Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study

Background:

Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS).

Methods:

We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up.

Results:

Among 57 851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506 930 years (SIR, 1.14 (95% confidence interval (CI): 1.03–1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52–0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48–10.75) for colon cancer and 4.81 (95% CI: 2.85–7.60) for rectal cancer. Thereafter, the SIRs declined and 4–10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95.

Conclusion:

We found a decreased risk of colorectal cancer in the period 1–10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.     

Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study

Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulative obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer.     

Parity and risk of thyroid cancer: a nested case-control study of a nationwide Swedish cohort

The association between parity and risk of thyroid cancer was examined in a case-control study nested within a cohort of Swedish women born 1925–60. A total of 1,409 cases of thyroid cancer were compared with 7,019 agematched controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates of relative risk. A weak association was found between parity and risk of thyroid cancer (OR for ever-parous women cf nulliparous was 1.1, CI=1.0–1.3). For the subset of papillary cancers, there was a significantly increased risk (OR for ever-parous cf nulliparous = 1.3, CI=1.0–1.6), and among women diagnosed at the age of 50 or older, there was a positive linear trend with increasing number of livebirths. Women during the first year after a livebirth had an increased risk of thyroid cancer compared with women who delivered 10 or more years before; this association was most prominent among uniparous women (OR=2.5, CI=1.1–5.9). An increased risk was also apparent for age over 20 years at livebirth (among uniparous women) and age over 25 years at last livebirth (among multiparous women). A negligible effect of parity on thyroid cancer risk was seen, but each livebirth may have a short-term and age-dependent promoting effect.Authors are with the Department of Cancer Epidemiology, University Hospital, Uppsala, Sweden (M.R. Galanti, M. Lambe, A. Ebbora, R. Sparda B. Pettersson): Department of Social Medicine, University Hospital, Uppsala, Sweden (M. Lambe); Department of Epidemiology, Harvard School of Public Health, Boston, USA (A. Ekbom). Address correspondence to Dr M. Rosaria Galanti, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This work was supported in part by grant n. 3136-B92-02XBB from the Swedish Cancer Society.     

Association of early life factors and brain tumour risk in a cohort study

Using population-based linked birth and cancer registry data, we investigated whether the risk of brain tumour in childhood (n=155) was associated with perinatal risk factors. This population-based cohort showed that being born into a larger family or to a mother with a history of miscarriage may increase childhood brain tumour risk.     

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.     

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1,348,971) and in 1970 (n=1,377,629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673,443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43,836, 28,702, and 19,670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05-1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer.     

Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden

Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer.Methods: From the Swedish nationwide censuses in 1960 and 1970 we defined three partly overlapping cohorts of women whose occupational titles allowed reproducible classification of physical demands at work in 1960 (n=704,904), in 1970 (n=982,270), or with the same demands in both 1960 and 1970 (n=253,336). The incidence of breast cancer during 1971–89 was ascertained through record linkage to the Swedish Cancer Register. We used Poisson regression to estimate relative risks (RR).Results: A total of 20,419, 22,840, and 8261 breast cancers, respectively, were detected in the three cohorts. In all three cohorts the risk for breast cancer increased monotonically with decreasing level of occupational physical activity and with increasing socioeconomic status. Among women with the same estimated physical activity level in 1960 and 1970 the RR was 1.3 for sedentary as compared with high/very high activity level (95% CI 1.2–1.4; p for trend<0.001). Adjustment for socioeconomic status virtually eliminated this association (RR 1.1; 95% CI 0.9–1.2; p for trend 0.12) leaving a statistically significant 30% gradient only among women aged 50–59 years at follow-up. The association between socioeconomic status and breast cancer risk was largely unchanged after adjustment for occupational physical activity.Conclusion: The protective effect of occupational physical activity on breast cancer risk, if any, appears to be confined to certain age groups.     

