Mediterranean dietary pattern and cancer risk in the EPIC cohort

Background:

Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.

Methods:

We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0–9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.

Results:

In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95–0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.

Conclusion:

Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.     

A population-based cohort study on sun habits and endometrial cancer

Background:

No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.

Methods:

A population-based cohort study of 29 508 women who answered a questionnaire in 1990–92, of whom 24 098 responded to a follow-up enquiry in 2000–02. They were followed for an average of 15.5 years.

Results:

Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4–0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3–0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5–1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).

Conclusion:

Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.     

A prospective study of lifetime physical activity and prostate cancer incidence and mortality

Background:

The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear.

Methods:

A prospective cohort of 45 887 men aged 45–79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer.

Results:

We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2–27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7–31%). The rate ratio linearly decreased by 7% (95% CI=1–12%) for total, 8% (95% CI=0–16%) for localised and 12% (95% CI=2–20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day.

Conclusions:

Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.     

Second solid cancers after radiotherapy for breast cancer in SEER cancer registries

Background:

Radiotherapy for breast cancer reduces disease recurrence and breast cancer mortality. However, it has also been associated with increased second cancer risks in exposed sites.

Methods:

We evaluated long-term second cancer risks among 182 057 5-year survivors of locoregional invasive breast cancer diagnosed between 1973 and 2000 and reported to US NCI-SEER Program cancer registries. Multivariate Poisson regression was used to estimate the relative risk (RR) and excess cases of second cancer in women who had surgery and radiotherapy, compared with those who had surgery alone. Second cancer sites were grouped according to doses received from typical tangential breast fields.

Results:

By the end of 2005 (median follow-up=13.0 years), 15 498 second solid cancers had occurred, including 6491 contralateral breast cancers. The RRs for radiotherapy were 1.45 (95% confidence interval (CI)=1.33–1.58) for high-dose second cancer sites (1+ Gy: lung, oesophagus, pleura, bone and soft tissue) and 1.09 (1.04–1.15) for contralateral breast cancer (≈1 Gy). These risks decreased with increasing age and year of treatment. There was no evidence of elevated risks for sites receiving medium (0.5–0.99 Gy, RR=0.89 (0.74–1.06)) or low doses (<0.5 Gy, RR=1.01 (0.95–1.07)). The estimated excess cases of cancer in women treated with radiotherapy were as follows: 176 (95% CI=69–284) contralateral breast cancers or 5% (2–8%) of the total in all 1+year survivors, and 292 (222–362) other solid cancers or 6% (4–7%) of the total.

Conclusions:

Most second solid cancers in breast cancer survivors are not related to radiotherapy.     

Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study

Background:

Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear.

Methods:

Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression.

Results:

Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m⁻² increase in BMI, 95% confidence interval (CI): 1.77–1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09–1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77–1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61–2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88–1.22).

Conclusion:

Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women''s current BMI.     

Skin cancer screening participation and impact on melanoma incidence in Germany--an observational study on incidence trends in regions with and without population-based screening

Background:

The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003–June 2004), but not in the German state of Saarland.

Methods:

The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence.

Results:

Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100 000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100 000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: −10.6 per 100 000 (95% CI: −13.3; −7.9); men: −4.1 per 100 000 (95% CI: −6.5; −1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation.

Conclusion:

The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers.     

Leg length, sitting height and postmenopausal breast cancer risk

Background:

Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height.

Methods:

From the prospective Danish cohort ‘Diet, Cancer and Health'', 23 864 postmenopausal women enrolled during 1993–1997 were followed for a diagnosis of breast cancer in the Danish Cancer Registry through 2009.

Results:

The incidence rate ratios for breast cancer were 1.11 (95% CI=1.06–1.16) for each 5 cm increase in total height and 1.09 (95% CI=1.01–1.17) and 1.14 (95% CI=1.04–1.25) for each 5 cm increase in leg length and sitting height, respectively. There was no statistical significant difference between the associations for leg length and sitting height (P=0.47).

Conclusion:

Leg length does not seem to be more strongly associated with breast cancer among postmenopausal women than sitting height.     

Antenatal maternal bereavement and childhood cancer in the offspring: a population-based cohort study in 6 million children

Background:

Prenatal stress may increase the susceptibility to childhood cancer by affecting immune responses and hormonal balance. We examined whether antenatal stress following maternal bereavement increased the risk of childhood cancer.

