Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2020

01-12-2020 | Prostate Cancer | Research article

Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study

Authors: Susanna C. Larsson, Amy M. Mason, Siddhartha Kar, Mathew Vithayathil, Paul Carter, John A. Baron, Karl Michaëlsson, Stephen Burgess

Published in: BMC Medicine | Issue 1/2020

Login to get access

Abstract

Background

Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption.

Methods

We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose.

Results

Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91–0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94–1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00–1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99–1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01–1.13; P = 0.026).

Conclusions

Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.
Literature
1.
2.
Cho E, Smith-Warner SA, Spiegelman D, Beeson WL, van den Brandt PA, Colditz GA, Folsom AR, et al. Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst. 2004;96:1015–22.PubMedCrossRef
3.
Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, Norat T. Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol. 2012;23:37–45.PubMedCrossRef
4.
Thorning TK, Raben A, Tholstrup T, Soedamah-Muthu SS, Givens I, Astrup A. Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence. Food Nutr Res. 2016;60:32527.PubMedCrossRef
5.
Vieira AR, Abar L, Chan DSM, Vingeliene S, Polemiti E, Stevens C, Greenwood D, et al. Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Ann Oncol. 2017;28:1788–802.PubMedCrossRef
6.
Barrubes L, Babio N, Becerra-Tomas N, Rosique-Esteban N, Salas-Salvado J. Association between dairy product consumption and colorectal cancer risk in adults: a systematic review and meta-analysis of epidemiologic studies. Adv Nutr. 2019;10:S190–211.PubMedPubMedCentralCrossRef
7.
World Cancer Research Fund/American Institute for Cancer Research. Diet, nutrition, physical activity and cancer: a global perspective. The Third Expert Report.: World Cancer Research Fund International; 2018.
8.
Veettil SK, Ching SM, Lim KG, Saokaew S, Phisalprapa P, Chaiyakunapruk N. Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials. Medicine (Baltimore). 2017;96:e7661.CrossRef
9.
Heine-Broring RC, Winkels RM, Renkema JM, Kragt L, van Orten-Luiten AC, Tigchelaar EF, Chan DS, et al. Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies. Int J Cancer. 2015;136:2388–401.PubMedCrossRef
10.
Chau R, Dashti SG, Ait Ouakrim D, Buchanan DD, Clendenning M, Rosty C, Winship IM, et al. Multivitamin, calcium and folic acid supplements and the risk of colorectal cancer in Lynch syndrome. Int J Epidemiol. 2016;45:940–53.PubMedPubMedCentralCrossRef
11.
Wu J, Yu Y, Huang L, Li Z, Guo P, Xu YW. Dairy product consumption and bladder cancer risk: a meta-analysis. Nutr Cancer. 2020;72:377–85.PubMedCrossRef
12.
Bermejo LM, Lopez-Plaza B, Santurino C, Cavero-Redondo I, Gomez-Candela C. Milk and dairy product consumption and bladder cancer risk: a systematic review and meta-analysis of observational studies. Adv Nutr. 2019;10:S224–38.PubMedPubMedCentralCrossRef
13.
Wu J, Zeng R, Huang J, Li X, Zhang J, Ho JC, Zheng Y. Dietary protein sources and incidence of breast cancer: a dose-response meta-analysis of prospective studies. Nutrients. 2016;8.
14.
Zang J, Shen M, Du S, Chen T, Zou S. The association between dairy intake and breast cancer in Western and Asian populations: a systematic review and meta-analysis. J Breast Cancer. 2015;18:313–22.PubMedPubMedCentralCrossRef
15.
Aune D, Navarro Rosenblatt DA, Chan DS, Vieira AR, Vieira R, Greenwood DC, Vatten LJ, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101:87–117.PubMedCrossRef
16.
Lopez-Plaza B, Bermejo LM, Santurino C, Cavero-Redondo I, Alvarez-Bueno C, Gomez-Candela C. Milk and dairy product consumption and prostate cancer risk and mortality: an overview of systematic reviews and meta-analyses. Adv Nutr. 2019;10:S212–23.PubMedPubMedCentralCrossRef
