The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers

Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers.

• Publication year

  2015

• Venue

  Nutrients

• Publication date

  2015-08-28

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/nu7095332PMID 26343715PMCID 4586527
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Lactose intolerance

  2018cited by this paper
• Congenital lactose intolerance is triggered by severe mutations on both alleles of the lactase gene

  2015cited by this paper
• A novel mutation within the lactase gene (LCT): the first report of congenital lactase deficiency diagnosed in Central Europe

  2015cited by this paper
• The effects of consuming probiotic‐fermented milk on the immune system: A review of scientific evidence

  2015cited by this paper
• Dietary supplement use and colorectal cancer risk: A systematic review and meta‐analyses of prospective cohort studies

  2015cited by this paper
• Diet and cancer: risk factors and epidemiological evidence.

  2014cited by this paper
• Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease.

  2014cited by this paper
• Trafficking to the apical and basolateral membranes in polarized epithelial cells.

  2014cited by this paper
• Latitude, sunshine, and human lactase phenotype distributions may contribute to geographic patterns of modern disease: the inflammatory bowel disease model

  2014cited by this paper
• Clinical implications of lactose malabsorption versus lactose intolerance.

  2013cited by this paper
• Lactose malabsorption and colonic fermentations alter host metabolism in rats

  2013cited by this paper
• Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment

  2013cited by this paper
• Fermented Milks and Milk Products as Functional Foods—A Review

  2013cited by this paper
• Diet and nutrient factors in colorectal cancer risk.

  2012cited by this paper
• Food, Nutrition, Physical Activity, and the Prevention of Cancer : a Global Perspective : 食物、栄養、身体活動とがんの予防 : 世界的展望(前篇)

  2012cited by this paper
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  2012cited by this paper
• Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

  2012cited by this paper
• Miglustat-induced intestinal carbohydrate malabsorption is due to the inhibition of α-glucosidases, but not β-galactosidases

  2012cited by this paper
• Herders of Indian and European cattle share their predominant allele for lactase persistence.

  2012cited by this paper
• High prevalence of colonization with Staphylococcus aureus clone USA300 at multiple body sites among sexually transmitted disease clinic patients: an unrecognized reservoir.

  2012cited by this paper
• Genetic variation in the lactase gene, dairy product intake and risk for prostate cancer in the European Prospective Investigation into Cancer and Nutrition

  2012cited by this paper
• Review: Management of postprandial diarrhea syndrome.

  2012cited by this paper
• Impact of cows’ milk estrogen on cancer risk

  2012cited by this paper
• Lack of biologically active estrogens in commercial cow milk.

  2012cited by this paper
• The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

  2012cited by this paper
• The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

  2011cited by this paper
• Lactose-Free Milk Protein-Based Infant Formula: Impact on Growth and Gastrointestinal Tolerance in Infants

  2011cited by this paper
• Milk and the risk and progression of cancer.

  2011influential reference
• Vitamin D and intestinal calcium absorption.

  2011cited by this paper
• Lactose intolerance and health.

  2010cited by this paper
• Determinants of geographic patterns of diseases: interaction of lactose/lactase status and sunshine exposure.

  2010cited by this paper
• National Institutes of Health Consensus Development Conference: Lactose Intolerance and Health

  2010cited by this paper
• Estrone and 17beta-estradiol concentrations in pasteurized-homogenized milk and commercial dairy products.

  2010cited by this paper
• Structural Basis for Substrate Selectivity in Human Maltase-Glucoamylase and Sucrase-Isomaltase N-terminal Domains*

  2010cited by this paper
• LCT-13910C>T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy.

  2010cited by this paper
• Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD)

  2009cited by this paper
• The Role of Galectins in Protein Trafficking

  2009cited by this paper
• On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola

  2009cited by this paper
• A systematic review of the effect of diet in prostate cancer prevention and treatment.

  2009cited by this paper
• Impact of molecularly defined hypolactasia, self-perceived milk intolerance and milk consumption on bone mineral density in a population sample in Northern Europe

  2009cited by this paper
• Screening of variants for lactase persistence/non-persistence in populations from South Africa and Ghana

  2009cited by this paper
• IBS or intolerance?

  2009cited by this paper
• Positive Glucose Breath Testing is More Prevalent in Patients With IBS-like Symptoms Compared With Controls of Similar Age and Gender Distribution

  2009cited by this paper
• Impaired trafficking and subcellular localization of a mutant lactase associated with congenital lactase deficiency.

