  5. Morodomi Y, Takenoyama M, Inamasu E, Toyozawa R, Kojo M, Toyokawa G, Shiraishi Y, Takenaka T, Hirai F, Yamaguchi M et al: Non-small cell lung cancer patients with EML4-ALK fusion gene are insensitive to cytotoxic chemotherapy. Anticancer research 2014, 34(7):3825-3830.
  6. Yoshimura M, Tada Y, Ofuzi K, Yamamoto M, Nakatsura T: Identification of a novel HLA-A 02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene. Oncology reports 2014, 32(1):33-39.
  7. Yang L, Li G, Zhao L, Pan F, Qiang J, Han S: Blocking the PI3K pathway enhances the efficacy of ALK-targeted therapy in EML4-ALK-positive nonsmall-cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2014.
  8. Workman P, van Montfort R: EML4-ALK fusions: propelling cancer but creating exploitable chaperone dependence. Cancer discovery 2014, 4(6):642-645.
  9. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A et al: Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012, 150(6):1107-1120.
  10. Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T et al: Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nature genetics 2012, 44(10):1104-1110.

Other posts on this site which refer to Lung Cancer and Cancer Genome Sequencing include:

Multi-drug, Multi-arm, Biomarker-driven Clinical Trial for patients with Squamous Cell Carcinoma called the Lung Cancer Master Protocol, or Lung-MAP launched by NCI, Foundation Medicine, and Five Pharma Firms

US Personalized Cancer Genome Sequencing Market Outlook 2018 –

Comprehensive Genomic Characterization of Squamous Cell Lung Cancers

International Cancer Genome Consortium Website has 71 Committed Cancer Genome Projects Ongoing

Non-small Cell Lung Cancer drugs – where does the Future lie?

Lung cancer breathalyzer trialed in the UK

Diagnosing Lung Cancer in Exhaled Breath using Gold Nanoparticles

Multi-drug, Multi-arm, Biomarker-driven Clinical Trial for patients with Squamous Cell Carcinoma called the Lung Cancer Master Protocol, or Lung-MAP launched by NCI, Foundation Medicine, and Five Pharma Firms

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Antioxidant micronutrients, such as vitamins and carotenoids, exist in abundance in fruit and vegetables and have been known to contribute to the body’s defence against reactive oxygen species. Numerous epidemiological studies have demonstrated that a high dietary consumption of fruit and vegetables rich in carotenoids or with high serum carotenoid concentrations results in lower risks of certain cancers, diabetes and cardiovascular disease. These epidemiological studies have suggested that antioxidant carotenoids may have a protective effect against diabetes or cardiovascular disease. However, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of these chronic diseases cannot be recommended, because some large randomized controlled trials did not reveal any reduction in cardiovascular events or type 2 diabetes with b-carotene. High doses of carotenoids used in the supplementation studies could have a pro-oxidant effect. Therefore, it is favourable to intake carotenoids from foods through the combination of other nutrients such as vitamins, minerals or phytochemicals, not by supplements.

The metabolic syndrome is a clustering of metabolic abnormalities that increase the risk for diabetes and cardiovascular disease. Typically, it includes excess weight, hyperglycaemia, evaluated blood pressure, low concentration of HDL-cholesterol, and hypertriacylglycerolaemia. This syndrome is emerging as one of the major medical and public health problems in Japan, and persons with this syndrome have an increased risk of morbidity and mortality due to cardiovascular disease and diabetes. Recently, many studies have examined the associations of dietary patterns with the metabolic syndrome and shown that diets rich in fruit and vegetables have been inversely associated with the metabolic syndrome. These previous reports suggest that a high intake of fruit and vegetables may reduce the risk of the metabolic syndrome through the beneficial combination of antioxidants, fibre, minerals, and other phytochemicals. Some recent cross-sectional and case–control studies have shown the associations of serum antioxidant status with the metabolic syndrome. Ford et al. reported that low intake and/or low serum concentrations of vitamins and carotenoids were associated with the risk of the metabolic syndrome. Although very few data are available about the associations of antioxidant carotenoids with the metabolic syndrome, people who have the metabolic syndrome are more likely to have increased oxidative stress than people who do not have this syndrome.

In some recent studies, it has been reported that oxidative stress, which is an imbalance between pro-oxidants and antioxidants, occurs more frequently in metabolic syndrome subjects than in non-metabolic syndrome subjects. Oxidative stress may play a key role in the pathophysiology of diabetes and cardiovascular disease. On the other hand, smoking is a potent oxidative stress in man. This increment of oxidative stress induced by smoking may develop insulin resistance, and increased insulin resistance may result in the clustering of the metabolic abnormality. Therefore, antioxidants could have a beneficial effect on reducing the risk of these conditions in smokers. However, there is limited information about the interaction of serum antioxidant carotenoids and the metabolic syndrome with smoking habit. This study was aimed to investigate the interaction of serum carotenoid concentrations and the metabolic syndrome with smoking. The association of the concentrations of six serum carotenoids, i.e. lutein, lycopene, a-carotene, b-carotene, b-cryptoxanthin and zeaxanthin, with metabolic syndrome status stratified by smoking status was evaluated crosssectionally.

In this study, the associations of the serum carotenoids with the metabolic syndrome stratified by smoking habit were evaluated cross-sectionally. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Inverse associations of serum carotenoids with the metabolic syndrome were more evident among current smokers than non-smokers. These results support that antioxidant carotenoids may have a protective effect against development of the metabolic syndrome, especially in current smokers who are exposed to a potent oxidative stress.

Source References:

http://www.ncbi.nlm.nih.gov/pubmed/18445303

http://www.ncbi.nlm.nih.gov/pubmed/19450371

http://www.ncbi.nlm.nih.gov/pubmed/21216053

http://www.ncbi.nlm.nih.gov/pubmed/19631019

http://www.ncbi.nlm.nih.gov/pubmed/12324189

http://www.ncbi.nlm.nih.gov/pubmed/18689373

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Methylation of the gene F2RL3—which has been linked with platelet activation and inflammation—was lowest in smokers and highest in nonsmokers. Methylation is an important source of variation and regulation in the genome in Epigenetic modification of DNA. In a prospective study in patients with stable coronary heart disease, lower F2RL3 methylation in smokers and former smokers indicated a worse prognosis with excess cardiovascular mortality as well as overall mortality.

The authors found a correlation between F2RL3 methylation intensity and established prognostic markers, including natriuretic peptide, C-reactive protein, and interleukin-6. Current standard medical treatment for coronary artery disease did not affect F2RL3 methylation.

This article was published in European Heart Journal

L. P. Breitling et al., Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease. Eur. Heart J. 17 April 2012

http://eurheartj.oxfordjournals.org/content/early/2012/04/16/eurheartj.ehs091.abstract

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