Diabetes, Glycated Hemoglobin, and Risk of Cancer in the UK Biobank Study

Importance Efforts are underway to incorporate retinal neurodegeneration in the diabetic retinopathy severity scale. However, there is no established measure to quantify diabetic retinal neurodegeneration (DRN). Objective We compared total retinal, macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness among participants with and without diabetes (DM) in a population-based cohort. Design/setting/participants Cross-sectional analysis, using the UK Biobank data resource. Separate general linear mixed models (GLMM) were created using DM and glycated hemoglobin as predictor variables for retinal thickness. Sub-analyses included comparing thickness measurements for patients with no/mild diabetic retinopathy (DR) and evaluating factors associated with retinal thickness in participants with and without diabetes. Factors found to be significantly associated with DM or thickness were included in a multiple GLMM. Exposure Diagnosis of DM was determined via self-report of diagnosis, medication use, DM-related complications or glycated hemoglobin level of ≥ 6.5%. Main outcomes and measures Total retinal, mRNFL and GC-IPL thickness. Results 74,422 participants (69,985 with no DM; 4,437 with DM) were included. Median age was 59 years, 46% were men and 92% were white. Participants with DM had lower total retinal thickness (-4.57 μm, 95% CI: -5.00, -4.14; p<0.001), GC-IPL thickness (-1.73 μm, 95% CI: -1.86, -1.59; p<0.001) and mRNFL thickness (-0.68 μm, 95% CI: -0.81, -0.54; p<0.001) compared to those without DM. After adjusting for co-variates, in the GLMM, total retinal thickness was 1.99 um lower (95% CI: -2.47, -1.50; p<0.001) and GC-IPL was 1.02 μm lower (95% CI: -1.18, -0.87; p<0.001) among those with DM compared to without. mRNFL was no longer significantly different (p = 0.369). GC-IPL remained significantly lower, after adjusting for co-variates, among those with DM compared to those without DM when including only participants with no/mild DR (-0.80 μm, 95% CI: -0.98, -0.62; p<0.001). Total retinal thickness decreased 0.40 μm (95% CI: -0.61, -0.20; p<0.001), mRNFL thickness increased 0.20 μm (95% CI: 0.14, 0.27; p<0.001) and GC-IPL decreased 0.26 μm (95% CI: -0.33, -0.20; p<0.001) per unit increase in A1c after adjusting for co-variates. Among participants with diabetes, age, DR grade, ethnicity, body mass index, glaucoma, spherical equivalent, and visual acuity were significantly associated with GC-IPL thickness. Conclusion GC-IPL was thinner among participants with DM, compared to without DM. This difference persisted after adjusting for confounding variables and when considering only those with no/mild DR. This confirms that GC-IPL thinning occurs early in DM and can serve as a useful marker of DRN.

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Diet and risk of cancer and other diseases in the UK Biobank

http://isrctn.com/ ◽

10.1186/isrctn10125697 ◽

2017 ◽

Author(s):

Kathryn Bradbury

Keyword(s):

Uk Biobank ◽

The Uk ◽

Risk Of Cancer

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A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort

Cancer Medicine ◽

10.1002/cam4.4097 ◽

2021 ◽

Author(s):

Sofia Christakoudi ◽

Konstantinos K. Tsilidis ◽

Evangelos Evangelou ◽

Elio Riboli

Keyword(s):

Body Shape ◽

Shape Index ◽

Uk Biobank ◽

The Uk ◽

Risk Of Cancer ◽

A Body Shape Index

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Alcohol causes an increased risk of head and neck but not breast cancer in individuals from the UK Biobank study: A Mendelian randomisation analysis

10.1101/19002832 ◽

2019 ◽

Author(s):

Nathan Ingold ◽

Hasnat A Amin ◽

Fotios Drenos

Keyword(s):

Breast Cancer ◽

Alcohol Consumption ◽

Head And Neck ◽

Causal Effect ◽

Head And Neck Cancers ◽

Mendelian Randomisation ◽

Uk Biobank ◽

Increased Risk ◽

The Uk ◽

Risk Of Cancer

ABSTACTAlcohol intake and the risk of various types of cancers have been previously correlated. Correlation though does not always mean that a causal relationship between the two is present. Excessive alcohol consumption is also correlated with other lifestyle factors and behaviours, such as smoking and increased adiposity, that also affect the risk of cancer and make the identification and estimation of the causal effect of alcohol on cancer difficult. Here, using individual level data for 322,193 individuals from the UK Biobank, we report the observational and causal effects of alcohol consumption on types of cancer previously suggested as correlated to alcohol. Alcohol was observationally associated with cancers of the lower digestive system, head and neck and breast cancer. No associations were observed when we considered those keeping alcohol consumption below the recommended threshold of 14 units/week. When Mendelian randomisation was used to assess the causal effect of alcohol on cancer, we found that increasing alcohol consumption, especially above the recommended level, was causal to head and neck cancers but not breast cancer. Our results where replicated using a two sample MR method and data from the much larger COGS genome wide analysis of breast cancer. We conclude that alcohol is causally related to head and neck cancers, especially cancer of larynx, but the observed association with breast cancer are likely due to confounding. The suggested threshold of 14 units/week appears suitable to manage the risk of cancer due to alcohol.

