Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m² increase 0.57, 95% CI 0.50–0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00–1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m²) relative to BMI <25 kg/m² was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80–2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05–1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study—the largest in an Asian country—provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.     

Central adiposity,obesity during early adulthood,and pancreatic cancer mortality in a pooled analysis of cohort studies

BackgroundBody mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk.DesignWe conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18–21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models.ResultsHigher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m²), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m², HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m², HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m², HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m²). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m²).ConclusionsOur results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.     

Body mass index and breast cancer risk in Japan: a pooled analysis of eight population-based cohort studies

BackgroundA positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women.MethodsWe assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models.ResultsAnalytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P < 0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56–1.99), 1.07 (95% CI 0.76–1.52), 0.91 (95% CI 0.64–1.30), 1.15 (95% CI 0.76–1.73), 1.45 (95% CI 0.71–2.94), and 2.25 (95% CI 1.10–4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m². These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up.ConclusionsThe increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women.     

Prospective cohort study of general and central obesity,weight change trajectory and risk of major cancers among Chinese women

General obesity, typically measured using body mass index (BMI), has been associated with an increased risk of several cancers. However, few prospective studies have been conducted in Asian populations. Although central obesity, often measured using waist–hip ratio (WHR), is more predictive for type 2 diabetes and cardiovascular diseases (CVD) risk than BMI, knowledge of its association with cancer incidence is limited. In a cohort of 68,253 eligible Chinese women, we prospectively investigated the association of BMI, WHR and weight change during adulthood with risk of overall cancer and major site‐specific cancers using multivariate Cox proportional hazard models. Compared to the BMI group of 18.5–22.9 kg/m², obese (BMI ≥ 30 kg/m²) women were at an increased risk of developing overall cancer (hazard ratio = 1.36, 95% confidence interval = 1.21–1.52), postmenopausal breast cancer (HR: 2.43, 95% CI: 1.73–3.40), endometrial cancer (HR: 5.34, 95% CI: 3.48–8.18), liver cancer (HR: 1.93, 95% CI: 1.14–3.27) and epithelial ovarian cancer (HR: 2.44, 95% CI: 1.37–4.35). Weight gain during adulthood (per 5 kg gain) was associated with increased risk of all cancers combined (HR: 1.05, 95% CI: 1.03–1.08), postmenopausal breast cancer (HR: 1.17, 95% CI: 1.10–1.24) and endometrial cancer (HR: 1.37, 95% CI: 1.27–1.48). On the other hand, WHR was not associated with cancer risk after adjustment for baseline BMI. These findings suggest that obesity may be associated with cancer risk through different mechanisms from those for type 2 diabetes and CVD and support measures of maintaining health body weight to reduce cancer risk in Chinese women.     

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

BackgroundDespite the lack of scientific data, many cancer patients hold the belief that glucose ‘feeds’ cancer and might affect disease outcome. We aimed to evaluate associations between glucose, hemoglobin A1C (HbA1C), and survival among individuals with diabetes and diabetes associated cancers.MethodsFive retrospective cohort studies were conducted in a large population-representative database. The study population included all patients with diabetes and an incident diagnosis of colorectal, breast, bladder, pancreatic and prostate cancers. Exposure of interest was serum glucose or HbA1C levels within 6 months prior to cancer diagnosis. Cox regression model was used to calculate hazard-ratio (HR) and 95% confidence-interval (CI) for overall survival. Analyses were adjusted for cancer-specific confounders. A subgroup analysis was performed among insulin-treated patients.ResultsStudy cohorts included 7916 individuals with incident cancers and concurrent diabetes. There was no association between HbA1C levels and overall survival in colorectal (HR 1.00, 95% CI 0.95–1.06), breast (HR 1.03, 95% CI 0.95–1.11), bladder (HR 0.94, 95% CI 0.86–1.01), pancreatic (HR 0.98, 95% CI 0.94–1.02), or prostate (HR 1.02, 95% CI 0.96–1.08) cancers. Among diabetes patients treated with insulin, there was increased survival with increasing serum glucose, most prominent for bladder cancer (HR 0.91, 95% CI 0.84–0.99, per 1 mmol/l increase).ConclusionsHigher glucose and HbA1C levels in diabetes patients with incident cancer are not associated with worse overall survival following cancer diagnosis. Among insulin-treated patients, higher glucose levels may be associated with improved survival.     