Duration of diabetes mellitus and risk of kidney and bladder cancer: a longitudinal nationwide cohort study

Previous studies have suggested that diabetes mellitus (DM) may increase the risk of kidney and bladder cancer; however, little is known about the duration of DM. We aimed to analyze the risk of kidney and bladder cancer according to the duration of DM in a longitudinal nationwide cohort. This study was conducted in a cohort of 9,773,462 participants ≥ 20 years old who underwent a National Health Examination in 2009 and were followed up until December 2017. Cox-proportional hazard models were used to evaluate the risk of kidney and bladder cancer in relation to the duration of DM. During follow-up (mean 7.3 years), kidney and bladder cancer occurred in 11,219 and 13,769 participants, respectively. DM was associated with an increased risk of kidney and bladder cancer (hazard ratio (HR), 95% confidence interval (95% CI); 1.14, 1.09-1.20 and 1.23, 1.17-1.28, respectively). Compared to fasting glucose < 100 mg/dL, impaired fasting glucose (IFG) and longer DM duration were associated with increased risks (HR, 95% CI): IFG (1.05, 1.01-1.10), new-onset DM (1.13, 1.03-1.24), DM < 5 years (1.11, 1.02-1.20), and DM ≥ 5 years (1.25, 1.15-1.36) in kidney cancer; IFG (1.05, 1.01-1.09), new-onset DM (1.10, 1.01-1.19), DM < 5 years (1.26, 1.18-1.35), and DM ≥ 5 years (1.34, 1.26-1.43) in bladder cancer, respectively. Our findings suggest that the subjects with IFG and longer duration of DM had a higher risk for kidney and bladder cancer than those without DM.     

Waist circumference and risk of breast cancer in Korean women: A nationwide cohort study

Although postmenopausal breast cancer (BC) risk has been linked to adiposity, associations between adiposity and premenopausal BC remain unclear. To address this question, we investigated the association of BC risk with measures of adiposity, including body mass index (BMI) and waist circumference (WC), in a large cohort of Asian women. We used a nationwide cohort of adult Korean women selected from the National Health Insurance Corporation database merged with national health examination data from 2009 to 2015. A total of 11,227,948 women were tracked to retrospectively identify incident cases of BC. Our analysis used Cox proportional hazards models to calculate hazard ratios and assess the association of BC risk with BMI and/or WC in both pre‐ and postmenopausal women. BMI and WC were robustly associated with increased risk for postmenopausal BC (p_trend<0.001 for both BMI and WC) but not with premenopausal BC. Association between WC and premenopausal BC was only statistically significant when considering BMI (p_trend=0.044). In contrast, postmenopausal BC was negatively associated with WC when considering BMI (p_trend=0.011). In premenopausal women, WC may predict increased BC risk when considering BMI. However, in postmenopausal women, WC is not superior to BMI as an indicator of BC risk.     

Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study

Background:

There is conflicting evidence regarding bisphosphonates and atrial fibrillation (AF) risk in osteoporosis patients. However, bisphosphonates are used in much higher doses in treatment of bone metastasis and hypercalcemia, but little is known about the AF risk in cancer patients.

Methods:

We conducted a nationwide population-based cohort study using Danish databases. All cancer patients exposed to intravenous bisphosphonates during 2000–2008 were matched with two non-exposed cancer patients by cancer type, distant metastasis presence at diagnosis, age, and gender. We used Cox proportional hazard regression to estimate hazards ratios (HRs) of AF/flutter adjusting for important confounding factors.

Results:

Of the 3981 cancer patients exposed to intravenous bisphosponates, 128 (3.2%) developed AF/flutter. This condition occurred in 192 (2.4%) of the 7906 non-exposed cancer patients, corresponding to an adjusted HR of 1.7 (95% CI: 1.2–2.4).

Conclusion:

Intravenous bisphosphonates may increase AF/flutter risk in cancer patients.     

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970-1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7-4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8-63.2), lip cancer (SIR 53.3; 95% CI 38.0-72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4-8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3-16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.     

Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study

Background:

This study examined the risk of cancer in patients with Hashimoto''s thyroiditis (HT).

Methods:

The Taiwanese National Health Insurance Research Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998–2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer for HT patients was measured using the Cox proportional hazard model.

