Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events

Ohkuma, Toshiaki; Peters, Sanne A.E.; Woodward, Mark

doi:10.1007/s00125-018-4664-5

Cited by 151 publications

(122 citation statements)

References 140 publications

(50 reference statements)

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“…In addition, as shown in Fig 2b, Type I diabetes and long-term depression phenotypes were linked to some cancers, suggesting that they were genetic diseases as well. Diabetes and obesity have been shown to be a risk factor for some cancers, for example, a meta-analysis of 121 cohorts including 20 million individuals and one million events confirmed that diabetes is a risk factor for all-site cancer ( 44 ), while obesity can increase cancer incidences of 13 cancer types ( 45 ). A 24-year follow-up study showed that depression increases the risk of cancer ( 46 ), Moreover, a meta-analysis of 16 studies (n=163,000) showed that cancer patients with anxiety and depression had a greater risk of dying from all types of cancer ( 47 ).…”

Section: Resultsmentioning

confidence: 99%

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Xu¹,

Zou

et al. 2018

Preprint

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27Tumor immune microenvironment (TIME) plays an important role in metastasis and 28 immunotherapy. However, it has been not much known how to classify TIMEs and how TIMEs are 29 genetically regulated. Here we showed that tumors were classified into TIME-rich, -intermediate and -30 poor subtypes which had significant differences in clinical outcomes, abundances of tumor-infiltrating 31 lymphocytes (TILs), degree of key immune programs' activation, and immunotherapy response across 32 13 common cancer types (n= ~6,000). Furthermore, TIME-intermediate/-poor patients had significantly 33 more inherited genetic defects (i.e., functional germline variants) in natural killer (NK) cells, antigen 34 processing and presentation (APP) and Wnt signaling pathways than TIME-rich patients, and so did 35 cancer patients than non-cancer individuals (n=4,500). These results suggested that individuals who 36 had more inherited defects in NK cells, APP and Wnt pathways had higher risk of developing 37 cancers. Moreover, in the 13 common cancers the number of inheritably defected genes of NK 38 cells was significantly negative-correlated with patients' survival, TILs' abundance in TIMEs and 39 immunotherapy response, suggesting that inherited defects in NK cells alone were sufficient to shape 40 TILs' recruitment, clinical outcome and immunotherapy response, highlighting that NK cell activation 41 was required in the 13 cancer types to drive the recruitment of immune troops into TIMEs. Thus, we 42proposed that cancer was a disease of NK cell inherited deficiencies. These results had implications in 43 identifying of high-risk individuals based on germline genomes, implementing precision cancer 44 prevention by adoptive transfer of healthy NK cells, and improving existing immunotherapies by 45 combining of adoptive NK cell transfer (i.e., converting TIME-intermediate/-poor tumors into TIME-46 rich tumors) in and anti-PD-1 or CAR-T therapy. 47 48 49

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Section: Resultsmentioning

confidence: 99%

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Xu¹,

Zou

et al. 2018

Preprint

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“…People with diabetes have an increased risk of both pre‐malignant lesions and OSCC, and a modest association between head and neck cancer and diabetes in ‘never‐smokers' . Women with diabetes have a significantly higher relative risk than men of developing oral cancer …”

Section: Discussionmentioning

confidence: 99%

“…28 Women with diabetes have a significantly higher relative risk than men of developing oral cancer. 29 Oral lichenoid lesions have been studied less extensively than OLP in the literature, however, recent studies have recorded MT Abbreviations: OLP, oral lichen planus; OLL, oral lichenoid lesions; OLD, oral lichenoid dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Oral lichenoid dysplasia and not oral lichen planus undergoes malignant transformation at high rates