Associations of early life and adulthood adiposity with risk of epithelial ovarian cancer

BackgroundFew studies have evaluated the association between early life adiposity and ovarian cancer risk. Adiposity during different periods of life may be differentially associated with the risk.Patients and methodsWe prospectively followed 133 526 women in the Nurses' Health Study (NHS; 1980–2012) and NHSII (1989–2013). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ovarian cancer (N = 788) according to validated measures for early life adiposity [body mass index (BMI) at age 10 imputed from somatotype and recalled BMI at age 18) as well as BMI change between age 10 and 18 and after age 18 (current weight assessed on every biennial questionnaire since baseline).ResultsAfter mutual adjustment for BMI at age 10, BMI at age 18 and current BMI, the HR (95% CI) for ovarian cancer risk per 5 kg/m² was 0.84 (0.74–0.96) for BMI at age 10 (P-trend = 0.01), 1.17 (1.03–1.33) for BMI at age 18 (P-trend = 0.02), and 1.06 (0.99–1.14) for current BMI (P-trend = 0.08). However, the inverse association with BMI at age 10 was attenuated after adjusting for BMI change between age 10 and 18 and BMI change after age 18 (HR per 5 kg/m²: 1.04; 95% CI 0.91–1.20; P-trend = 0.55). By contrast, BMI change between age 10 and 18 was strongly positively associated with ovarian cancer risk (HR per 5 kg/m² increase: 1.24; 95% CI 1.11–1.39; P-trend = 0.0002), whereas BMI change since age 18 was only slightly associated with risk (HR per 5 kg/m² increase: 1.06; 95% CI 0.99–1.14; P-trend = 0.10). These associations were in general stronger for premenopausal cases or non-serous tumors.ConclusionEarly life changes in adiposity were more strongly associated with ovarian cancer risk than adulthood changes. The specific mechanisms underlying the associations with adiposity changes during early life warrant further investigation.     

The association between fasting blood glucose trajectory and cancer risk in Chinese population without diabetes

To examine the associations between fasting blood glucose (FBG) trajectories, the changes in FBG over time and the risk of cancer, particularly for gastrointestinal cancer, we enrolled 69,742 participants without diabetes from the Kailuan cohort. FBG trajectories (2006–2010) were modeled by group-based trajectory modeling, and five trajectories were identified: low-increasing (n = 6,275), moderate-stable (n = 44,120), moderate-increasing (n = 10,149), elevated-decreasing (n = 5,244) and elevated-stable (n = 3,954). A total of 1,364 cancer cases were accumulated between 2010 and 2015, including 472 gastrointestinal cancer cases. We used Cox proportional hazards regression models to evaluate the associations between FBG trajectory patterns and the risk of cancer. We further assessed the associations while carefully controlling for initial body mass index (BMI) in 2006 and for changes in BMI during 2006–2010. Relative to the moderate-stable group, we found a higher hazard ratio (HR) for overall cancer in the low-increasing group (HR = 1.26, 95% confidence interval (CI) 1.06–1.50); and for gastrointestinal cancer in the elevated-stable group (HR = 1.66, 95% CI 1.22–2.26). Moreover, among participants with an initial BMI ≥25 kg/m², a positive association with the low-increasing group was observed for both overall cancer and gastrointestinal cancer (HR = 1.54, 95% CI 1.17–2.04; HR = 1.65, 95% CI 1.02–2.66; respectively); among participants with a stable BMI (4.40% loss–5.15% gain), a positive association with the elevated-stable group was observed both for overall cancer and gastrointestinal cancer (HR = 1.43, 95% CI 1.10–1.87; HR = 1.95, 95% CI 1.33–2.86; respectively). Our study observed that FBG trajectories were associated with cancer risk among participants without diabetes, and BMI may modify the associations.     

Cancer incidence in relation to body fatness among 0.5 million men and women: Findings from the China Kadoorie Biobank

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/m² 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.     

