Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.     

Angiosarcoma after radiotherapy: a cohort study of 332,163 Finnish cancer patients

We evaluated the risk of angiosarcoma after radiotherapy among all patients with cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, or rectum, and lymphoma diagnosed in Finland during 1953-2003, identified from the Finnish Cancer Registry. Only angiosarcomas of the trunk were considered, this being the target of radiotherapy for the first cancer. In the follow-up of 1.8 million person-years at risk, 19 angiosarcomas developed, all after breast and gynaecological cancer. Excess of angiosarcomas over national incidence rates were observed after radiotherapy without chemotherapy (standardised incidence ratio (SIR) 6.0, 95% confidence interval (CI) 2.7-11), after both radiotherapy and chemotherapy (SIR 100, 95% CI 12-360), and after other treatments (SIR 3.6, 95% CI 1.6-7.1). In the regression analysis however, the adjusted rate ratio for radiotherapy was 1.0 (95% CI 0.23-4.4). Although an increased risk of angiosarcoma among cancer patients is evident, especially with breast and gynaecological cancer, the excess does not appear to be strongly related to radiotherapy.     

Familial risk of colon and rectal cancer in Iceland: Evidence for different etiologic factors?

The aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs.     

Risk of prostate, breast and colorectal cancer after skin cancer diagnosis

Ultraviolet radiation is the major cause of skin cancer, but promotes vitamin D synthesis, and vitamin D has been inversely related to the risk of several common cancers including prostate, breast and colorectum. We therefore computed the incidence of prostate, breast and colorectal cancer following skin cancer using the datasets of the Swiss cancer Registries of Vaud and Neuchatel. Between 1974 and 2005, 6,985 histologically confirmed squamous cell skin cancers, 21,046 basal cell carcinomas and 3,346 cutaneous malignant melanomas were registered, and followed up to the end of 2005 for the occurrence of second primary cancer of the prostate, breast and colorectum. Overall, 680 prostate cancers were observed versus 568.3 expected (standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI): 1.11-1.29), 440 breast cancers were observed versus 371.5 expected (SIR = 1.18; 95% CI: 1.08-1.30) and 535 colorectal cancers were observed versus 464.6 expected (SIR = 1.15; 95% CI: 1.06-1.25). When basal cell, squamous cell and skin melanoma were considered separately, all the SIRs for prostate, breast and colorectal cancers were around or slightly above unity. Likewise, the results were consistent across strata of age at skin cancer diagnosis and location (head and neck versus others), and for male and female colorectal cancers. These findings, based on a population with a long tradition of systematic histologic examination of all surgically treated skin lesions, do not support the hypothesis that prostate, breast and colorectal cancer risk is decreased following skin cancer.     

Incidence of bone and soft tissue sarcoma after radiotherapy: a cohort study of 295,712 Finnish cancer patients

Radiotherapy is commonly used for treatment of malignant disease. As a consequence of radiotherapy, an increased risk of developing a second malignant neoplasm has been shown. However, little is known about the effects of radiation on developing sarcoma. The aim of this study was to examine the risk of developing a bone or soft tissue sarcoma after radiotherapy for a first primary cancer. The study population included all the patients with primary cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, rectum and lymphoma diagnosed during 1953-2000 and identified from the Finnish Cancer Registry. Patients were followed up for subsequent sarcomas. The follow-up yielded 1.5 million person-years at risk and 147 sarcomas. Compared to the national incidence rates, after 10 years of follow-up sarcoma risk was increased among patients who had received neither radiotherapy nor chemotherapy (standardised incidence ratio (SIR) 2.0, 95% CI 1.3-3.0), radiotherapy without chemotherapy (SIR 3.2, 95% CI 2.3-4.3), chemotherapy without radiotherapy (SIR 4.9, 95% CI 1.0-14.4), as well as combined radiotherapy and chemotherapy (SIR 3.4, 95% CI 0.4-12.5). For radiotherapy in ages below 55 the SIR was 4.2 (95% CI 2.9-5.8). In the adjusted regression analysis the rate ratio was 1.5 (95% CI 0.9-2.6) for the radiotherapy group. In conclusion, radiotherapy appears to be associated with an increased risk of developing sarcoma especially among younger patients. Further investigation is needed to clarify the dose-response of the preceding ionizing radiation.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.     

