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.     

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer,obesity‐linked cancers and breast cancer among women in NHANES III

Although metabolic syndrome (MetS) is a prognostic factor for cancer occurrence, the association of MetS and cancer mortality remains unclear. The purpose of this study was to evaluate whether MetS, components of MetS and C‐reactive protein (CRP) are associated with cancer mortality in women. A total of 400 cancer deaths, with 140 deaths from obesity‐linked‐cancers (OLCas), [breast (BCa), colorectal, pancreatic and endometrial], linked through the National Death Index, were identified from 10,104 eligible subjects aged ≥18 years. Cox proportional hazards regression was used to estimate multivariable‐adjusted hazard ratios (HR) for cancer mortality. MetS was associated with increased deaths for total cancer [HR = 1.33, 95% confidence interval (CI) 1.04–1.70] and BCa [HR = 2.1, 95% CI, 1.09–4.11]. The risk of total cancer [HR = 1.7, 95% CI, 1.12–2.68], OLCas [HR = 2.1, 95% CI, 1.00–4.37] and BCa [HR = 3.8, 95% CI, 1.34–10.91] mortality was highest for women with all MetS components abnormal, compared to those without MetS. Linear associations of blood‐pressure [HR = 2.5, 1.02–6.12, Quartile (Q) 4 vs Q1, p trend = 0.004] and blood‐glucose [HR = 2.2, 1.04–4.60, Q4 vs. Q1, p trend = 0.04] with total‐OLCas mortality were observed. A threefold increased risk of BCa mortality was observed for women with enlarged waist circumference, ≥100.9 cm, [HR = 3.5, 1.14–10.51, p trend = 0.008] and in those with increased blood glucose, ≥101 mg/dL, [HR = 3.2, 1.11–9.20, p trend = 0.03] compared to those in Q1. None of the components of MetS were associated with total‐cancer mortality. CRP was not associated with cancer mortality. In conclusion, MetS is associated with total‐cancer and breast‐cancer mortality, with waist circumference, blood pressure and blood glucose as independent predictors of OLCas and BCa mortality.     

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC)

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend < or = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.     

Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH-AARP Diet and Health Study

Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH-AARP Diet and Health Study who completed a second mailed questionnaire in 1996-1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow-up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: > 102 cm in men and > 88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21-2.63) and women (HR = 1.54, 95% CI: 1.05-2.26). Having both a large waist and BMI in the obese range (≥ 30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18-3.85; HR in women = 1.91, 95% CI: 1.31-3.25) compared to having a normal waist circumference/normal BMI (18.5-24.9 kg/m2). We also observed positive association for weight gain between ages 18-35 in men (gained ≥ 10.0 kg vs. lost/gained < 5 kg, HR = 1.49, 95% CI: 0.93-2.39, p-trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.     

Alcohol consumption and risk of breast cancer by molecular subtype: Prospective analysis of the nurses' health study after 26 years of follow‐up

Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses' Health Study cohort, followed from 1980 to 2006. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6, and epidermal growth factor status from immunostained tumor microarrays in combination with histologic grade. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. We observed suggestive heterogeneity in associations between alcohol and breast cancer by subtype (p_het = 0.06). Alcohol consumers had an increased risk of luminal A breast cancers [n = 1,628 cases, per 10 g/day increment HR (95%CI) = 1.10(1.05–1.15)], and an increased risk that was suggestively stronger for HER2‐type breast cancer [n = 160 cases, HR (95%CI) = 1.16(1.02–1.33)]. We did not observe statistically significant associations between alcohol and risk of luminal B [n = 631 cases, HR (95%CI) = 1.08(0.99–1.16)], basal‐like [n = 254 cases, HR (95%CI) = 0.90(0.77–1.04)], or unclassified [n = 87 cases, HR (95%CI) = 0.90(0.71–1.14)] breast cancer. Alcohol consumption was associated with increased risk of luminal A and HER2‐type breast cancer, but not significantly associated with other subtypes. Given that ERs are expressed in luminal A but not in HER2‐type tumors, our findings suggest that other mechanisms may play a role in the association between alcohol and breast cancer.     

