Reproduction and marriage among male survivors of cancer in childhood,adolescence and young adulthood: a national cohort study

Background:

Increased survival after cancer in young age has made long-term follow-up studies of high external validity important. In this national cohort study, we explored the impact of cancer in young age on reproduction and marital status in male survivors.

Methods:

Hazard ratios (HRs) and relative risks (RRs) of reproductive and marital outcomes were studied for male survivors of cancer in young age (<25 years) and cancer-free male comparisons, born during 1965–1985, by linking compulsory national registries in Norway.

Results:

Male cancer survivors (n=2687) had reduced paternity (HR: 0.72, 95% confidence interval (CI): 0.68–0.76). This was most apparent in survivors of testicular cancer, brain tumours, lymphoma, leukemia and bone tumours, and when diagnosed with cancer before 15 years of age. Male cancer survivors were more likely to avail of assisted reproduction (RR: 3.32, 95% CI: 2.68–4.11). There was no increased risk of perinatal death, congenital malformations, being small for gestational age, of low birth weight or preterm birth in their first offspring. Male cancer survivors were less likely to marry (HR: 0.93, 95% CI: 0.86–1.00), in particular brain tumour survivors.

Conclusions:

In this national cohort study, we demonstrated reduced paternity and increased use of assisted reproduction among male cancer survivors, but no adverse outcome for their first offspring at birth.     

Nut consumption and risk of pancreatic cancer in women

Background:

Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer.

Methods:

We prospectively followed 75 680 women in the Nurses'' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.

Results:

We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables.

Conclusion:

Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.     

Association of tamoxifen use and increased diabetes among Asian women diagnosed with breast cancer

Background:

We conducted a population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes.

Methods:

Data obtained from the Taiwanese National Health Insurance Research Database were used for a population-based cohort study. The study cohort included 22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004. Among them, 15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression analysis.

Results:

Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08–1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19–1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes.

Conclusions:

The results of this population-based cohort study suggested that tamoxifen use in breast cancer patients might increase subsequent diabetes risk. The underlying mechanism remains unclear and further larger studies are mandatory to validate our findings.     

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers

Background:

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations.

Methods:

We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27 037 Finnish male smokers, aged 50–69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models.

Results:

Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73–0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48–0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee.

Conclusion:

These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.     

Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study

Background:

Studies document that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. However, studies on the direct association of magnesium with pancreatic cancer are few and findings are inconclusive. In this study, we aimed to investigate the longitudinal association between magnesium intake and pancreatic cancer incidence in a large prospective cohort study.

Method:

A cohort of 66 806 men and women aged 50–76 years at baseline who participated in the VITamins And Lifestyle (VITAL) study was followed from 2000 to 2008. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatic cancer incidence by magnesium intake categories.

Result:

During an average of 6.8-year follow-up, 151 participants developed pancreatic cancer. Compared with those who met the recommended dietary allowance (RDA) for magnesium intake, the multivariable-adjusted HRs (95% CIs) for pancreatic cancer were 1.42 (0.91, 2.21) for those with magnesium intake in the range of 75–99% RDA and 1.76 (1.04, 2.96) for those with magnesium intake <75% RDA. Every 100 mg per day decrement in magnesium intake was associated with a 24% increase in the incidence of pancreatic cancer (HR: 1.24; 95% CI: 1.02, 1.50; P_trend=0.03). The observed inverse associations appeared not to be appreciably modified by age, gender, body mass index, and non-steroidal anti-inflammatory drug use but appeared to be limited to those taking magnesium supplementation (from multivitamins or individual supplement).

Conclusions:

Findings from this prospective cohort study indicate that magnesium intake may be beneficial in terms of primary prevention of pancreatic cancer.     

Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Background:

Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.

Methods:

During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96–1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.

Conclusion:

Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.     

Insulin-like growth factors and liver cancer risk in male smokers

Background:

The liver is the primary source of circulating insulin-like growth factor (IGF)-I, yet the relation between IGFs and liver cancer is uncertain.

Methods:

In a case–cohort study within a cohort of 29 133 male smokers we examined associations of serum IGF-I and IGF binding protein (IGFBP)-3 with liver cancer (50 cases).

Results:

Nonlinear associations between liver cancer and IGF-I and IGFBP-3 were observed (P=0.04 and P<0.01, respectively), strongest association at lowest levels (odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1–0.7 for 80 vs 30 ng ml⁻¹ of IGF-I; OR=0.2, 95% CI=0.1–0.6 for 1400 vs 700 ng ml⁻¹ of IGFBP-3).

Conclusions:

Low IGF-I and IGFBP-3 levels in male smokers are associated with increased risk of liver cancer.     

Alcohol intake and renal cell cancer risk: a meta-analysis

Background:

An inverse association between alcoholic beverage intake and risk of renal cell cancer has been suggested in recent studies.

Methods:

We examined the association between alcoholic beverages and renal cell cancer risk in a meta-analysis. We identified relevant studies by searching the database of PubMed, EMBASE, and MEDLINE published through August 2011. We combined the study-specific relative risks (RRs) using a random-effects model.

Results:

A total of 20 case–control studies, 3 cohort studies, and 1 pooled analysis of cohort studies were included in the meta-analysis. We observed that alcoholic beverage intake was associated with a lower risk of renal cell cancer in combined analysis of case–control and cohort studies; for total alcoholic beverage intake, combined RRs (95% confidence intervals) comparing top with bottom categories were 0.76 (0.68–0.85) in case–control studies, and 0.71 (0.63–0.78) in cohort studies (P for difference by study design=0.02). The inverse associations were observed for both men and women and for each specific type alcoholic beverage (beer, wine, and liquor). Also, we found that one drink per day of alcoholic beverage conferred the reduction in renal cell cancer risk, but further drinking above that level did not add benefit.

Conclusion:

The findings from our meta-analysis support the hypothesis that alcoholic beverage intake is inversely associated with a lower risk of renal cell cancer, with moderate consumption conferring the protection and higher consumption conferring no additional benefits.     

The association of diabetes with colorectal cancer risk: the Multiethnic Cohort

Background:

Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics.

Methods:

We examined whether this relationship differed by ethnic group, cancer site or tumour stage in a population-based prospective cohort, including 3549 incident colorectal cancer cases identified over a 13-year period (1993–2006) among 199 143 European American, African American, Native Hawaiian, Japanese American and Latino men and women in the Multiethnic Cohort.

Results:

Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics (relative risk (RR)=1.19, 95% confidence interval (CI)=1.09–1.29, P-value (P)<0.001). Positive associations were observed for colon cancer, cancers of both the right and left colon, and cancers diagnosed at a localised and regional/distant stage. The association with colorectal cancer risk was significantly modified by smoking status (P_Interaction=0.0044), with the RR being higher in never smokers (RR=1.32, 95% CI=1.15–1.53, P<0.001) than past (RR=1.19, 95% CI=1.05–1.34, P=0.007) and current smokers (RR=0.90, 95% CI=0.70–1.15, P=0.40).

Conclusion:

These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer.     

A cohort study of the risk of cancer associated with type 2 diabetes

Background:

There is evidence to suggest that diabetes may increase the risk of incidence and mortality from cancer.

Methods:

In a cohort study using record-linkage health-care datasets for Tayside, Scotland in 1993–2004, we followed up 9577 newly diagnosed patients with type 2 diabetes, and two matched non-diabetic comparators, in the national cancer register.

Results and conclusions:

The risk ratio for any cancer, adjusted for deprivation, was 0.99 (95%CI 0.90–1.09). Significantly increased risks were observed for pancreatic, liver and colon cancer.     

Tubal ligation in relation to menopausal symptoms and breast cancer risk

Background:

Local inflammation after tubal ligation may affect ovarian function and breast cancer risk.

Methods:

We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50 884 women).