Shearston

Fateh

Tai

et al. 2019

J Oral Pathology Medicine

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Objectives Oral potentially malignant disorders (OPMD) include a variety of mucosal lesions such as oral lichen planus (OLP), oral lichenoid lesions (OLL) and oral lichenoid dysplasia (OLD). Their rate of malignant transformation ranges from 0% to 34% and is dependent on OPMD type, lesion site and a range of risk factors. This study seeks to determine the proportion of oral lichenoid conditions that transform into oral squamous cell carcinoma (OSCC) in an Australian population. Methods The study is a retrospective audit of patients from a private oral medicine clinic, diagnosed with OLP, OLL or OLD using clinical and histopathological data between 2006 and 2014. Patients were cross‐matched with Cancer Registry data for OSCC, and the rate and time to malignant transformation determined. Results OLP and OLL patients displayed a low risk of malignant transformation; 0.49% (1/206) for OLP and 0% (0/31) for OLL. In contrast, OLD patients, all of whom presented clinically as OLP, were at much higher risk with 6.81% (3/44) developing OSCC over an average time of 4.6 years (±2.4 SD). Rates of smoking and alcohol consumption were no higher in OLD patients compared to others. Conclusions Compared with other oral lichenoid conditions, OLD lesions are at a particularly high risk of malignant transformation and should be managed based on the presence of dysplasia and not the lichenoid inflammatory infiltrate. OLP demonstrates a relatively low rate of malignant transformation. Diagnostic histopathology is important for discriminating OLP from OLD.

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“…[20][21][22][23] In particular, the well-known higher prevalence of smoking, but also the higher prevalence of diabetes in patients with stroke, helps explaining the higher prevalence and was lower and education was shorter in stroke patients; factors also associated with increased risk for cancer. [20][21][22][23] In particular, the well-known higher prevalence of smoking, but also the higher prevalence of diabetes in patients with stroke, helps explaining the higher prevalence and was lower and education was shorter in stroke patients; factors also associated with increased risk for cancer.…”

Section: Risk and Risk Markers Of Occult Cancermentioning

confidence: 99%

“…Risk markers of occult cancer in the stroke population were smoking, male sex, higher age, and diabetes, all factors known to be associated with a higher risk of cancer. [20][21][22][23] In particular, the well-known higher prevalence of smoking, but also the higher prevalence of diabetes in patients with stroke, helps explaining the higher prevalence and was lower and education was shorter in stroke patients; factors also associated with increased risk for cancer. 24 Risk of occult cancer did not differ significantly between ischemic and hemorrhagic strokes meaning that prevalence rates are expected to be the same for ischemic and hemorrhagic strokes.…”

Section: Risk and Risk Markers Of Occult Cancermentioning

confidence: 99%

Prevalence and risk of occult cancer in stroke

2019

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Objectives: Cancer is associated with higher risk of stroke. Whether this translates into higher risk of cancer in stroke of an extent calling for cancer screening in stroke is unclear. We investigated prevalence and risk of occult cancer in stroke compared to the background population without history of stroke. Materials and methods: All patients >40 years of age with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a 1-year follow-up in the stroke and in the background population. Cox regression models were used to study risk in comparison to the background population. Results: Prevalence (per 1000) of occult cancer in the stroke/background cohorts was 25.0/15.8 in women and 29.8/20.4 in men. Prevalence was dependent on age and sex. Highest among stroke patients aged 70-80 years (35.6 in women, 42.4 in men); lowest in patients aged 40-50 years (8.3 in women, 6.8 in men). Stroke was associated with an overall 54% higher risk of occult cancer but risk increased significantly with smoking, hazard ratio (HR) 1.47, age HR 1.27 per 10 years, male sex HR 1.25, and diabetes HR 1.25. Conclusions:Prevalence and risk of occult cancer in stroke is considerable and calls for attention when designing the stroke investigation program. K E Y W O R D Scancer, prevalence, risk, stroke

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Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events

Cited by 151 publications

References 140 publications

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Oral lichenoid dysplasia and not oral lichen planus undergoes malignant transformation at high rates

Prevalence and risk of occult cancer in stroke

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