Methods:

All children born in Denmark from 1968 to 2007 (N=2 743 560) and in Sweden from 1973 to 2006 (N=3 400 212) were included in this study. We compared cancer risks in children born to women who lost a first-degree relative (a child, spouse, a parent, or a sibling) the year before pregnancy or during pregnancy with cancer risks in children of women who did not experience such bereavement.

Results:

A total of 9795 childhood cancer cases were observed during follow-up of 68 360 707 person years. Children born to women who lost a child or a spouse, but not those who lost other relatives, had an average 30% increased risk of any cancer (hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.96–1.77). The HRs were the highest for non-Hodgkin disease (512 cases in total, HR 3.40, 95% CI 1.51–7.65), hepatic cancer (125 cases in total, HR 5.51, 95% CI 1.34–22.64), and testicular cancer (86 cases in total, HR 8.52, 95% CI 2.03–37.73).

Conclusion:

Our data suggest that severe antenatal stress following maternal bereavement, especially due to loss of a child or a spouse, is associated with an increased risk of certain childhood cancers in the offspring, such as hepatic cancer and non-Hodgkin disease, but not with childhood cancer in general.     

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996

Background:

Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected.

Methods:

Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate.

Results:

Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57–62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55–8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52–12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40–9.33) in 1969–1973 to 34.71 (95% CI: 23.10–52.16) in 1992–1996 for those with cirrhosis compared with those without.

Conclusion:

In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.     

Hand pattern indicates prostate cancer risk

Background:

The ratio of digit lengths is fixed in utero, and may be a proxy indicator for prenatal testosterone levels.

Methods:

We analysed the right-hand pattern and prostate cancer risk in 1524 prostate cancer cases and 3044 population-based controls.

Results:

Compared with index finger shorter than ring finger (low 2D : 4D), men with index finger longer than ring finger (high 2D : 4D) showed a negative association, suggesting a protective effect with a 33% risk reduction (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.57–0.80). Risk reduction was even greater (87%) in age group <60 (OR 0.13, 95% CI 0.09–0.21).

Conclusion:

Pattern of finger lengths may be a simple marker of prostate cancer risk, with length of 2D greater than 4D suggestive of lower risk.     

Effects of annual vs triennial mammography interval on breast cancer incidence and mortality in ages 40-49 in Finland

Background:

The aim of this study was to evaluate the effects of mammography screening invitation interval on breast cancer mortality in women aged 40–49 years.

Methods:

Since 1987 in Turku, Finland, women aged 40–49 years and born in even calendar years were invited for mammography screening annually and those born in odd years triennially. The female cohorts born during 1945–1955 were followed for up to 10 years for incident breast cancers and thereafter for an additional 3 years for mortality.

Results:

Among 14 765 women free of breast cancer at age 40, there were 207 incident primary invasive breast cancers diagnosed before the age of 50. Of these, 36 women died of breast cancer. The mean follow-up time for cancer incidence was 9.8 years and for mortality 12.8 years. The incidence of breast cancer was similar in the annual and triennial invitation groups (RR: 0.98, 95% confidence interval (CI): 0.75–1.29). Further, there were no significant differences in overall mortality (RR: 1.20, 95% CI: 0.99–1.46) or in incidence-based breast cancer mortality (RR: 1.14, 95% CI: 0.59–1.27) between the annual and triennial invitation groups.

Conclusions:

There were no differences in the incidence of breast cancer or incidence-based breast cancer mortality between the women who were invited for screening annually or triennially.     

Incidence trends of vestibular schwannomas in Denmark, Finland, Norway and Sweden in 1987-2007

Background:

The reported incidence rates of vestibular schwannomas (VS) vary substantially, but it is unclear as to what extent the variation reflects differences in risk or recording practices. Our aim was to describe the incidence rates of VS in Denmark, Finland, Norway and Sweden between 1987 and 2007.

Methods:

Comprehensive data were available from all registries only for the period from 1987 to 2007. An analysis of a longer time period (1965–2007) was conducted with the Norwegian and Swedish data.

Results:

The average age-standardised incidence rates during 1987–2007 varied from 6.1 per 1 000 000 person-years (95% confidence interval (CI), 5.4–6.7) among Finnish men to 11.6 (95% CI, 10.4–12.7) in Danish men, and from 6.4 per 1 000 000 person-years (95% CI, 5.7–7.0) among Swedish women to 11.6 (95% CI, 10.5–12.8) among Danish women. An overall annual increase of 3.0% (95% CI 2.1–3.9) was observed when all countries and both sexes were combined, with considerable differences between countries. However, the practices of both reporting and coding VS cases varied markedly between countries and over time, which poses a challenge for interpretation of the results.