  2009influential reference
• Lactase persistence-related genetic variant: population substructure and health outcomes

  2009cited by this paper
• Multiple Rare Variants as a Cause of a Common Phenotype: Several Different Lactase Persistence Associated Alleles in a Single Ethnic Group

  2009cited by this paper
• Dairy product consumption and the risk of prostate cancer

  2009cited by this paper
• A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome.

  2009cited by this paper
• Probiotic fermented milks: present and future.

  2009cited by this paper
• Structural Hierarchy of Regulatory Elements in the Folding and Transport of an Intestinal Multidomain Protein*

  2009cited by this paper
• Quantitative measurement of endogenous estrogen metabolites, risk-factors for development of breast cancer, in commercial milk products by LC-MS/MS.

  2009cited by this paper
• Weight regain after Roux-en-Y: a significant 20% complication related to PYY.

  2008cited by this paper
• Survey of retail milk composition as affected by label claims regarding farm-management practices.

  2008cited by this paper
• Genetics of Lactase Persistence and Lactose Intolerance

  2008cited by this paper
• Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population

  2008cited by this paper
• Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective, World Cancer Research Fund/American Institute for Cancer Research. American Institute for Cancer Research, Washington, D.C (2007), ISBN: 978-0-9722522-2-5

  2008cited by this paper
• Molecular differentiation of congenital lactase deficiency from adult-type hypolactasia.

  2008cited by this paper
• New insights into calcium, dairy and colon cancer.

  2008cited by this paper
• Lactose intolerance in prostate cancer patients: Incidence and associated factors

  2008cited by this paper
• 17Beta-estradiol and estrone concentrations in plasma and milk during bovine pregnancy.

  2008cited by this paper
• Estrogen plays a critical role in AAV2-mediated gene transfer in ovarian cancer

  2008cited by this paper
• Lactase Persistence, Dietary Intake of Milk, and the Risk for Prostate Cancer in Sweden and Finland

  2007cited by this paper
• Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies.

  2007cited by this paper
• Expression of Rotavirus NSP4 Alters the Actin Network Organization through the Actin Remodeling Protein Cofilin

  2007cited by this paper
• Genotyping of the Lactase-Phlorizin Hydrolase C/T-13910 Polymorphism by Means of a New Rapid Denaturing High-Performance Liquid Chromatography-Based Assay in Healthy Subjects and Colorectal Cancer Patients

  2007cited by this paper
• Convergent adaptation of human lactase persistence in Africa and Europe

  2007cited by this paper
• An NSP4‐dependant mechanism by which rotavirus impairs lactase enzymatic activity in brush border of human enterocyte‐like Caco‐2 cells

  2007cited by this paper
• Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose‐intolerant subjects

  2007cited by this paper
• Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective

  2007cited by this paper
• Colonic fermentation may play a role in lactose intolerance in humans.

  2006cited by this paper
• Relationship Between Calcium, Lactose, Vitamin D, and Dairy Products and Ovarian Cancer

  2006cited by this paper
• Requirement for galectin-3 in apical protein sorting.

  2006cited by this paper
• Evaluation of Relationships Among National Colorectal Cancer Mortality Rates, Genetic Lactase Non-Persistence Status, and Per Capita Yearly Milk and Milk Product Consumption

  2006cited by this paper
• Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer

  2006cited by this paper
• Naturally occurring estrogens in processed milk and in raw milk (from gestated cows).

  2006cited by this paper
• A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

  2006cited by this paper
• Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency.

  2006cited by this paper
• Diet After Diagnosis and the Risk of Prostate Cancer Progression, Recurrence, and Death (United States)

  2006cited by this paper
• Lactose Intolerance in Infants, Children, and Adolescents

  2006cited by this paper
• The Effect of Lactose Maldigestion on the Relationship Between Dairy Food Intake and Colorectal Cancer: A Systematic Review

  2006cited by this paper
• Rotavirus NSP4: A Multifunctional Viral Enterotoxin

  2005cited by this paper
• T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro.

  2005cited by this paper
• The C/C−13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population

  2005cited by this paper
• Lactase persistence and ovarian carcinoma risk in Finland, Poland and Sweden

  2005cited by this paper
• Systemic lactose intolerance: a new perspective on an old problem

  2005cited by this paper
• The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.

  2005cited by this paper
• Lactose malabsorption and IBS

  2004cited by this paper
• Estrogen: one of the risk factors in milk for prostate cancer.

