Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.     

Comparison of anthropometric measurements of adiposity in relation to cancer risk: a systematic review of prospective studies

Purpose

In epidemiology, the relationship between increased adiposity and cancer risk has long been recognized. However, whether the association is the same for measures of abdominal or whole body adiposity is unclear. The aim of this systematic review is to compare cancer risk, associated with body mass index (BMI), an indicator of whole body adiposity, with indicators of abdominal adiposity in studies in which these indicators have been directly measured.

Methods

We conducted a systematic search from 1974 (EMBASE) and 1988 (PubMed) to September 2015 with keywords related to adiposity and cancer. Included studies were limited to cohort studies reporting directly measured anthropometry and performing mutually adjusted analyses.

Results

Thirteen articles were identified, with two reporting on breast cancer, three on colorectal cancer, three on endometrial cancer, two on gastro-oesophageal cancer, two on renal cancer, one on ovarian cancer, one on bladder cancer, one on liver and biliary tract cancer and one on leukaemia. Evidence suggests that abdominal adiposity is a stronger predictor than whole body adiposity for gastro-oesophageal, leukaemia and liver and biliary tract cancer in men and women and for renal cancer in women. Abdominal adiposity was a stronger predictor for bladder and colorectal cancer in women, while only BMI was a predictor in men. In contrast, BMI appears to be a stronger predictor for ovarian cancer. For breast and endometrial cancer, both measures were predictors for cancer risk in postmenopausal women.

Conclusions

Only few studies used mutually adjusted and measured anthropometric indicators when studying adiposity–cancer associations. Further research investigating cancer risk and adiposity should include more accurate non-invasive indicators of body fat deposition and focus on the understudied cancer types, namely leukaemia, ovarian, bladder and liver and biliary tract cancer.

     

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort

Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.     

Prospective investigation of poultry and fish intake in relation to cancer risk

Dietary guidelines advise consumers to limit intake of red meat and choose lean protein sources, such as poultry and fish. Poultry consumption has been steadily increasing in the United States, but the effect on cancer risk remains unclear. In a large U.S. cohort, we prospectively investigated poultry and fish intake and cancer risk across a range of malignancies in men and women. Diet was assessed at baseline (1995-1996) with a food frequency questionnaire in 492,186 participants of the NIH-AARP Diet and Health Study. Over a mean follow-up of 9 years, we identified 74,418 incident cancer cases. In multivariable Cox proportional hazards regression models, we estimated the substitution and addition effects of white meat (poultry and fish) intake in relation to cancer risk. In substitution models with total meat intake held constant, a 10-g (per 1,000 kcal) increase in white meat intake offset by an equal decrease in red meat intake was associated with a statistically significant reduced (3%-20%) risk of cancers of the esophagus, liver, colon, rectum, anus, lung, and pleura. In addition models with red meat intake held constant, poultry intake remained inversely associated with esophageal squamous cell carcinoma, liver cancer, and lung cancer, but we observed mixed findings for fish intake. As the dietary recommendations intend, the inverse association observed between white meat intake and cancer risk may be largely due to the substitution of red meat. Simply increasing fish or poultry intake, without reducing red meat intake, may be less beneficial for cancer prevention.     

Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study

Introduction

Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies.

Methods

Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure.

Results

Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013).

Conclusion

There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power.     

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background:

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.

Methods:

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.

Results:

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 (HR_Q5–Q1) 0.74, 95% confidence interval (CI): 0.61–0.91; P-trend=0.009) and lignans (HR_Q5–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.

Conclusions:

Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.     

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre‐diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord‐Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow‐up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D₂ and 25(OH)D₃ combined] concentrations were determined using isotope‐dilution liquid chromatography‐tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre‐defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season‐standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre‐diagnostic concentrations of vitamin D, they are not statistically significant.     

Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia.

Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each associated with an increased risk of gastric cancer (GC). To explore further the influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95% confidence intervals of developing GC were calculated for each risk factor using multiple logistic regression analysis. ORs for H. pylori infection and IM were 2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II and 39.75 (14.34-110.2) for type III. Stratification analysis by histological subtype and stage of GC showed a particularly high OR for IM in intestinal type (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both H. pylori and IM are related to GC risk. Type III IM is a more specific marker of premalignancy, with relevance, in particular, to the early and intestinal type of GC.     

Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy)

Objective: Insulin resistance and increased levels of serum steroids have been hypothesized to be relevant etiological factors for breast cancer. Measurements of markers of insulin resistance and elevated serum steroids may identify women at high risk for breast cancer. The present study analyzed the association of breast cancer with markers of insulin resistance and elevated serum sex steroids, abdominal adiposity, increase in sebum production and hirsutism in a case–control study nested in a prospective cohort study. Methods: Between 1987 and 1992, 10,786 women (aged 35–69) were recruited in a prospective study on breast cancer in Italy, the ORDET study. Women with a history of cancer and on hormone therapy were excluded at baseline. At recruitment, abdominal adiposity was calculated from the ratio of waist-to-hip circumferences. Sebum production was measured on the forehead under standardized conditions using a sebumeter. Nine androgen-sensitive body areas were evaluated for hirsutism and a total hirsutism score was computed. After an average of 5.5 years of follow-up, 144 breast cancer cases were identified among the participants of the cohort. For each breast cancer case, four matched controls were randomly chosen from members of the cohort who did not develop breast cancer during the follow-up period. Results: Waist-to-hip ratio was associated with breast cancer in premenopausal women: age and body mass index (BMI) adjusted relative risk (RR) for the highest tertile of waist-to-hip ratio was 2.2 [95% confidence interval (CI) 1.04–4.75], p for trend 0.03. In the analysis conducted within strata of BMI, the effect of waist-to-hip ratio was confined to the group of thinner women: RR for the highest tertile of waist-to-hip ratio was 3.4 (95% CI 1.2–9.5). Sebum production and hirsutism were associated with breast cancer among postmenopausal women. Age and BMI adjusted RRs for the upper tertiles were 2.2 (95% CI 1.1–4.6), p for trend 0.01, and 2.3 (95% CI 1.1–4.9), p for trend 0.03, for sebum and hirsutism, respectively. Conclusion: These results add evidence for a role of hormones and metabolic alterations in breast cancer etiology and for different relations of these risk factors with breast cancer in premenopausal and postmenopausal women.     