The association between metabolic health,obesity phenotype and the risk of breast cancer

Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol‐lowering medication use. During follow‐up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m² with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m² and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR = 1.26, 95% CI: 1.01–1.56), as did women with a BMI ≥25 kg/m² and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR = 1.24, 95% CI: 0.99–1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist‐hip ratio ≥0.85 of 1.58, 95% CI: 1.02–2.46; 1.38, 95% CI: 1.09–1.75; and 1.38, 95% CI: 1.02–1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR = 0.71, 95% CI: 0.52–0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.     

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium

BackgroundThe evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case–control studies from Europe and United States.Subjects and methodsWe harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500 000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking.ResultsA total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI >27.5 kg/m², compared with 22.6–25.0, 1.50; 95% confidence interval (CI) 0.76–2.96]. No association was suggested for tobacco smoking; men drinking >400 g of ethanol per week had an HR of 1.57 (95% CI 0.66–3.70), compared with abstainers.ConclusionsOur study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.     

The association of body fat composition with risk of breast,endometrial, ovarian and colorectal cancers among normal weight participants in the UK Biobank

Background The association between body fat composition and risk of cancer in normal weight individuals (body mass index (BMI) 18.5–24.9 kg/m²) is unclear.Methods We examined the association of measures of adiposity with risk of incident cancers of the breast (postmenopausal), endometrium, ovary and colon/rectum among 149,928 normal weight individuals (40–70 years) who were enrolled in the UK Biobank cohort between 2006 and 2010.Results All of the body fat measures were positively associated with invasive postmenopausal breast cancer risk (hazard ratios (HR) for the uppermost quintile (Q5) versus the lowest quintile (Q1) ranged from 1.32 (95% CI: 1.09–1.60) for waist circumference (WC) to 1.56 (1.28–1.90) for BMI). Trunk fat mass index (HR_{Q5 vs Q1}: 1.72, 95% CI: 1.02–2.89) and WC (HR_{Q5 vs Q1}: 1.65, 95% CI: 1.01–2.70)) were positively associated with risk of endometrial cancer. Among males, trunk fat:trunk fat free mass ratio, trunk fat:leg fat mass ratio and (HR_{Q5 vs Q1}: 1.63, 95% CI: 1.02–2.60; 1.92, 1.20–3.07 and 1.68, 1.05–2.66, respectively) were positively associated with colon cancer risk. None of the body fat measures was associated with risk of ovarian cancer or colorectal cancer in women.Conclusion The findings of this study suggest that the current normal weight category based on BMI includes individuals who are at increased risk of some obesity-related cancers.Subject terms: Cancer, Risk factors     

Coffee consumption and risk of localized,advanced and fatal prostate cancer: a population-based prospective study

BackgroundThe epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited.Materials and methodsA population-based cohort of 44 613 Swedish men aged 45–79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI).ResultsFor localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95–0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95–1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93–1.03)]. We observed evidence of effect modification by BMI for localized PCa (P_interaction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m²) compared with normal-weight men (BMI < 25 kg/m²).ConclusionsWe observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.     

Waist circumference,body mass index,and postmenopausal breast cancer incidence in the Cancer Prevention Study-II Nutrition Cohort

Purpose

High body mass index (BMI) is an established risk factor for postmenopausal breast cancer. However, less is known about associations with waist circumference. In particular, it is unclear whether a larger waist circumference is associated with risk more than would be expected based solely on its contribution to BMI.

Methods

We examined the associations of BMI and waist circumference with risk of postmenopausal breast cancer, with and without mutual adjustment, in the Cancer Prevention Study-II Nutrition Cohort. Analyses included 28,965 postmenopausal women who reported weight and waist circumference on a questionnaire in 1997 and were not taking menopausal hormones.

Results

During a median follow-up of 11.58 years, 1,088 invasive breast cancer cases were identified. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from multivariable-adjusted Cox proportional hazard regression models. Without adjustment for BMI, a larger waist circumference was associated with higher risk of breast cancer (per 10 cm increase in waist circumference, HR = 1.13, 95 % CI 1.08–1.19). However, adjustment for BMI eliminated the association with waist circumference (per 10 cm HR = 1.00, 95 % CI 0.92–1.08). BMI was associated with risk unadjusted for waist circumference (per 1 kg/m² HR = 1.04, 95 % CI 1.03–1.05) and adjusted for waist circumference (per 1 kg/m² HR = 1.04, 95 % CI 1.02–1.06).