Abdominal adiposity is not a mediator of the protective effect of Mediterranean diet on colorectal cancer

Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e., waist‐to‐hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk. We then estimated the natural indirect effect (NIE, mediated by WHR) and the pure direct effect (PDE, unmediated) of IMI on CRC risk using mediation analyses, considering age, sex, education, physical activity, smoking and EPIC centre as confounders. Increased IMI was associated with significantly decreased odds of high WHR (odds ratio [OR] for an IMI of 6–11 vs. 0–1: 0.88, 95% confidence interval [CI]: 0.81–0.97). There was a positive relationship between WHR and CRC (hazard ratio [HR] for high vs. low WHR: 1.34, 95%CI: 1.09–1.66). The total effect of IMI was protective on CRC risk and was mainly explained by the PDE (HR for an IMI of 6–11 vs. 0–1: 0.51, 95%CI: 0.31–0.83), whereas the NIE was 1.00 (95%CI: 0.94–1.10). In this Mediterranean cohort, the protective effect of the MD on the development of CRC was not mediated by abdominal adiposity. Since this is the first study to investigate the mediating effect of abdominal obesity, other studies are needed to replicate this result.     

Anthropometric factors and ovarian cancer risk: A systematic review and nonlinear dose‐response meta‐analysis of prospective studies

In the World Cancer Research Fund/American Institute for Cancer Research report from 2007 the evidence relating body fatness to ovarian cancer risk was considered inconclusive, while the evidence supported a probably causal relationship between adult attained height and increased risk. Several additional cohort studies have since been published, and therefore we conducted an updated meta‐analysis of the evidence as part of the Continuous Update Project. We searched PubMed and several other databases up to 20th of August 2014. Summary relative risks (RRs) were calculated using a random effects model. The summary relative risk for a 5‐U increment in BMI was 1.07 (95% CI: 1.03–1.11, I² = 54%, n = 28 studies). There was evidence of a nonlinear association, p_nonlinearity < 0.0001, with risk increasing significantly from BMI～28 and above. The summary RR per 5 U increase in BMI in early adulthood was 1.12 (95% CI: 1.05–1.20, I² = 0%, p_{heterogeneity}= 0.54, n = 6), per 5 kg increase in body weight was 1.03 (95% CI: 1.02–1.05, I² = 0%, n = 4) and per 10 cm increase in waist circumference was 1.06 (95% CI: 1.00–1.12, I² = 0%, n = 6). No association was found for weight gain, hip circumference or waist‐to‐hip ratio. The summary RR per 10 cm increase in height was 1.16 (95% CI: 1.11–1.21, I² = 32%, n = 16). In conclusion, greater body fatness as measured by body mass index and weight are positively associated risk of ovarian cancer, and in addition, greater height is associated with increased risk. Further studies are needed to clarify whether abdominal fatness and weight gain is associated with risk.     

Central adiposity in relation to risk of liver cancer in Chinese adults: A prospective study of 0.5 million people

Central adiposity is associated with liver cancer risk beyond general adiposity in Western populations. However, there is little prospective evidence in East Asian populations who are more likely to have central adiposity at given BMI levels. The prospective China Kadoorie Biobank recruited 512,713 adults aged 30–79 years from 10 diverse areas. During 10 years follow-up, 2,847 incident cases of liver cancer were identified. Cox regression was used to estimate adjusted hazard ratios (HR) for liver cancer associated with central adiposity, excluding individuals with cancers and liver diseases at baseline and the first 5 years of follow-up (1,049 incident liver cancer cases). Overall, mean waist circumference (WC) was 82.2 (SD 9.8) cm in men and 79.1 (9.5) cm in women. Central adiposity showed positive associations with liver cancer risk. Associations were strongest for WC and waist-to-hip ratio (WHR), with adjusted HRs per 1-SD of 1.09 (95%CI 1.01–1.18) and 1.12 (1.02–1.23), respectively. The positive associations became stronger when additionally adjusting for BMI (1.26 [1.09–1.46] and 1.14 [1.02–1.28]). The positive association of central obesity (WC ≥90 cm in men and ≥ 80 cm in women) with liver cancer increased progressively with the number of other presenting metabolic risk factors (physical inactivity, diabetes, and hypertension), with HRs of 1.07 (0.90–1.28), 1.17 (1.00–1.38), and 1.91 (1.40–2.59) in those with one, two, and three factors (p for trend 0.006). In this relatively lean Chinese population, there were positive associations of central adiposity with risk of liver cancer, with WHR and WC showing the strongest associations.     