Results:

The incidence of developing cancer in the HT cohort was 5.07 per 1000 person-years, which was 1.68-fold higher than that in the comparison cohort (P<0.001). Compared with patients aged 20–34 years, patients in older age groups had a higher risk of developing cancer (35–55 years: hazard ratio (HR)=5.96; >55 years: HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer, respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3 years (48.4, 95% confidence interval (CI)=35.0–66.3), with an adjusted HR of 49.4 (95% CI=6.39–382.4).

Conclusion:

Hashimoto''s thyroiditis patients have a higher risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention effort should start soon after HT is diagnosed, while being cautious of colorectal cancer increases with time.     

Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark

Polymyositis and dermatomyositis (PM/DM) have been associated with cancer, although the long-term risks are poorly understood. To evaluate the risk of cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the Danish Central Hospital Discharge Register. Cancer incidence among cohort members was ascertained by linkage to the Danish Cancer Registry using a unique personal-identification number. The overall cancer risk was elevated significantly among patients with DM (standardized incidence ratio [SIR]=3.8, 95 percent confidence interval [CI]=2.6–5.4) and to a lesser extent PM (SIR=1.7, CI=1.1–2.4). Significant excesses were observed for cancers of lung, ovary, and lymphatic and hematopoietic system. However, the excess cancer incidence declined steadily with increasing years since initial diagnosis of PM/DM. The cancer risk was increased about sixfold (SIR=5.9, CI=3.8–8.7) during the first year, but was lower during the second year (SIR=2.5, CI=1.1–4.8), with no significant excesses in subsequent years of follow-up. These findings confirm that PM/DM may occur as a paraneoplastic syndrome that calls for steps aimed at early cancer detection and treatment. Among long-term survivors of PM/DM, however, there is little evidence to warrant extensive preventive and screening measures beyond those recommended for the general population.Drs Chow, McLaughlin, and Fraumeni, and Ms Gridley are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, USA. Dr McLaughlin is currently with the International Epidemiology Institute, Rockville, MD. Ms Mellemkjær and Dr Olsen are with the Division for Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. Address correspondence to Dr Chow, National Cancer Institute 6130 Executive Blvd, EPN/415, Rockville, MD 20852, USA.     

Autoimmune diseases and breast cancer recurrence: a Danish nationwide cohort study

Breast Cancer Research and Treatment - Autoimmune diseases (ADs) comprise a large group of heterogeneous diseases in which the immune system attacks healthy organs. Both intrinsic changes in the...     

Estrogen and risk of gastric cancer: a protective effect in a nationwide cohort study of patients with prostate cancer in Sweden.

BACKGROUND: The global pattern of male predominance in gastric cancer incidence remains unexplained. We tested the hypothesis that estrogen prevents gastric cancer in a cohort of men heavily exposed to estrogen.METHODS: We conducted a nationwide cohort study of men with a diagnosis of prostate cancer recorded in the Swedish Cancer Register in 1961-2000. Because estrogen therapy was the treatment of choice for prostate cancer in Sweden between 1950 and 1980, cohort members diagnosed earlier than 1980 were considered exposed to estrogen. Standardized incidence ratios (SIR) estimated relative risk. Complete follow-up was achieved through cross-linkages within the cancer register and the Swedish nationwide registers of emigration and causes of death.RESULTS: In 515,961 person-years of follow-up, we observed 304 gastric cancers as compared with 349 expected for the cohort members in the predefined "exposed" period 1961-1980, rendering a 13% decreased risk (SIR, 0.87; 95% confidence interval (95% CI), 0.78-0.98). Among patients with a latency of > or =15 years after a prostate cancer diagnosis in 1961-1980, SIR was 0.57 (95% CI, 0.30-0.97), suggesting a dose-response relation. Similarly, reduced risks were found for cardia cancer and noncardia gastric cancer. No decreased risk was found for the cohort members in 1981-2000, when estrogen treatment was less common (SIR, 0.99; 95% CI, 0.89-1.11).CONCLUSIONS: Our study indicates a reduced risk of gastric cancer in a male cohort exposed to estrogen. These results support the hypothesis that estrogen may prevent gastric cancer, but additional studies are warranted.