Results:

Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06–1.12) but not menopausal age (HR 0.99; 95% CI: 0.96–1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85–1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70–1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy.

Conclusion:

Tubal ligation does not influence overall breast cancer risk.     

A prospective investigation of fish,meat and cooking-related carcinogens with endometrial cancer incidence

Background:

There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent.

Methods:

We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77–1.08), white (0.98, 0.83–1.17), processed meats (1.02, 0.86–1.21) and fish (1.10, 95% CI 0.93–1.29). We also found no associations between meat mutagen intakes and endometrial cancer.

Conclusion:

Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.     

Incidence of thyroid cancer in England by ethnic group, 2001–2007

Background:

Thyroid cancer incidence is increasing worldwide, but with large variations in incidence that may reflect either diagnostic bias or true ethnic differences. We sought to determine the effect of ethnicity on the incidence of thyroid cancer in England, a multiethnic population with a single health-care system.

Methods:

We analysed 11 263 thyroid cancer registrations with ethnicity obtained by linkage to the Hospital Episodes Statistics database. Incidence rate ratios (RRs) adjusted for age, sex and income were calculated for the six main non-White ethnic groups in England compared with Whites and to each other.

Results:

Thyroid cancer incidence was higher in all ethnic groups, except Indians, compared with Whites: in Pakistanis (RR 1.79, 99% floating confidence interval (FCI) 1.47–2.19); Bangladeshis (RR 1.99, 99% FCI 1.46–2.71); Black Africans (RR 1.69, 99% FCI 1.34–2.13); Black Caribbeans (RR 1.56, 99% FCI 1.25–1.93); and Chinese (RR 2.14, 99% FCI 1.63–2.80).

Conclusion:

The risk of thyroid cancer in England varies significantly by ethnicity. The elevated incidence in most ethnic minorities is unlikely to be due to diagnostic bias and warrants further investigation.     

The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

Background:

The risk of cancer with hypercalcaemia in primary care is unknown.

Methods:

This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified.

Results:

Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l⁻¹. Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17–3.93, P=<0.001; positive predictive value (PPV) 11.5% females: OR 1.86, 95% CI 1.39–2.50, P<0.001: PPV 4.1%.

Conclusions:

Hypercalcaemia is strongly associated with cancer in primary care, with men at most risk, despite hypercalcaemia being more common in women.     

Intake of coffee,caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer

Background:

Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously.

Methods:

Prospective cohort of 23 356 postmenopausal women with 471 Type I and 71 Type II EC cases.

Results:

Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ⩽1 cup per month: 95% confidence interval (CI): 0.47–0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50–1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m⁻² (RR=0.56; 95% CI: 0.36–0.89).

Conclusion:

Coffee may protect against Type I EC in obese postmenopausal women.     

Vitamin D intake,blood 25(OH)D levels,and breast cancer risk or mortality: a meta-analysis

Background:

Experimental studies suggest potential anti-carcinogenic properties of vitamin D against breast cancer risk, but the epidemiological evidence to date is inconsistent.

Methods:

We searched MEDLINE and EMBASE databases along with a hand search for eligible studies to examine the association between vitamin D status (based on diet and blood 25-hydroxyvitamin D (25(OH)D)) and breast cancer risk or mortality in a meta-analysis. A random-effect model was used to calculate a pooled adjusted relative risk (RR).

Results:

A total of 30 prospective studies (nested case-control or cohort) were included for breast cancer incidence (n=24 studies; 31 867 cases) or mortality (n=6 studies; 870 deaths) among 6092 breast cancer patients. The pooled RRs of breast cancer incidence for the highest vs the lowest vitamin D intake and blood 25(OH)D levels were 0.95 (95% CI: 0.88–1.01) and 0.92 (95% CI: 0.83–1.02), respectively. Among breast cancer patients, high blood 25(OH)D levels were significantly associated with lower breast cancer mortality (pooled RR=0.58, 95% CI: 0.40–0.85) and overall mortality (pooled RR=0.61, 95% CI: 0.48–0.79). There was no evidence of heterogeneity and publication bias.