Conclusions

Our study of predominantly white women provides evidence that a larger waist circumference is associated with higher risk of postmenopausal breast cancer, but not beyond its contribution to BMI.     

Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies

BackgroundThe International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2–3 drinks/day) alcohol drinking, investigation of the dose–response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region.MethodsTwenty-seven cohort and 34 case–control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose–risk relation.ResultsThe RRs were 1.21 [95% confidence interval (CI) 1.13–1.28] for moderate and 1.52 (95% CI 1.27–1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13–1.37) than for women (RR = 1.08, 95% CI 1.03–1.13; P_{heterogeneity} = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33–2.46; P_{heterogeneity} = 0.04). The dose–risk analysis estimated RRs of 1.07 (95% CI 1.04–1.10), 1.38 (95% CI 1.28–1.50), and 1.82 (95% CI 1.41–2.35) for 10, 50, and 100 g/day of alcohol, respectively.ConclusionsThis meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.     

Association of body mass index in early adulthood and middle age with future site-specific cancer mortality: the Harvard Alumni Health Study

BackgroundThe association between adiposity in early adulthood and subsequent development of specific malignancies is unclear. Further, the potential for mediation by adiposity in middle age has not been well examined. In a rare study, we investigated the association of body mass index (BMI) in early adulthood with mortality from several site-specific cancers.DesignIn the Harvard Alumni Health Study cohort, 19 593 males had a physical examination at the university between 1914 and 1952 (mean age: 18.4 years) and returned a questionnaire in 1962 or 1966 (mean age = 45.1 years). BMI was computed using weight (kg)/height² (m²) at both time points. Vital status follow up continued for a maximum of 82 years.ResultsPositive early adulthood cancer mortality gradients by BMI were found for all malignancies combined (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.05–1.17 for a one standard deviation increase in early adulthood BMI), and for lung (HR = 1.24; 95% CI = 1.10–1.40) and skin (HR = 1.29; 95% CI = 0.96–1.75) cancers. There were also apparent associations for cancers of the oesophagus and urogenital sites. Mediation by BMI in middle age was found to be minimal.ConclusionHigher BMI in early adulthood appears to be a direct risk factor for selected malignancies several decades later.     

Plasma folate concentrations and colorectal cancer risk: A case‐control study nested within the Shanghai Men's Health Study

Previous epidemiological studies of circulating folate concentration and colorectal cancer have reported inconsistent results. We evaluated associations of prediagnostic plasma folate concentration with colorectal cancer risk in a case‐control study nested within the Shanghai Men's Health Study (2002–2010). Included herein are 288 cases who were diagnosed with incident colorectal cancer and 575 controls who were individually matched to cases on baseline characteristics. Folate concentrations in plasma were measured by microbiological assay. Multivariate conditional logistic regression was used to assess associations of plasma folate concentrations with colorectal cancer risk. Plasma folate was nonsignificantly but positively associated with colorectal cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were 1.38 (0.95–2.02) for the middle tertile of plasma folate concentrations and 1.33 (0.90–1.98) for the highest compared to the lowest tertile. The positive association reached statistical significance for the highest tertile of folate concentrations for men with late‐stage colorectal cancer (OR = 2.66; 95% CI = 1.03–6.86) and for the middle tertile for cases diagnosed within the first 4 years after blood collection (OR = 1.72; 95% CI = 1.02–2.92) and for men in the high BMI group (OR = 1.88; 95% CI = 1.14–3.11). In our study population, where folic acid fortification of the food supply and vitamin supplement use are uncommon, plasma folate concentration was positively associated with colorectal cancer risk among men who may have had preneoplastic lesions. These findings need to be confirmed in studies with specific assessment of preneoplastic lesions and repeated measurements of folate level over time.     

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person‐years, 6,711 incident colorectal cancer cases were identified. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82–1.03 in men and pooled HR 0.90, 95% CI 0.76–1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64–0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.     