17.
Markozannes G, Tzoulaki I, Karli D, Evangelou E, Ntzani E, Gunter MJ, Norat T, et al. Diet, body size, physical activity and risk of prostate cancer: an umbrella review of the evidence. Eur J Cancer. 2016;69:61–9.PubMedCrossRef
18.
Godos J, Tieri M, Ghelfi F, Titta L, Marventano S, Lafranconi A, Gambera A, et al. Dairy foods and health: an umbrella review of observational studies. Int J Food Sci Nutr. 2020;71:138–51.PubMedCrossRef
19.
Genkinger JM, Hunter DJ, Spiegelman D, Anderson KE, Arslan A, Beeson WL, Buring JE, et al. Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomark Prev. 2006;15:364–72.CrossRef
20.
Vissers LET, Sluijs I, van der Schouw YT, Forouhi NG, Imamura F, Burgess S, Barricarte A, et al. Dairy product intake and risk of type 2 diabetes in EPIC-InterAct: a Mendelian randomization study. Diabetes Care. 2019;42:568–75.PubMedCrossRef
21.
Bergholdt HKM, Larsen MK, Varbo A, Nordestgaard BG, Ellervik C. Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis. J Intern Med. 2018;284:254–69.PubMedCrossRef
22.
Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.PubMedPubMedCentralCrossRef
23.
Larsson SC, Carter P, Kar S, Vithayathil M, Mason AM, Michaelsson K, Burgess S. Smoking, alcohol consumption, and cancer: a mendelian randomisation study in UK Biobank and international genetic consortia participants. PLoS Med. 2020;17:e1003178.PubMedPubMedCentralCrossRef
24.
25.
Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui S, Kar S, Lemacon A, et al. Association analysis identifies 65 new breast cancer risk loci. Nature. 2017;551:92–4.PubMedPubMedCentralCrossRef
26.
Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, Dadaev T, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet. 2018;50:928–36.PubMedPubMedCentralCrossRef
27.
Smith CE, Coltell O, Sorli JV, Estruch R, Martinez-Gonzalez MA, Salas-Salvado J, Fito M, et al. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization. Sci Rep. 2016;6:33188.PubMedPubMedCentralCrossRef
28.
Machiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31:3555–7.PubMedPubMedCentralCrossRef
29.
30.
Larsson SC, Andersson SO, Johansson JE, Wolk A. Cultured milk, yogurt, and dairy intake in relation to bladder cancer risk in a prospective study of Swedish women and men. Am J Clin Nutr. 2008;88:1083–7.PubMedCrossRef
31.
32.
Tarabra E, Pazienza P, Borghesio E, Actis GC, Tappero G, Framarin L, Ayoubi M, et al. LCT-13910C>T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy. Dig Liver Dis. 2010;42:741–3.PubMedCrossRef
33.
Travis RC, Appleby PN, Siddiq A, Allen NE, Kaaks R, Canzian F, Feller S, et al. Genetic variation in the lactase gene, dairy product intake and risk for prostate cancer in the European prospective investigation into cancer and nutrition. Int J Cancer. 2013;132:1901–10.PubMedCrossRef
34.
Torniainen S, Hedelin M, Autio V, Rasinpera H, Balter KA, Klint A, Bellocco R, et al. Lactase persistence, dietary intake of milk, and the risk for prostate cancer in Sweden and Finland. Cancer Epidemiol Biomark Prev. 2007;16:956–61.CrossRef
35.
36.
Baron JA, Barry EL, Mott LA, Rees JR, Sandler RS, Snover DC, Bostick RM, et al. A trial of calcium and vitamin D for the prevention of colorectal adenomas. N Engl J Med. 2015;373:1519–30.PubMedPubMedCentralCrossRef
37.
Norat T, Riboli E. Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence. Eur J Clin Nutr. 2003;57:1–17.PubMedCrossRef
38.
Pufulete M. Intake of dairy products and risk of colorectal neoplasia. Nutr Res Rev. 2008;21:56–67.PubMedCrossRef
39.
Yang W, Liu L, Masugi Y, Qian ZR, Nishihara R, Keum N, Wu K, et al. Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR). Gut. 2018;67:1475–83.PubMedCrossRef
40.
Mandle HB, Jahan FA, Bostick RM, Baron JA, Barry EL, Yacoub R, Merrill J, et al. Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients. Mol Carcinog. 2019;58:1279–90.PubMedPubMedCentral
41.
