There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological ...studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.
During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.
Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.
Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition ...cohort. We included 476,160 individuals mostly aged 35–70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00–1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01–1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03–2.40) compared to those reporting moderate intakes (<6 g/day), but no dose–response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01–1.91) and smokers (1.39; 95% CI 1.01–1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.
What's new?
Findings from the EPIC cohort do not suggest a clear detrimental effect of alcohol on bladder cancer risk. However, we found some association between alcohol and risk of the most aggressive forms of bladder cancer in men and in smokers. Among the different beverages, high intakes of spirits were associated with an increased risk of bladder cancer in men and in smokers, while beer and wine were not. Further studies confirming these results are warranted.
There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We ...evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow‐up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non‐significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 95% CI 0.69, 1.03) and risk of aggressive (HR: 0.88 95% CI 0.61, 1.28) and non‐aggressive tumors (HR: 0.78 95% CI 0.54, 1.14). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.
What's new?
Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire‐based associations between dietary factors and bladder cancer risk.
It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.
We examined the ...associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327,396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.
Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ≤ 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.
This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.
The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol ...consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.
To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.
Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.
Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the ...association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.
Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.
No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).
Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.
Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality ...overall and by subsite in a large Norwegian cohort.
We followed 602,242 participants from four Norwegian health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints.
During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06-1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ(2) =0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ(2) =0.02 and χ(2) =0.04, respectively).
Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively.