C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis.
BMC medicine
BACKGROUND:Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. METHODS:We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. RESULTS:During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P < 0.001 and FDR-adjusted P < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P < 0.050 and FDR-adjusted P > 0.050). In addition, we also observed three different patterns of non-linear associations, including "fast-to-low increase" (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), "increase-to-decrease" (breast cancer), and "decrease-to-platform" (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers. CONCLUSIONS:Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.
10.1186/s12916-022-02506-x
Association between tea consumption and risk of cancer: a prospective cohort study of 0.5 million Chinese adults.
Li Xinyi,Yu Canqing,Guo Yu,Bian Zheng,Shen Zewei,Yang Ling,Chen Yiping,Wei Yongyue,Zhang Hao,Qiu Zhe,Chen Junshi,Chen Feng,Chen Zhengming,Lv Jun,Li Liming,
European journal of epidemiology
Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.
10.1007/s10654-019-00530-5
Cancer incidence in relation to body fatness among 0.5 million men and women: Findings from the China Kadoorie Biobank.
International journal of cancer
High body mass index (BMI) has been associated with an increased risk of several cancers. Evidence relating body fatness, especially based on different anthropometric measures, to risk of major cancers in China from prospective cohort studies is lacking. The prospective China Kadoorie Biobank study recruited 0.5 million adults aged 30-79 years from 10 diverse areas across China during 2004-2008, recording 21,474 incident cancers during 8.95 years of follow-up. BMI, body fat percentage (BFP), waist circumference (WC) and waist-to-hip ratio (WHR) were measured at baseline. We assessed the associations of body fatness with 15 major cancers by calculating Cox regression yielded adjusted hazard ratios (HRs). Each 5 kg/m increase in BMI was associated with an increased risk of endometrial (HR, 2.01; 95% CI, 1.72-2.35), postmenopausal breast (HR, 1.29; 95% CI, 1.18-1.40), colorectal (HR, 1.17; 95% CI, 1.10-1.25) and cervical (HR, 1.15; 95% CI, 1.03-1.29) cancer, whereas it was associated with a reduced risk of esophageal (HR, 0.73; 95% CI, 0.67-0.79), lung (HR, 0.78; 95% CI, 0.74-0.82), liver (HR, 0.85; 95% CI, 0.79-0.92) and gastric (HR, 0.88; 95% CI, 0.82-0.94) cancer. Significant linear trends of BMI-cancer associations were observed, excluding for lung, gastric and cervical cancer (both overall and nonlinear p < 0.05). The relation between BFP, WC and WHR and the above cancers was similar to that of BMI. Our study indicates that either high or low body fatness contributes to the incidence of different types of cancer in China.
10.1002/ijc.32394
Circulating Insulin-Like Growth Factor-1 and Risk of Total and 19 Site-Specific Cancers: Cohort Study Analyses from the UK Biobank.
Qian Frank,Huo Dezheng
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
BACKGROUND:Insulin-like growth factor-1 (IGF-1) has been implicated in several malignancies, but few studies have examined multiple cancers simultaneously. We sought to conduct systematic assessments of the association between IGF-1 and cancer risk. METHODS:We conducted a prospective analysis between IGF-1 and incident total and 19 site-specific cancers among 412,645 individuals enrolled in the UK Biobank with follow-up to 2016. IGF-1 was measured using blood samples provided at the baseline examination. HR and 95% confidence interval (CI) were calculated with multivariable-adjusted Cox models with IGF-1 modeled both in sex-specific quintiles and continuously. RESULTS:Participants were followed for a median of 7.2 years. We observed positive associations between circulating IGF-1 and overall cancer risk for both men (HR = 1.03 per 5-nmol/L increment in IGF-1; 95% CI, 1.01-1.06) and women (HR = 1.03; 95% CI, 1.01-1.06). For specific sites, we observed positive associations for breast (HR = 1.10; 95% CI, 1.07-1.14), prostate (1.09; 95% CI, 1.05-1.12), colorectum (1.07; 95% CI, 1.02-1.11), melanoma (1.08; 95% CI, 1.01-1.15), kidney (1.10; 95% CI, 1.00-1.20), and thyroid (1.22; 95% CI, 1.05-1.42) and inverse associations for lung (0.91; 95% CI, 0.86-0.96), ovaries (0.86; 95% CI, 0.77-0.95), head and neck (0.90; 95% CI, 0.82-0.99), and liver (0.32; 95% CI, 0.26-0.38). The inverse association between IGF-1 and lung cancer was observed only in ever-smokers (HR = 0.88 vs. HR = 1.14; = 0.0005). Analyses comparing extreme quintiles were consistent. CONCLUSIONS:IGF-1 is modestly associated with increased risk of total cancer in both men and women but demonstrated divergent associations for site-specific cancers. IMPACT:Our study suggests that IGF-1 could serve as a target for cancer prevention or treatment.
10.1158/1055-9965.EPI-20-0743
Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study.
PLoS medicine
BACKGROUND:Evidence for the impact of body size and composition on cancer risk is limited. This mendelian randomisation (MR) study investigates evidence supporting causal relationships of body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and height with cancer risk. METHODS AND FINDINGS:Single nucleotide polymorphisms (SNPs) were used as instrumental variables for BMI (312 SNPs), FMI (577 SNPs), FFMI (577 SNPs), and height (293 SNPs). Associations of the genetic variants with 22 site-specific cancers and overall cancer were estimated in 367,561 individuals from the UK Biobank (UKBB) and with lung, breast, ovarian, uterine, and prostate cancer in large international consortia. In the UKBB, genetically predicted BMI was positively associated with overall cancer (odds ratio [OR] per 1 kg/m2 increase 1.01, 95% confidence interval [CI] 1.00-1.02; p = 0.043); several digestive system cancers: stomach (OR 1.13, 95% CI 1.06-1.21; p < 0.001), esophagus (OR 1.10, 95% CI 1.03, 1.17; p = 0.003), liver (OR 1.13, 95% CI 1.03-1.25; p = 0.012), and pancreas (OR 1.06, 95% CI 1.01-1.12; p = 0.016); and lung cancer (OR 1.08, 95% CI 1.04-1.12; p < 0.001). For sex-specific cancers, genetically predicted elevated BMI was associated with an increased risk of uterine cancer (OR 1.10, 95% CI 1.05-1.15; p < 0.001) and with a lower risk of prostate cancer (OR 0.97, 95% CI 0.94-0.99; p = 0.009). When dividing cancers into digestive system versus non-digestive system, genetically predicted BMI was positively associated with digestive system cancers (OR 1.04, 95% CI 1.02-1.06; p < 0.001) but not with non-digestive system cancers (OR 1.01, 95% CI 0.99-1.02; p = 0.369). Genetically predicted FMI was positively associated with liver, pancreatic, and lung cancer and inversely associated with melanoma and prostate cancer. Genetically predicted FFMI was positively associated with non-Hodgkin lymphoma and melanoma. Genetically predicted height was associated with increased risk of overall cancer (OR per 1 standard deviation increase 1.09; 95% CI 1.05-1.12; p < 0.001) and multiple site-specific cancers. Similar results were observed in analyses using the weighted median and MR-Egger methods. Results based on consortium data confirmed the positive associations between BMI and lung and uterine cancer risk as well as the inverse association between BMI and prostate cancer, and, additionally, showed an inverse association between genetically predicted BMI and breast cancer. The main limitations are the assumption that genetic associations with cancer outcomes are mediated via the proposed risk factors and that estimates for some lower frequency cancer types are subject to low precision. CONCLUSIONS:Our results show that the evidence for BMI as a causal risk factor for cancer is mixed. We find that BMI has a consistent causal role in increasing risk of digestive system cancers and a role for sex-specific cancers with inconsistent directions of effect. In contrast, increased height appears to have a consistent risk-increasing effect on overall and site-specific cancers.
10.1371/journal.pmed.1003706
Associations of A Body Shape Index (ABSI) with Cancer Incidence, All-Cause, and at 23 Sites-Findings from the UK Biobank Prospective Cohort Study.
Parra-Soto Solange,Malcomson Fiona C,Ho Frederick K,Pell Jill P,Sharp Linda,Mathers John C,Celis-Morales Carlos
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
BACKGROUND:Few studies have explored the emerging adiposity marker A Body Shape Index (ABSI) with cancer risk. This study investigated the associations between ABSI and the incidence of cancer at 23 sites and all cancer combined. METHODS:Data from 442,610 participants from the UK Biobank prospective study were included in this study. ABSI was used as the exposure. Incidence of cancer at 23 sites was the outcome. Cox proportional hazard models were performed to explore the association of ABSI, and combined ABSI and body mass index (BMI) with cancer risk, after adjusting for multiple testing. RESULTS:36,961 individuals developed cancer during the 8.8 years median follow-up. In multivariable analyses, participants in the highest tertile of ABSI had higher risk of lung [HR, 1.58; 95% confidence interval (CI), 1.44-1.74], liver (HR, 1.45; 95% CI, 1.18-1.77), esophagus (HR, 1.32; 95% CI, 1.12-1.57), colorectal (HR, 1.19; 95% CI, 1.10-1.28), and breast (HR, 1.05; 95% CI, 1.04-1.17) cancers, and all cancers combined (HR, 1.11; 95% CI, 1.08-1.14) compared with the lowest tertile. These associations remained significant after adjustment for BMI. When ABSI was combined with BMI, participants in the highest ABSI who also had a BMI ≥ 25 kg/m were at higher risk of uterus, esophagus, liver, stomach, colorectal, and breast cancers, as well as all cancers combined, compared with those in the lowest ABSI tertile with a normal BMI. CONCLUSIONS:ABSI is associated with an increased risk of five cancers as well as all cancers combined, independently of BMI. IMPACT:ABSI is a useful marker for adiposity. However, cancer risk prediction improves with the combination of BMI.