Body size and obesity during adulthood,and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies

BackgroundTo summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers.MethodWe conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose–response summary relative risks (RRs).ResultsOur findings showed BMI, and BMI in early adulthood (aged 18–21 years) is associated with the risk of Hodgkin’s and non-Hodgkin’s lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m² increase in BMI were 1.12 [95% confidence interval (CI): 1.05–1.20] for HL, 1.05 (95% CI: 1.03–1.08) for NHL, 1.11 (95% CI: 1.05–1.16) for DLBCL, 1.06 (95% CI: 1.03–1.09) for ML, 1.09 (95% CI: 1.03–1.15) for leukaemia, 1.13 (95% CI: 1.04–1.24) for AML, 1.13 (95% CI: 1.05–1.22) for CML and 1.04 (95% CI: 1.00–1.09) for CLL, and were1.12 (95% CI: 1.05–1.19) for NHL, 1.22 (95% CI: 1.09–1.37) for DLBCL, and 1.19 (95% CI: 1.03–1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM.ConclusionOur results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.     

Association of Metformin,Other Antidiabetic Medications,and Statins With Incidence of Colon Cancer in Patients With Type 2 Diabetes

BackgroundMetformin and statins may have anticancer effects, with plausible cellular mechanisms. However, the association of these agents with the risk of colorectal cancer is unclear.Patients and MethodsThis was a retrospective cohort study on a large population (N = 316,317) of patients with type 2 diabetes. Data were obtained from the Diabetes in Finland database (FinDM). In a full cohort analysis, hazard ratios (HRs) with their 95% confidence intervals (CIs) for ever use versus never use were estimated using a multiple Poisson regression model. A nested case–control design within the cohort was used to examine the association of colon cancer (CC) with the defined daily dose of medication. The data were analyzed by conditional logistic regression. The analyses were adjusted for the patient’s age, sex, and duration of diabetes.ResultsIn total, 1351 CC cases were diagnosed during 1996-2011. The results revealed insufficient evidence for an association between metformin (HR, 1.01; 95% CI, 0.90-1.14), other oral antidiabetic medications (HR, 1.05; 95% CI, 0.93-1.19), insulin (HR, 1.02; 95% CI, 0.86-1.22), or statins (HR, 0.94; 95% CI, 0.84-1.05) and the incidence of CC in the full cohort analysis. The results from the case–control study were similar, with no consistent trend in the incidence of CC according to the cumulative dose of metformin or the other studied medications.ConclusionThis study found insufficient evidence for an association between metformin, insulin, other oral type 2 diabetes medications, or statins and the incidence of CC.     

Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC‐Italy study

A carbohydrate‐rich diet, resulting in high blood glucose and insulin, has been hypothesized as involved in colorectal cancer etiology. We investigated dietary glycemic index (GI) and glycemic load (GL), in relation to colorectal cancer, in the prospectively recruited EPIC‐Italy cohort. After a median 11.7 years, 421 colorectal cancers were diagnosed among 47,749 recruited adults. GI and GL were estimated from validated food frequency questionnaires. Multivariable Cox modeling estimated hazard ratios (HRs) for associations between colorectal cancer and intakes of total, high GI and low GI carbohydrate and GI and GL. The adjusted HR of colorectal cancer for highest versus lowest GI quartile was 1.35; 95% confidence interval (CI) 1.03–1.78; p trend 0.031. Increasing high GI carbohydrate intake was also significantly associated with increasing colorectal cancer risk (HR 1.45; 95% CI 1.04–2.03; p trend 0.034), whereas increasing low GI carbohydrate was associated with reducing risk (HR 0.73; 95% CI 0.54–0.98; p trend 0.033). High dietary GI and high GI carbohydrate were associated with increased risks of cancer at all colon sites (HR 1.37; 95% CI 1.00–1.88, HR 1.80; 95% CI 1.22–2.65, respectively), whereas high GI carbohydrate and high GL were associated with increased risk of proximal colon cancer (HR 1.94; 95% CI 1.18–3.16, HR 2.01; 95% CI 1.08–3.74, respectively). After stratification for waist‐to‐hip ratio (WHR), cancer was significantly associated with GI, and high GI carbohydrate, in those with high WHR. These findings suggest that high dietary GI and high carbohydrate intake from high GI foods are associated with increased risk of colorectal cancer.