Early life risk factors in cancer: the relation of birth weight to adult obesity

The intrauterine environment appears to play a role in the development of adult diseases, including several prominent cancers. Our study aims to characterize the relationship between birth weight, a measure of the intrauterine environment, and adult obesity. A population-based sample of women aged 50-79, living in the states of Massachusetts, New Hampshire or Wisconsin, were randomly selected from lists of licensed drivers and Medicare beneficiaries to participate as controls in a case-control study of breast cancer. Information on birth weight, adult height and adult weight were collected through structured telephone interviews from 1992-1995. Our analysis was based on 1,850 interviews. A U-shaped relationship between birth weight and adult BMI was observed. Median adult BMI for the birth weight categories (in kilograms) <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9, 3.9<4.5 and > or =4.5 were 26.6, 24.4, 25.1, 25.5, 25.4 and 26.6 kg/m respectively. Compared to women 2.5<3.2 kg at birth, women in highest birth weight category (> or =4.5 kg) had an odds ratio of 1.99 (95% CI 1.13-3.48) of being obese (> or =30 kg/m(2)) as adults. The odds ratio for women in the <2.3 kg birth weight category was 1.67 (95% CI 1.01-2.76). These data suggest that both low and high birth weights are associated with higher adult BMI and support the hypothesis that fetal experience may influence adult obesity with potential consequences for risk of several major cancers.     

Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality

Background:

Aims of this study were to describe the prevalence of comorbidity in newly diagnosed elderly cancer cases compared with the background population and to describe its influence on overall and cancer mortality.

Methods:

Population-based study of all 70+ year-olds in a Danish province diagnosed with breast, lung, colorectal, prostate, or ovarian cancer from 1 January 1996 to 31 December 2006. Comorbidity was measured according to Charlson''s comorbidity index (CCI). Prevalence of comorbidity in newly diagnosed cancer patients was compared with a control group by conditional logistic regression, and influence of comorbidity on mortality was analysed by Cox proportional hazards method.

Results:

A total of 6325 incident cancer cases were identified. Elderly lung and colorectal cancer patients had significantly more comorbidity than the background population. Severe comorbidity was associated with higher overall mortality in the lung, colorectal, and prostate cancer patients, hazard ratios 1.51 (95% CI 1.24–1.83), 1.41 (95% CI 1.14–1.73), and 2.14 (95% CI 1.65–2.77), respectively. Comorbidity did not affect cancer-specific mortality in general.

Conclusion:

Colorectal and lung cancer was associated with increased comorbidity burden in the elderly compared with the background population. Comorbidity was associated with increased overall mortality in elderly cancer patients but not consistently with cancer-specific mortality.     

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.     

Plasma methionine,choline, betaine,and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

BackgroundDisturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low.Patients and methodsWe conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations.ResultsOverall, methionine (OR: 0.79, 95% CI: 0.63–0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60–0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66–1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50–1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43–0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk.ConclusionsIndividuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.     

Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14–1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11–1.65), 1.26 (95% CI: 1.00–1.60), and 1.40 (95% CI: 1.01–1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04–2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78–2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13–1.53) (p_interaction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.     

Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: Prospective analysis in the Generations Study

Preeclampsia and hyperemesis gravidarum are pregnancy complications associated with altered sex hormone levels. Previous studies suggest preeclampsia may be associated with a decreased risk of subsequent breast cancer and hyperemesis with an increased risk, but the evidence remains unclear. We used data from the Generations Study, a large prospective study of women in the United Kingdom, to estimate relative risks of breast cancer in relation to a history of preeclampsia and hyperemesis using Cox regression adjusting for known breast cancer risk factors. During 7.5 years average follow‐up of 82,053 parous women, 1,969 were diagnosed with invasive or in situ breast cancer. Women who had experienced preeclampsia during pregnancy had a significantly decreased risk of premenopausal breast cancer (hazard ratio (HR) =0.67, 95% confidence interval (CI): 0.49–0.90) and of HER2‐enriched tumours (HR = 0.33, 95% CI: 0.12–0.91), but there was no association with overall (HR = 0.90, 95% CI: 0.80–1.02) or postmenopausal (HR = 0.97, 95% CI: 0.85–1.12) breast cancer risk. Risk reductions among premenopausal women were strongest within 20 years since the last pregnancy with preeclampsia. Hyperemesis was associated with a significantly increased risk of HER2‐enriched tumours (HR = 1.76, 95% CI: 1.07–2.87), but not with other intrinsic subtypes or breast cancer risk overall. These results provide evidence that preeclampsia is associated with a decreased risk of premenopausal and HER2‐enriched breast cancer and that hyperemesis, although not associated with breast cancer risk overall, may be associated with raised risk of HER2‐enriched tumours.     

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported.

Methods:

During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145 112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer.

Results:

Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83–0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11–2.93; RR=1.38, 95% CI: 1.01–1.87, respectively).

Conclusion:

The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.     

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06-1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (P(trend)=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.