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The role of genetic polymorphisms in endolysosomal ion channels TPC2 and P2RX4 in cancer pathogenesis, prognosis, and diagnosis: a genetic association in the UK Biobank

npj Genomic Medicine ◽

10.1038/s41525-021-00221-9 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Abeer F. Alharbi ◽

John Parrington

Keyword(s):

Prostate Cancer ◽

Ion Channels ◽

Genetic Variants ◽

Cancer Recurrence ◽

Malignant Neoplasms ◽

Uk Biobank ◽

Cancer Subtypes ◽

Increased Risk ◽

The Uk ◽

Risk Of Cancer

AbstractRecent studies have implicated important roles for endolysosomal ion channels in cancer biology. We used UK Biobank data to characterise the relationships between genetic variants in two genes coding for endolysosomal ion channels—i.e. TPCN2 and P2RX4—and cancer in terms of the definition of tumour types, susceptibility, and prognosis. We investigated these relationships at both global and local levels with regard to specific types of cancer, including malignant neoplasms of the brain, breast, bronchus, lung, colon, lymphoid and haematopoietic systems, skin, ovary, prostate, rectum, thyroid gland, lip, oral cavity, pharynx, and urinary tract. Apart from rs3829241 (p value < 0.05), all the genetic variants were in Hardy–Weinberg equilibrium. We included 468,436 subjects in the analysis and stratified them into two major cohorts: cancer-free controls (385,253) and cancer cases (83,183). For the first time, we report novel associations between genetic variants of TPCN2 and P2RX4 and cancer/cancer subtypes in the UK Biobank’s population. Genotype GG in TPCN2 rs3750965 was significantly associated with a decreased risk of cancer and an increased risk of lip, oral cavity, and pharynx cancer and cancer recurrence in patients with prostate cancer, and genotypes GA/GG were associated with a significantly lower risk of developing various malignant neoplasms (involving melanoma, prostate, mesothelial, and soft tissues). rs35264875:TA was associated with a high risk of cancer at the global level, with subtypes of cancer at the local level (including breast, colon, prostate, and stated or presumed primary cancer of lymphoid, haematopoietic, and related tissue), and with a significantly low risk of cancer metastasis. rs72932540:GA was associated with a higher incidence of cancer/cancer subtypes (including breast, melanoma, and rectal cancer), and genotypes GA/GG were associated with an increased risk of prostate cancer. The P2RX4 rs25644 allele GG was associated with a high risk of prostate cancer, whereas it was associated with a low risk of cancer recurrence in patients with prostate cancer. Genotypes GA/GG in rs28360472 were associated with an increased risk of breast, mesothelial, and soft tissue cancers but with a decreased risk of colon cancer. We also provide insights into the pathophysiological contributions made by these significant polymorphisms to cancer/cancer subtypes and their effects on expression or channel activity. Further investigations of these genetic variants could help identify novel cancer biomarkers and facilitate the development of new diagnostic and therapeutic strategies. This would constitute a further step towards personalised cancer care.

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Diabetes, Glycated Hemoglobin, and the Risk of Myocardial Infarction in Women and Men: A Prospective Cohort Study of the UK Biobank

Diabetes Care ◽

10.2337/dc19-2363 ◽

2020 ◽

Vol 43 (9) ◽

pp. 2050-2059 ◽

Cited By ~ 1

Author(s):

Marit de Jong ◽

Mark Woodward ◽

Sanne A.E. Peters

Keyword(s):

Myocardial Infarction ◽

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Glycated Hemoglobin ◽

Uk Biobank ◽

The Uk

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P10 Association of cardiovascular disease and risk of cancer: Prospective cohort study from the UK Biobank

10.1136/heartjnl-2020-scf.20 ◽

2020 ◽

Author(s):

Solange Parra-Soto ◽

Jill P Pell ◽

Frederick Ho ◽

Carlos Celis-Morales

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Uk Biobank ◽

The Uk ◽

Risk Of Cancer

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Blood pressure and risk of cancer: a Mendelian randomization study

BMC Cancer ◽

10.1186/s12885-021-09067-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Io Ieong Chan ◽

Man Ki Kwok ◽

C. Mary Schooling

Keyword(s):

Blood Pressure ◽

Kidney Cancer ◽

Mendelian Randomization ◽

Sensitivity Analyses ◽

Adult Health ◽

Uk Biobank ◽

Site Specific ◽

Total Cancer ◽

The Uk ◽

Risk Of Cancer

Abstract Background Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers. Methods We applied replicated genetic instruments for systolic and diastolic BP to summary genetic associations with total cancer (37387 cases, 367856 non-cases) from the UK Biobank, and 17 site-specific cancers (663–17881 cases) from a meta-analysis of the UK Biobank and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging. We used inverse-variance weighting with multiplicative random effects as the main analysis, and sensitivity analyses including the weighted median, MR-Egger and multivariable MR adjusted for body mass index and for smoking. For validation, we included breast (Breast Cancer Association Consortium: 133384 cases, 113789 non-cases), prostate (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium: 79194 cases, 61112 non-cases) and lung (International Lung and Cancer Consortium: 10246 cases, 38295 non-cases) cancer from large consortia. We used asthma as a negative control outcome. Results Systolic and diastolic BP were unrelated to total cancer (OR 0.98 per standard deviation higher [95% confidence interval (CI) 0.89, 1.07] and OR 1.00 [95% CI 0.92, 1.08]) and to site-specific cancers after accounting for multiple testing, with consistent findings from consortia. BP was nominally associated with melanoma and possibly kidney cancer, and as expected, not associated with asthma. Sensitivity analyses using other MR methods gave similar results. Conclusions In contrast to previous observational evidence, BP does not appear to be a risk factor for cancer, although an effect on melanoma and kidney cancer cannot be excluded. Other targets for cancer prevention might be more relevant.

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