Diabetes mellitus and breast cancer: a retrospective population-based cohort study

SummaryPurpose Evidence suggests that women with type 2 diabetes may be at increased risk of breast cancer, possibly due to chronic exposure to insulin resistance and/or hyperinsulinemia. The purpose of this study was to compare the incidence of breast cancer in postmenopausal women with and without diabetes.Methods Using population-based validated health databases from Ontario, Canada, this retrospective cohort study compared breast cancer incidence between women, aged 55–79 years, with newly diagnosed diabetes (n=73,796) to women without diabetes (n=391,714).Results Women with diabetes were slightly older, were more likely to reside in a lower income neighborhood, had greater comorbidity, and had more annual physician visits than women without diabetes. After 2.2 million person-years of follow-up from 1994 to 2002, breast cancer incidence was 2.97/1000 person-years in the diabetes group and 2.75/1000 person-years in the non-diabetes group. After adjustment for age and income, there was a significant increase in breast cancer among women with diabetes (hazard ratio, HR, 1.08, 95% confidence interval, CI, 1.01–1.16, p=0.021).Conclusion This study found a small but significant increase in incident breast cancer in a predominantly postmenopausal population of women with diabetes, when compared to women without diabetes. These results support the possibility that insulin resistance or some other aspect of type 2 diabetes may promote breast cancer, and may further direct treatment and prevention strategies.     

Risk of cancer in long-term levothyroxine users: Retrospective population-based study

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.     

Risk of cholecystitis in patients with cancer: a population-based cohort study in Denmark

BACKGROUND.

To the authors' knowledge, little information is available regarding the incidence of cholecystitis among patients with cancer.

METHODS.

The authors conducted a population‐based historical cohort study of 51,228 patients with incident cancer, identified in medical databases of western Denmark between 1995 and 2003. A general population comparison cohort of 512,280 persons was assembled using the Danish Civil Registration System. The occurrence of cholecystitis in the 2 groups was determined by linkage to the regional Hospital Discharge Registry.

RESULTS.

In all, 230 incident diagnoses of cholecystitis were identified in the cancer cohort during 130,185 person‐years (median follow‐up time: 1.6 years), corresponding to an incidence rate of 1.8 of 1000 person‐years. After adjustment for confounders, the relative risk (RR) for cholecystitis among cancer patients compared with the general population cohort was 1.38 (95% confidence interval [95% CI], 1.20‐1.58). Overall, the RR for cholecystitis was doubled during the first 6 months after cancer diagnosis (RR = 1.95; 95% CI, 1.50‐2.54), after which the RR declined but remained greater than 1 throughout the rest of the follow‐up period (RR = 1.23; 95% CI, 1.05‐1.45). Cancer patients between the ages of 51 and 70 years had the highest risk increase for cholecystitis compared with other age groups. During the first 6 months after a cancer diagnosis, pancreatic cancers (12 cholecystitis events; RR = 9.44 [95% CI, 5.18‐17.18]) and colorectal cancers (10 cholecystitis events; RR = 4.98 [95% CI, 2.65‐9.34]) were found to be associated with the greatest cholecystitis risk increase compared with other tumor types. After 6 months, most cancers were associated with a relatively small increased risk, although there was an RR of 4.72 (95% CI, 1.99‐11.21) based on 5 cholecystitis events among thyroid cancer patients.

CONCLUSIONS.

The results of the current study indicate that cholecystitis occurs more frequently among cancer patients than in the general population, particularly within the first 6 months after a cancer diagnosis. Clinicians who treat cancer patients should remain vigilant about this type of infection. Cancer 2008. © 2008 American Cancer Society.     

Alcoholism and cancer risk: a population-based cohort study

The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965–83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4,95 percent confidence interval [CI] = 1.3–1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3–1.6) and among women (SIR = 1.5, CI = 1.1–2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9–5.7), esophagus (SIR = 6.8, CI = 4.5–9.9), larynx (SIR = 3.3, CI = 1.7–6.0), and lung (SIR = 2.1, CI = 1.7–2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9–2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6–1.4), large bowel (SIR = 1.1, CI = 0.8–1.5), prostate (SIR = 1.0, CI = 0.8–1.3), urinary bladder (SIR = 1.0, CI = 0.6–1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3–1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6–2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5–9.1). The results of this study, one of the first to evaluate the incidence of cancer in a population-based cohort of alcoholics of both sexes, are consistent with smaller previous studies, which were usually limited to cancer mortality and of short follow-up.Dr Adami is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Drs McLaughlin and Hsing are with the Biostatistics Branch, National Cancer Institute, Bethesda, MD, USA. Dr Wolk is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Ekbom is with the Department of Surgery and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Persson is with the Department of Obstetrics and Gynaecology and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Address correspondence to Dr Adami, Cancer Epidemiology Unit, University Hospital, S-751 85 Uppsala, Sweden. The work was performed at the Cancer Epidemiology Unit, Uppsala University, Sweden; the research was supported by grants from the Swedish Cancer Society.     