Adult body size,sexual history and adolescent sexual development,may predict risk of developing prostate cancer: Results from the New South Wales Lifestyle and Evaluation of Risk Study (CLEAR)

Prostate cancer (PC) is the most common non‐cutaneous cancer in men worldwide. The relationships between PC and possible risk factors for PC cases (n = 1,181) and male controls (n = 875) from the New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) were examined in this study. The associations between PC risk and paternal history of PC, body mass index (BMI), medical conditions, sexual behaviour, balding pattern and puberty, after adjusting for age, income, region of birth, place of residence, and PSA testing, were examined. Adjusted risk of PC was higher for men with a paternal history of PC (OR = 2.31; 95%CI: 1.70–3.14), personal history of prostatitis (OR = 2.30; 95%CI: 1.44–3.70), benign prostatic hyperplasia (OR = 2.29; 95%CI: 1.79–2.93), being overweight (vs. normal; OR = 1.24; 95%CI: 0.99–1.55) or obese (vs. normal; OR = 1.44; 95%CI: 1.09–1.89), having reported more than seven sexual partners in a lifetime (vs. < 3 partners; OR = 2.00; 95%CI: 1.49–2.68), and having reported more than 5 orgasms a month prior to PC diagnosis (vs. ≤3 orgasms; OR = 1.59; 95%CI: 1.18–2.15). PC risk was lower for men whose timing of puberty was later than their peers (vs. same as peers; OR = 0.75; 95%CI: 0.59–0.97), and a smaller risk reduction of was observed in men whose timing of puberty was earlier than their peers (vs. same as peers; OR = 0.85; 95%CI: 0.61–1.17). No associations were found between PC risk and vertex balding, erectile function, acne, circumcision, vasectomy, asthma or diabetes. These results support a role for adult body size, sexual activity, and adolescent sexual development in PC development.     

Gallstones and incident colorectal cancer in a large pan-European cohort study

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99–1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63–1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.     

Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 incident cases of RCC. Relative risks were calculated using Cox regression, stratified by age and study center and adjusted for smoking status, education, alcohol consumption, physical activity, menopausal status, and hormone replacement therapy use. Among women, an increased risk of RCC was conferred by body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95% confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94-2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p-trend = 0.01); however, waist and hip circumference were no longer significant after controlling for body weight. Among men, hip circumference (RR = 0.44; 95% CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk only after accounting for body weight. Height was not related significantly to RCC risk. Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women, whereas low hip circumference is related to increased RCC risk among men. Our data give further credence to public health efforts aiming to reduce the prevalence of obesity to prevent RCC, in addition to other chronic diseases.     

Prediagnostic body size and breast cancer survival in the E3N cohort study

Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist‐to‐hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer‐specific, and disease‐free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)_{>100vs < 95 cm} = 1.38, 95% Confidence Interval (CI) = 1.02–1.86, P_trend = 0.02) and from breast cancer (HR_{>100vs < 95 cm} = 1.50, CI = 1.03–2.17, P_trend = 0.03), and of second invasive cancer event (HR_{>100vs < 95 cm} = 1.36, CI = 1.11–1.67, P_trend = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference.     

Type 2 diabetes,adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow‐up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause‐specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox‐ and competing risk regression. During follow‐up (mean 17 years), 7,061 incident cancers (3,220 obesity‐related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity‐related cancer incidence and cancer mortality. In T2D subjects, risk of obesity‐related cancer was elevated among men (HR = 1.31, 95% CI: 1.12–1.54; sHR = 1.29, 95% CI: 1.10–1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20–1.49; sHR = 1.30, 95% CI: 1.16–1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83–1.20). There was a significant additive effect of T2D and adiposity on risk of obesity‐related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.     

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16‐ to 19‐year‐old Israeli males. 1,382,093 Jewish Israeli males aged 16–19 who underwent anthropometric measurements, a general intelligence test (GIT) and other examinations during 1967–2011, were followed up to December 31, 2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age‐specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person‐years of follow‐up, 97 were included in multivariable analyses. Compared to “healthy” BMI (18.5–24.9 kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence interval [CI] 1.14–3.55, p = 0.015) in overweight (25.0 ≤ BMI < 30.0 kg/m²) adolescents; and HR = 4.97 (95%CI 2.14–11.53, p = 0.0002) in obese (BMI ≥ 30.0 kg/m²) adolescents. When CDC age‐specific BMI percentiles were assessed results were similar and statistically significant for obesity. In addition, low (vs. high) GIT score (HR = 4.76, 95%CI 1.96–12.50, p = 0.001) and European (vs. west‐Asian) origin (HR = 1.99, 95%CI 1.19–3.34, p = 0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored.     

Baseline serum C‐reactive protein and death from colorectal cancer in the NHANES III cohort

Several prospective studies suggest that C‐reactive protein (CRP), a nonspecific serologic marker of inflammation, might be linked to risk of colorectal cancer (CRC), whereas others have reported null or protective effects. We analyzed data from 7,072 participants (50–85 years) in the U.S. National Health and Nutrition Examination Survey III (1988–1994), a nationally representative cohort (n = 33,994; 2 months–85 years) with vital status follow‐up to 2000. Hazard ratios (HRs) for mortality associated with baseline clinically raised (≥1.00 mg/dL) and intermediate (≥0.22–0.99 mg/dL) CRP levels were estimated using Cox proportional hazards regression controlling for CRC risk factors. There were 59 deaths from CRC, 106 from other obesity‐related cancers (other‐ORCs) and 1,130 from cardiovascular disease (CVD). Participants with clinically raised CRP at baseline were found to have a statistically significant greater risk of CRC death (HRs = 2.36–2.47) in comparison to persons with undetected levels. HRs were lower for death from other‐ORC and CVD (1.82, 95% CI 1.05–3.15; 1.53, 95% CI 1.29–1.81, respectively). Intermediate CRP level was associated with a nonsignificant 10–21% increased risk for CRC death. HR for CRC death was higher among persons with a normal BMI (2.16, 95% 0.96–4.87, p = 0.06) compared to those who were overweight (1.22, 95% CI 0.53–2.78) or obese (1.23, 95% CI, 0.37–4.08). A similar pattern was observed for waist circumference. This effect modification suggests that the impact of chronic inflammation may be independent of excess body fat. Future research is recommended to confirm emerging data that elevated serologic CRP might reflect underlying colonic inflammation.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.     

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.     

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.     

The risk of Barrett's esophagus associated with abdominal obesity in males and females

Esophageal adenocarcinoma arises from Barrett's esophagus (BE). Both occur predominantly in males. The role of abdominal obesity in this sex distribution is uncertain. Our study aimed to determine whether there is an association between abdominal obesity and risk of BE and if present was it modified by sex. A structured interview and anthropometric measures were conducted within a population‐based case–control study. We recruited 237 BE cases (70% male) and 247 population controls, frequency matched by age and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. In the overall group and males, all measures of abdominal obesity [waist circumference (WC), waist–hip ratio (WHR), sagittal abdominal diameter (SAD) and waist–height ratio (WHtR)] were strongly associated with risk of BE (Overall: WC OR 2.2 95% CI 1.4–3.5, WHR 1.8 95% CI 1.2–2.9, SAD 2.3 95% CI 1.4–3.7, WHtR 1.9 95% CI 1.2–3.0, males WC 2.5 95% CI 1.4–4.3, WHR 2.4 95% CI 1.3–4.2, SAD 2.5 95% CI 1.4–4.3, WHtR 1.9 95% CI 1.1–3.4). These associations were minimally attenuated by adjusting for ever‐symptoms of gastroesophageal reflux (GER). These findings suggest in males, non‐GER factors related to abdominal obesity may be important in the development of BE. In females, there was modest association between measures of abdominal obesity and risk of BE but these were all abolished after adjusting for ever‐symptoms of GER. The power to detect differences between sexes in the risk of BE associated with abdominal obesity was limited by the number of females in the study.     

Body fat distribution and risk of premenopausal breast cancer in the Nurses' Health Study II

Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer. We investigated the association between body fat distribution, assessed in 1993 by self-reported waist circumference, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses' Health Study II. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Statistical tests were two-sided. During 426,164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45,799 women. Hormone receptor status information was available for 84% of the breast cancers. The age-standardized incidence rates of breast cancer were 131 per 100,000 person-years among those in the lowest quintile of waist circumference and 136 per 100,000 person-years among those in the highest quintile. No statistically significant associations were found between waist circumference, hip circumference, or the waist to hip ratio and risk of breast cancer. However, each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)-negative breast cancer. The multivariable-adjusted hazard ratios of ER-negative breast cancer for the highest vs the lowest quintile of each body fat distribution measure were 2.75 (95% CI = 1.15 to 6.54; P(trend) = .05) for waist circumference, 2.40 (95% CI = 0.95 to 6.08; P(trend) = .26) for hip circumference, and 1.95 (95% CI = 1.10 to 3.46; P(trend) = .01) for waist to hip ratio. Our findings suggest that body fat distribution does not play an important role in the overall incidence of premenopausal breast cancer but is associated with an increased risk for ER-negative breast cancer.