  2004cited by this paper
• A genetic test which can be used to diagnose adult-type hypolactasia in children

  2004cited by this paper
• New approaches to the role of diet in the prevention of cancers of the alimentary tract.

  2004cited by this paper
• A prospective study of dietary lactose and ovarian cancer

  2004cited by this paper
• Genetics of lactase persistence and lactose intolerance.

  2003cited by this paper
• Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element.

  2003cited by this paper
• Intracellular survival of Staphylococcus aureus within cultured enterocytes.

  2003cited by this paper
• Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia

  2003cited by this paper
• Distinct cytoskeletal tracks direct individual vesicle populations to the apical membrane of epithelial cells.

  2003cited by this paper
• Enhanced weight gain in preterm infants receiving lactase-treated feeds: a randomized, double-blind, controlled trial.

  2002cited by this paper
• The Prosequence of Human Lactase-Phlorizin Hydrolase Modulates the Folding of the Mature Enzyme*

  2002influential reference
• Identification of a variant associated with adult-type hypolactasia

  2002cited by this paper
• Overcoming the barrier of lactose intolerance to reduce health disparities.

  2002cited by this paper

• [Lactose: beneficial or harmful? Evidence-based dietary approaches].

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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
• Longitudinal prospective anthropometric evaluation in Caucasian prepubertal children with lactose intolerance

  2023cites this paper
• Intolerance to Milk Lactose, Diagnostic Tests and Dietary Management: A Recent Update

  2022cites this paper
• The Association of Lactose Intolerance With Colon and Gastric Cancers: Friend or Foe?

  2022influential citation
• World Journal of Clinical Pediatrics

  2022cites this paper
• Lactase persistence phenotype and genotype in Iranian Mazani-Shahmirzadi and Afghan Hazara ethnicities.

  2022cites this paper
• Cow’s milk-induced gastrointestinal disorders: From infancy to adulthood

  2022cites this paper
• Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment.

  2021cites this paper
• Disorders of Carbohydrate Metabolism

  2021cites this paper
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  2021cites this paper
• Identification of Novel Mutations in LCT-Gene of Pakistani Patients with Lactose Non-persistence

  2020cites this paper
• Digestive fate of polyphenols: updated view of the influence of chemical structure and the presence of cell wall material

  2020cites this paper
• Routine disaccharidase testing: are we there yet?

  2020cites this paper
• Human health effects of lactose consumption as food and drug ingredient.

  2020cites this paper
• Gut dysbacteriosis and intestinal disease: mechanism and treatment

  2020cites this paper
• A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine

  2020cites this paper
• Association between dietary intake and risk of ovarian cancer: a systematic review and meta-analysis

  2020cites this paper
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  2020cites this paper
• Prospects of fermented milk products in children with primary hypolactasia of the adult type

  2020influential citation
• Characterization of Cu-only SOD Repeat Protein in Zebrafish (Danio rerio)

  2020cites this paper
• Dairy Ethics

  2019cites this paper
• Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives

  2019influential citation
• Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management

  2019cites this paper
• Structure of beta-glucosidase A from Paenibacillus polymyxa complexed with a monovalent inhibitor

  2019cites this paper
• Saccharomyces boulardii CNCM I-745 — die medizinische Hefe verbessert die Funktion intestinaler Enzyme

  2019cites this paper
• Structural basis of the inhibition of GH1 β-glucosidases by multivalent pyrrolidine iminosugars.

  2019cites this paper
• The Importance of Lactose in the Human Diet: Outcomes of a Mexican Consensus Meeting

  2019cites this paper
• Digestion, absorption, metabolism, and physiological effects of lactose

  2019cites this paper
• Lactose intolerance

  2018cites this paper
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  2018cites this paper
• ABM Clinical Protocol #7: Model Maternity Policy Supportive of Breastfeeding

  2018cites this paper
• Lactose malabsorption and intolerance: a review.

  2018cites this paper
• Does primary lactase deficiency reduce bone mineral density in postmenopausal women? A systematic review and meta-analysis

  2018cites this paper
• Challenge in interpretation of Mendelian randomization studies using lactase persistence as instrumental variable

  2018cites this paper
• Milk and Chronic-Degenerative Diseases: Main Components and Potential Mechanisms

  2017cites this paper
• Lactose Intolerance and Inheritance of Lactase Persistence: A Review

  2017cites this paper
• Lactose Intolerance and Colorectal Cancer

  2017cites this paper
• How dairy food affects prostate cancer?- a literature review

  year unknowncites this paper