Conclusion:

The overall incidence of VS increased in all the four Nordic countries combined between 1987 and 2007, with marked differences between countries. However, the incidence rates more or less stabilised in the late 1990s, showing relatively constant incidence rates and even some decline after 2000.     

Exposure to cyclooxygenase-2 inhibitors and risk of cancer: nested case-control studies

Background:

Selective cyclooxygenase-2 (COX2) inhibitors are widely used as analgesics and it is unclear whether its long-term use affects cancer risk.

Methods:

A series of nested case–control studies using the QResearch primary care database. Associations of COX2 inhibitor use with risk of all cancers and 10 common site-specific cancers were estimated using conditional logistic regression adjusted for comorbidities, smoking status, socioeconomic status, and use of non-steroidal anti-inflammatory drugs, aspirin and statins.

Results:

A total of 88 125 cancers, diagnosed between 1998 and 2008, matched with up to five controls, were analysed. Use of COX2 inhibitors for more than a year was associated with a significantly increased risk of breast cancer (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.08–1.42) and haematological malignancies (OR 1.38, 95% CI 1.12–1.69) and a decreased risk of colorectal cancer (OR 0.76, 95% CI 0.63–0.92). There were no other significant associations.

Conclusion:

Prolonged use of COX2 inhibitors was associated with an increased risk of breast and haematological cancers and decreased risk of colorectal cancer. These findings need to be confirmed using other data sources.     

The impact of BMI on subgroups of uterine cancer

Background:

Obesity increases the risk of uterine cancer, but results by histological type have differed.

Methods:

We followed 36 755 women for 17.8 years for uterine cancers.

Results and conclusion:

Body mass index (BMI) was positively associated with uterine cancers as a whole, particularly for endometrioid adenocarcinomas, for which the relative risk for very obese women (BMI: ⩾40 kg m⁻²) compared with lean (BMI: 20–24 kg m⁻²) women, was 11.1 (95% confidence interval: 5.2–23.8).     

Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies

Background:

Whether red and processed meat consumption is a risk factor for pancreatic cancer remains unclear. We conducted a meta-analysis to summarise the evidence from prospective studies of red and processed meat consumption and pancreatic cancer risk.

Methods:

Relevant studies were identified by searching PubMed and EMBASE databases through November 2011. Study-specific results were pooled using a random-effects model.

Results:

Eleven prospective studies, with 6643 pancreatic cancer cases, were included in the meta-analysis. An increase in red meat consumption of 120 g per day was associated with an overall relative risk (RR) of 1.13 (95% confidence interval (CI)=0.93–1.39; P_{heterogeneity}<0.001). Red meat consumption was positively associated with pancreatic cancer risk in men (RR=1.29; 95% CI=1.08–1.53; P_{heterogeneity}=0.28; five studies), but not in women (RR=0.93; 95% CI=0.74–1.16; P_{heterogeneity}=0.21; six studies). The RR of pancreatic cancer for a 50 g per day increase in processed meat consumption was 1.19 (95% CI=1.04–1.36; P_{heterogeneity}=0.46).

Conclusion:

Findings from this meta-analysis indicate that processed meat consumption is positively associated with pancreatic cancer risk. Red meat consumption was associated with an increased risk of pancreatic cancer in men. Further prospective studies are needed to confirm these findings.     

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Background:

The relationship between prostate cancer and height is uncertain.

Methods:

We prospectively examined the association of height with prostate cancer among 34268 men in the prostate, lung, colorectal, and ovarian cancer trial. Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up.

Results:

Overall, tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease, but the risk for aggressive prostate cancer tended to be greater in taller men (Gleason score ⩾7 or stage ⩾III; P trend=0.05; relative risk (RR) for 190 cm+ vs ⩽170 cm=1.39, 95% confidence interval (95% CI): 0.96–2.01). This association was largely limited to men below the age of 65 years (P trend=0.008; RR for 190 cm+ vs ⩽170 cm=1.76, 95% CI: 1.06–2.93; P for interaction=0.009), although the number of cases was small and risk estimates were somewhat unstable.

Conclusion:

The results of this large prospective prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis

Background:

An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women''s cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population.

Methods:

Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies.

Results:

The five studies included 47 325 SLE patients (42 171 females) observed for 282 553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.

Conclusions:

Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.