10.1158/1055-9965.EPI-21-0591
A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort.
Cancer medicine
Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow-up of 7 years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR = 1.14; 95% confidence interval 1.03-1.26 per one standard deviation increment), esophagus (adenocarcinoma, HR = 1.27; 1.12-1.44), gastric cardia (HR = 1.31; 1.07-1.61), colon (HR = 1.18; 1.10-1.26), rectum (HR = 1.13; 1.04-1.22), lung (adenocarcinoma, HR = 1.16; 1.03-1.30; squamous cell carcinoma [SCC], HR = 1.33; 1.17-1.52), and bladder (HR = 1.15; 1.04-1.27), while HI was associated inversely with cancers of the esophagus (adenocarcinoma, HR = 0.89; 0.79-1.00), gastric cardia (HR = 0.79; 0.65-0.96), colon (HR = 0.92; 0.86-0.98), liver (HR = 0.86; 0.75-0.98), and multiple myeloma (HR = 0.86; 0.75-1.00). In women, ABSI was associated positively with cancers of the head and neck (HR = 1.27; 1.10-1.48), esophagus (SCC, HR = 1.37; 1.07-1.76), colon (HR = 1.08; 1.01-1.16), lung (adenocarcinoma, HR = 1.17; 1.06-1.29; SCC, HR = 1.40; 1.20-1.63; small cell, HR = 1.39; 1.14-1.69), kidney (clear-cell, HR = 1.25; 1.03-1.50), and post-menopausal endometrium (HR = 1.11; 1.02-1.20), while HI was associated inversely with skin SCC (HR = 0.91; 0.83-0.99), post-menopausal kidney cancer (HR = 0.77; 0.67-0.88), and post-menopausal melanoma (HR = 0.90; 0.83-0.98). Unusually, ABSI was associated inversely with melanoma in men (HR = 0.89; 0.82-0.96) and pre-menopausal women (HR = 0.77; 0.65-0.91). Waist and hip circumference reflected associations with BMI, when examined individually, and provided biased risk estimates, when combined with BMI. In conclusion, preferential positive associations of ABSI or inverse of HI with several major cancers indicate an important role of factors determining body shape in cancer development.
10.1002/cam4.4097
Diabetes, Glycated Hemoglobin, and Risk of Cancer in the UK Biobank Study.
Peila Rita,Rohan Thomas E
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
BACKGROUND:Evidence suggest that diabetes and glycated hemoglobin (HbA1c) levels are associated with cancer risk. However, previous studies have been limited variably by failure to adjust for cancer-specific risk factors (e.g., body mass index), inattention to diabetes duration and use of antidiabetic medications, and failure to stratify by obesity. METHODS:We examined the association between diabetes, HbA1c, and cancer risk in the UK Biobank, using data from 476,517 participants (54% women), followed for an average period of 7.1 years. Diabetes was defined on the basis of baseline self-reported diagnosis of diabetes and/or use of diabetes medication, while HbA1c measured at baseline was categorized as low (<31 mmol/mol), normal (31-<39 mmol/mol), increased risk (39-<48 mmol/mol), and high risk for diabetes (≥48 mmol/mol). Multivariable Cox proportional hazards models were used to estimate the association of diabetes and cancer at different anatomical sites, with adjustment for cancer-specific risk factors. RESULTS:Diabetes was associated with increased risk of cancers of the stomach, liver, bladder, endometrium, and lung among smokers, and with decreased risk of prostate cancer. Compared with the normal HbA1c category, the increased risk category was positively associated with risk of cancers of the colon, liver, bladder, and lung among smokers, and the high-risk category was associated with increased risk of cancers of the esophagus, liver, pancreas, and bladder, and with decreased risk of prostate cancer. CONCLUSIONS:These results suggest that both diabetes and/or elevated HbA1c are associated with risk of cancer at several anatomic sites. IMPACT:The associations of diabetes and HbA1c levels with cancer suggest their importance in cancer prevention.
10.1158/1055-9965.EPI-19-1623