Tsuda H, Kozu T, Iinuma G, Ohashi Y, Saito Y, Saito D, Akasu T, et al. Cancer prevention by bovine lactoferrin: from animal studies to human trial. Biometals. 2010;23:399–409.PubMedCrossRef
42.
43.
Larsson SC, Bergkvist L, Wolk A. High-fat dairy food and conjugated linoleic acid intakes in relation to colorectal cancer incidence in the Swedish Mammography Cohort. Am J Clin Nutr. 2005;82:894–900.PubMedCrossRef
44.
Kozu T, Iinuma G, Ohashi Y, Saito Y, Akasu T, Saito D, Alexander DB, et al. Effect of orally administered bovine lactoferrin on the growth of adenomatous colorectal polyps in a randomized, placebo-controlled clinical trial. Cancer Prev Res (Phila). 2009;2:975–83.CrossRef
45.
Liu Y, Ajami NJ, El-Serag HB, Hair C, Graham DY, White DL, Chen L, et al. Dietary quality and the colonic mucosa-associated gut microbiome in humans. Am J Clin Nutr. 2019;110:701–12.PubMedPubMedCentralCrossRef
46.
Guantario B, Giribaldi M, Devirgiliis C, Finamore A, Colombino E, Capucchio MT, Evangelista R, et al. A comprehensive evaluation of the impact of bovine milk containing different beta-casein profiles on gut health of ageing mice. Nutrients. 2020;12:2147.PubMedCentralCrossRef
47.
Harrison S, Lennon R, Holly J, Higgins JPT, Gardner M, Perks C, Gaunt T, et al. Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis. Cancer Causes Control. 2017;28:497–528.PubMedPubMedCentralCrossRef
48.
Larsson SC, Carter P, Vithayathil M, Kar S, Mason AM, Burgess S. Insulin-like growth factor-1 and site-specific cancers: a Mendelian randomization study. Cancer Med. 2020.
49.
Wilson KM, Shui IM, Mucci LA, Giovannucci E. Calcium and phosphorus intake and prostate cancer risk: a 24-y follow-up study. Am J Clin Nutr. 2015;101:173–83.PubMedCrossRef
50.
Bergholdt HK, Nordestgaard BG, Varbo A, Ellervik C. Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults. Int J Epidemiol. 2015;44:587–603.PubMedCrossRef
51.
Mendelian Randomization of Dairy Consumption Working G. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies. Clin Chem. 2018;64:183–91.CrossRef
52.
Yang Q, Lin SL, Au Yeung SL, Kwok MK, Xu L, Leung GM, Schooling CM. Genetically predicted milk consumption and bone health, ischemic heart disease and type 2 diabetes: a Mendelian randomization study. Eur J Clin Nutr. 2017;71:1008–12.PubMedCrossRef
53.
Hartwig FP, Horta BL, Smith GD, de Mola CL, Victora CG. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis. Int J Epidemiol. 2016(45):1573–87.
54.
Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chu AY, et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet. 2014;46:1173–86.PubMedPubMedCentralCrossRef
55.
Cornish AJ, Law PJ, Timofeeva M, Palin K, Farrington SM, Palles C, Jenkins MA, et al. Modifiable pathways for colorectal cancer: a mendelian randomisation analysis. Lancet Gastroenterol Hepatol. 2020;5:55–62.PubMedCrossRef
56.
Lai FY, Nath M, Hamby SE, Thompson JR, Nelson CP, Samani NJ. Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis. BMC Med. 2018;16:187.PubMedPubMedCentralCrossRef
Metadata
Title
Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study
Authors
Susanna C. Larsson
Amy M. Mason
Siddhartha Kar
Mathew Vithayathil
Paul Carter
John A. Baron
Karl Michaëlsson
Stephen Burgess
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-01839-9

Other articles of this Issue 1/2020

BMC Medicine 1/2020 Go to the issue

Review

The impact of maternal and early life malnutrition on health: a diet-microbe perspective

Opinion

Functional somatic disorders: discussion paper for a new common classification for research and clinical use

Research article

Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study

Opinion

Patient and public involvement in research: from tokenistic box ticking to valued team members

Research article

A single-center, retrospective study of COVID-19 features in children: a descriptive investigation

Research article

Allocation of intensive care resources during an infectious disease outbreak: a rapid review to inform practice