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Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study.
Pubmed ID
33653810 (View this publication on the PubMed website)
Digital Object Identifier
Cancer Epidemiol Biomarkers Prev. 2021 May; Volume 30 (Issue 5): Pages 953-964
Dimou N, Yarmolinsky J, Bouras E, Tsilidis KK, Martin RM, Lewis SJ, Gram IT, Bakker MF, Brenner H, Figueiredo JC, Fortner RT, Gruber SB, van Guelpen B, Hsu L, Kaaks R, Kweon SS, Lin Y, Lindor NM, Newcomb PA, Sánchez MJ, more Severi G, Tindle HA, Tumino R, Weiderpass E, Gunter MJ, Murphy N
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
  • Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University Utrecht, Utrecht, the Netherlands.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Center for Precision Medicine, City of Hope National Medical Center, Duarte, California. more
  • Department of Radiation Sciences, Oncology Unit, Umea University, Umea, Sweden.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
  • Department of Health Science Research, Mayo Clinic, Scottsdale, Arizona.
  • Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
  • CESP UMR1018, Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Villejuif, France.
  • General Internal Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee.
  • Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7) Ragusa, Ragusa, Italy.
  • Office of the Director, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

BACKGROUND: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer.

METHODS: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls).

RESULTS: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00-1.26; P = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor-positive and estrogen receptor-negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04-1.40; P = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11-1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07-1.73; P = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90-1.14; P = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86-1.10; P = 0.68).

CONCLUSIONS: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer.

IMPACT: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.

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