Smoking and alcohol drinking in relation to risk of gastric cancer: a population-based, prospective cohort study

The relations between tobacco, alcohol and risk of gastric cancer need to be established, and any gain from preventive measures should be estimated. We conducted a population-based, prospective cohort study in Nord-Trondelag county in Norway. During 1984-1986, adult residents were invited to a health survey and they answered questionnaires that assessed exposure to tobacco and alcohol, together with potential confounding factors. The exposure assessment regarding alcohol was limited to a 14-day period. New gastric cancers that occurred during follow-up (1984-2002) were identified by linkage to the Norwegian Cancer Registry. Cox proportion hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI), adjusted for sex, education and body mass index. Follow-up of 1,117,648 person-years at risk among 69,962 cohort members revealed 251 gastric cancers, including 224 noncardia cancers. The risk was almost twice as high in daily smokers (HR = 1.88 [CI 95% = 1.33-2.67]) as in never smokers. Independent dose-response relations were found with earlier age at initiation (p = 0.02), frequency (p = 0.00) and duration of smoking (p = 0.00). Attributable risk (AR) of gastric cancer among current smokers was 8.7/100,000 person-years and the corresponding population AR was 18.4%. No statistically significant associations between various degrees of exposure to alcohol and risk of gastric cancer was revealed, but combined high use of cigarettes (>20/day) and alcohol (>5 occasions/14 days) increased the risk of noncardia gastric cancer nearly 5-fold (HR = 4.90 [95% CI = 1.90-12.62]), compared to nonusers. It is concluded that smoking is a dose-dependent risk factor for gastric cancer. Combined high exposure to smoking and alcohol further increases the risk. Successful preventive measures could considerably reduce the incidence of gastric cancer.     

Risk of prostate cancer in low‐dose aspirin users: A retrospective cohort study

A growing body of evidence indicates that use of low‐dose aspirin (LDA) reduces the risk of certain adenocarcinomas. While there are several and consistent findings on the protective effect of LDA on colorectal and other cancers, few and conflicting evidence is available on prostate cancer (PCa). The aim of this study was to assess whether LDA reduces the incidence rate of PCa. We conducted a nationwide, population‐based, retrospective cohort study by using Health Search IMS Health Longitudinal Patient Database (HSD). Patients with ischemic cardio‐ or cerebrovascular disease (index date) were identified. Time‐dependent multivariable Cox proportional hazard models were adopted to estimate Hazard Ratios (HRs) and related 95% confidence intervals (95% CI) of PCa associated with use of LDA. The exposure was lagged by one year to consider the latency of drug effect on the outcome onset. Within a cohort 13,453 patients, the overall incidence rate of PCa was 2.5 per 1,000 person‐years. Use of LDA was associated with a decreased incidence rate of PCa (HR = 0.64; 95% CI: 0.48–0.86), which was primarily driven by a frequency of LDA use equal to or higher than twice per week (HR = 0.60; 95% CI: 0.43–0.83). Such an association was more pronounced (HR = 0.43; 95% CI: 0.21–0.91) when LDA was used for five or more years. Our findings indicate that LDA use might be associated with a reduction of risk of PCa in patients with cardio‐ or cerebrovascular diseases.     

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study

Background:

Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated.

Methods:

A population-based cohort of 41 089 Swedish men aged 45–79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases).

Results:

Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03–1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08–1.53) for localised, 1.05 (95% CI: 0.87–1.25) for advanced, and 1.14 (95% CI: 0.86–1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P_{heterogeneity}=0.27). For localised prostate cancer, RR was 1.55 (1.16–2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers.

Conclusion:

Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.     

Bladder cancer in cancer patients: population-based estimates from a large Swedish study

Background:

This study quantified the risk of urinary bladder neoplasms in cancer patients taking into account the age at first diagnosis, the gender of the patients and the lead time between diagnoses.

Methods:

We used standardised incidence ratios (SIRs) to compare the incidence of bladder tumours in 967 767 cancer patients with the incidence rate in the general Swedish population. A total of 3324 male and 1560 female patients developed bladder tumours at least 1 year after first cancer diagnosis.

Results:

After bladder and renal pelvis cancers, the SIRs of bladder neoplasms were higher in female than in male patients. Men affected by lung, stomach and larynx tumours belonged to the population at high risk for bladder cancer. Treatment of breast, ovarian and cervical cancers seems to contribute to the subsequent development of bladder neoplasms. Long latencies (16–25 years) were observed after testicular, cervical and endometrial cancers. Detection bias had an important role after prostate cancer. Chemotherapy with cyclophosphamide and cisplatin, and also radiotherapy, seem to increase the risk of subsequent neoplasms in the bladder.

Conclusions:

These population-based results may help urologists to assess the risk of bladder neoplasms in cancer survivors. Our data should guide ongoing studies that investigate the effectiveness of bladder cancer screening in cancer patients.     

Diabetes and risk of incident cancer: a large population-based cohort study in Israel

Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately. The main goal of this retrospective cohort study was to evaluate the sex-specific risk of incident overall and site-specific cancer among people with DM compared with those without, who had no reported history of cancer at the start of the follow-up in January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented 1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874 free of DM, respectively. In women, DM was associated with an adjusted hazard ratio of 1.96 (95% CI: 1.53–2.50) and 1.41 (95% CI: 1.20–1.66) for cancers of genital organs and digestive organs, respectively. A significantly reduced HR was observed for skin cancer (0.38; 95% CI: 0.22–0.66). In men with DM, there was no significant increase in overall risk of cancer. DM was related with a 47% reduction in the risk of prostate cancer. These findings suggest that the nature of the association between DM and cancer depends on sex and specific cancer site.     

Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.     

Serum triglyceride concentrations and cancer risk in a large cohort study in Austria

Background:

Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk.

Methods:

Serum triglyceride concentrations were collected in a health investigation (1988–2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI).

Results:

In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47–2.54), rectal (HR, 1.56; 95% CI, 1.00–2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00–3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin''s lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found.

Conclusions:

Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.     

Primary brain tumors following traumatic brain injury--a population-based cohort study in Sweden

Objectives: The aim of this study was to explore the association between traumatic brain injury and brain tumor development. Methods: A cohort of patients hospitalized for traumatic brain injury during 1965–1994 was compiled using the Swedish Inpatient Register. Complete follow-up through 1995 was attained through record linkage with the Swedish Cancer Register, the Cause of Death Register, and the Emigration Register. Standardized incidence ratios (SIRs), defined as the ratios of the observed to the expected numbers of brain tumors, were used as the measure of relative risk. The expected number of brain tumors was calculated by multiplying the observed person-time by age-, gender- and calendar year-specific incidence-rates derived from the general Swedish population. Results: The cohort included 311,006 patients contributing 3,225,317 person-years. A total of 281 cases of brain tumors were diagnosed during follow-up. No associations were found between traumatic brain injury and the risk of primary brain tumors, neither overall (SIR: 1.0; 95% confidence interval (CI): 0.9–1.2), nor in analyses broken down by main groups of brain tumors. Stratified analyses according to age at entry into the cohort, year of follow-up, and severity of the brain injury all showed essentially the same null results. Conclusion: No association between traumatic head injury and primary brain tumors has been found.     

Risk factors for thyroid cancer: a prospective cohort study

Given the higher incidence rate of thyroid cancer among women compared to men and evidence that smoking and alcohol consumption may be inversely related to thyroid cancer risk, we examined thyroid cancer risk in association with menstrual, reproductive and hormonal factors, and cigarette and alcohol consumption, in a prospective cohort study of 89,835 Canadian women aged 40-59 at recruitment who were enrolled in the National Breast Screening Study (NBSS). Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models (using age as the time scale) were used to estimate hazard ratios and 95% confidence intervals for the association between each of the potential risk factors and risk of thyroid cancer overall and by the main histologic subtypes. During a mean of 15.9 years of follow-up, we observed 169 incident thyroid cancer cases. There was no evidence of altered overall thyroid cancer risk with any of the menstrual, reproductive, or hormonal factors. There was evidence of a decreased risk of papillary thyroid cancer among women with 5 or more live births (vs. nulliparous). Age at which smoking commenced, duration of smoking, number of cigarettes smoked per day, pack-years of smoking and alcohol consumption were not associated with altered thyroid cancer risk. The present study provides little support for associations with hormonal factors, smoking, or alcohol consumption, but there is a need for additional prospective data.