Conclusions:

Our findings suggest that high vitamin D status is weakly associated with low breast cancer risk but strongly associated with better breast cancer survival.     

Lifestyle factors associated with survival after colorectal cancer diagnosis

Background:

Aside from tumour stage and treatment, little is known about potential factors that may influence survival in colorectal cancer patients. The aim of this study was to investigate the associations between physical activity, obesity and smoking and disease-specific and overall mortality after a colorectal cancer diagnosis.

Methods:

A cohort of 879 colorectal cancer patients, diagnosed in Western Australia between 2005 and 2007, were followed up to 30 June 2012. Cox''s regression models were used to estimate the hazard ratios (HR) for colorectal cancer-specific and overall mortality associated with self-reported pre-diagnosis physical activity, body mass index (BMI) and smoking.

Results:

Significantly lower overall and colorectal cancer-specific mortality was seen in females who reported any level of recent physical activity than in females reporting no activity. The colorectal cancer-specific mortality HR for increasing levels of physical activity in females were 0.34 (95% CI=0.15, 0.75), 0.37 (95% CI=0.17, 0.81) and 0.41 (95% CI=0.18, 0.90). Overweight and obese women had almost twice the risk of dying from any cause or colorectal cancer compared with women of normal weight. Females who were current smokers had worse overall and colorectal cancer-specific mortality than never smokers (overall HR=2.64, 95% CI=1.18, 5.93; colorectal cancer-specific HR=2.70, 95% CI=1.16, 6.29). No significant associations were found in males.

Conclusion:

Physical activity, BMI and smoking may influence survival after a diagnosis of colorectal cancer, with more pronounced results found for females than for males.     

Diabetes and pancreatic cancer survival: a prospective cohort-based study

Background:

Diabetes is a risk factor for pancreatic cancer but its association with survival from pancreatic cancer is poorly understood. Our objective was to investigate the association of diabetes with survival among pancreatic cancer patients in a prospective cohort-based study where diabetes history was ascertained before pancreatic cancer diagnosis.

Methods:

We evaluated survival by baseline (1993–2001) self-reported diabetes history (n=62) among 504 participants that developed exocrine pancreatic cancer within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards model, adjusted for age, sex, body mass index, race, smoking, and tumour stage (local, locally advanced, and metastatic).

Results:

The multivariable-adjusted HR for mortality comparing participants with diabetes to those without was 1.52 (95% CI=1.14–2.04, P-value <0.01). After excluding those diagnosed with pancreatic cancer within 3 years of study enrolment, HR for mortality among those with diabetes was 1.45 (95% CI=1.06–2.00, P-value=0.02).

Conclusions:

Using prospectively collected data, our findings indicate that diabetes is associated with worse survival among patients with pancreatic cancer.     

Diabetes and breast cancer risk: a meta-analysis

Background:

The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research.

Methods:

A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk.

Results:

Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)).

Conclusion:

The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.     

Anthropometric measures and epithelial ovarian cancer risk among Chinese women: results from the Shanghai Women's Health Study

Background:

Studies of anthropometric measures and ovarian cancer risk have predominantly included women of European descent with mixed findings.

Methods:

Data from the prospective Shanghai Women''s Health Study (SWHS) were used to evaluate associations between anthropometric measures and risk of epithelial ovarian cancer (EOC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.

Results:

A total of 152 EOC cases occurred among 70 258 women. Increasing quartiles of weight, hip circumference, and weight gain during adulthood were associated with significantly increased EOC risks. Body mass index (BMI) was also associated; overweight (25⩽BMI<29.99) and obese women (BMI⩾30.0) had significantly increased risks (HR: 1.49, 95% CI: 1.05, 2.13, and HR: 2.42, 95% CI: 1.37, 4.28, respectively). No significant associations were observed for height, waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHER).

Conclusion:

Results from this large prospective study of Chinese women support the hypothesis that general adiposity contributes to the aetiology of ovarian cancer.