Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

Larsson, Susanna C.; Carter, Paul; Kar, Siddhartha; Vithayathil, Mathew; Mason, Amy M.; Michaëlsson, Karl; Burgess, Stephen

doi:10.1371/journal.pmed.1003178

Cited by 143 publications

(133 citation statements)

References 46 publications

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“…This could be the case for BMI, age at menopause and menarche, or height, which have been causally associated with breast cancer risk [ 58 ]. For other risk factors such as T2DM or smoking, MR studies of incidence could not provide evidence for a causal association [ 59 , 60 ], which makes these genetic instruments less likely to be affected by selection bias.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer risk factors and their effects on survival: a Mendelian randomisation study

Escala-Garcia

Morra

Canisius

et al. 2020

BMC Med

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Background Observational studies have investigated the association of risk factors with breast cancer prognosis. However, the results have been conflicting and it has been challenging to establish causality due to potential residual confounding. Using a Mendelian randomisation (MR) approach, we aimed to examine the potential causal association between breast cancer-specific survival and nine established risk factors for breast cancer: alcohol consumption, body mass index, height, physical activity, mammographic density, age at menarche or menopause, smoking, and type 2 diabetes mellitus (T2DM). Methods We conducted a two-sample MR analysis on data from the Breast Cancer Association Consortium (BCAC) and risk factor summary estimates from the GWAS Catalog. The BCAC data included 86,627 female patients of European ancestry with 7054 breast cancer-specific deaths during 15 years of follow-up. Of these, 59,378 were estrogen receptor (ER)-positive and 13,692 were ER-negative breast cancer patients. For the significant association, we used sensitivity analyses and a multivariable MR model. All risk factor associations were also examined in a model adjusted by other prognostic factors. Results Increased genetic liability to T2DM was significantly associated with worse breast cancer-specific survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03–1.17, P value [P] = 0.003). There were no significant associations after multiple testing correction for any of the risk factors in the ER-status subtypes. For the reported significant association with T2DM, the sensitivity analyses did not show evidence for violation of the MR assumptions nor that the association was due to increased BMI. The association remained significant when adjusting by other prognostic factors. Conclusions This extensive MR analysis suggests that T2DM may be causally associated with worse breast cancer-specific survival and therefore that treating T2DM may improve prognosis.

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Section: Discussionmentioning

confidence: 99%

Breast cancer risk factors and their effects on survival: a Mendelian randomisation study

Escala-Garcia

Morra

Canisius

et al. 2020

BMC Med

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“…In the present analysis, we included 367,643 unrelated participants of European ancestry to diminish population stratification bias and used follow-up data to March 31, 2017. Classification of each cancer site has been reported previously [ 23 ]. Analyses of genotype-cancer associations were done only in women for breast cancer and only in men for prostate cancer.…”

Section: Methodsmentioning

confidence: 99%

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

Larsson

Mason

Kar

et al. 2020

BMC Med

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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.

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“…We additionally investigated the associations of education level and intelligence with modifiable health-related risk factors. Given that obesity and smoking influence the risk of many diseases 21 – 25 , we examined whether these two factors mediate the pathway from education to health outcomes.…”

Section: Introductionmentioning

confidence: 99%

Genetically predicted education attainment in relation to somatic and mental health

Yuan

Xiong

Michaëlsson

et al. 2021

Sci Rep

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A deeper understanding of the causal links from education level to health outcomes may shed a light for disease prevention. In the present Mendelian randomization study, we found that genetically higher education level was associated with lower risk of major mental disorders and most somatic diseases, independent of intelligence. Higher education level adjusted for intelligence was associated with lower risk of suicide attempts, insomnia, major depressive disorder, heart failure, stroke, coronary artery disease, lung cancer, breast cancer, type 2 diabetes and rheumatoid arthritis but with higher risk of obsessive–compulsive disorder, anorexia nervosa, anxiety, bipolar disorder and prostate cancer. Higher education level was associated with reduced obesity and smoking, which mediated quite an extent of the associations between education level and health outcomes. These findings emphasize the importance of education to reduce the burden of common diseases.

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Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants

Cited by 143 publications

References 46 publications

Breast cancer risk factors and their effects on survival: a Mendelian randomisation study

Breast cancer risk factors and their effects on survival: a Mendelian randomisation study

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

Genetically predicted education attainment in relation to somatic and mental health

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