Impact of radiotherapy in the risk of esophageal cancer as subsequent primary cancer after breast cancer

PURPOSE: To assess the risk of esophageal cancer as second cancer among breast-cancer patients treated with radiotherapy. METHODS AND MATERIALS: The records of the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients were treated with surgery (n = 33,672), radiotherapy (n = 35,057), chemotherapy and radiotherapy (n = 4673), or chemotherapy (n = 2,447). The risk of a new primary cancer was expressed as standardized incidence ratio (SIR), defined as the ratio of observed to expected cases. RESULTS: By the end of 2000, the number of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among patients followed for 15 years and treated with radiotherapy, the SIR for esophageal cancer was 2.3 (95% CI = 1.4 to 5.4). No increase in risk was seen for patients treated without radiotherapy. The risk of esophageal cancer was increased among patients diagnosed during 1953 to 1974, although age at the treatment did not have marked effect on the risk estimate. CONCLUSION: Increased risk of second cancer in the esophagus was observed for breast-cancer patients in Finland, especially among patients with over 15 years of follow-up and treated in the earliest period, which may relate to the type of radiotherapy.     

Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.     

High constant incidence of second primary colorectal cancer

Patients who had a colorectal cancer have a 1.5‐ to 2‐fold excess risk of a second colorectal cancer as compared to the general population, the excess being higher at younger age at diagnosis. To further investigate the risk and the age‐relation of the incidence of second primary colorectal cancer, we considered 9,389 first colon and rectal cancers registered in the Vaud Cancer Registry, Switzerland, between 1974 and 2008, and followed‐up to the end of 2008 for a total of 44,113 person‐years. There were 136 second colorectal cancers versus 90.5 expected, corresponding to a standardized incidence ratio (SIR) of 1.5 (95% confidence interval, CI, 1.3–1.8). The SIRs were not heterogeneous between men and women, and in strata of calendar year at diagnosis, duration of follow‐up, and subsite. However, the SIR was 7.5 (95% CI 4.2–12.4) for subjects diagnosed below age 50 and declined thereafter to reach 1.0 (95% CI 0.6–1.6) at age 80 or over. Consequently, the incidence of second primary colorectal cancer was stable, and exceedingly high, around 300–400/100,000 between age 30–39 and 70 or over. This age pattern is consistent with the existence of a single mutational event in a population of highly susceptible individuals.     

Cancer risk after radiotherapy for breast cancer

Among women with breast cancer, we compared the relative and absolute rates of subsequent cancers in 1541 women treated with radiotherapy (RT) to 4570 women not so treated (NRT), using all registered in the Swiss Vaud Cancer Registry in the period between 1978 and 1998, and followed up to December 2002. Standardised incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) were based on age- and calendar year-specific incidence rates in the Vaud general population. There were 11 lung cancers in RT (SIR = 1.40; 95% CI: 0.70-2.51) and 17 in NRT women (SIR = 0.76; 95% CI: 0.44-1.22), 72 contralateral breast cancers in RT (SIR = 1.85; 95% CI: 1.45-2.33) and 150 in NRT women (SIR = 1.38; 95% CI: 1.16-1.61), and 90 other neoplasms in RT (SIR = 1.37; 95% CI: 1.10-1.68) and 224 in NRT women (SIR = 1.05; 95% CI: 0.91-1.19). Overall, there were 173 second neoplasms in RT women (SIR = 1.54, 95% CI: 1.32-1.78) and 391 among NRT women (SIR = 1.13, 95% CI: 1.02-1.25). The estimates were significantly heterogeneous. After 15 years, 20% of RT cases vs 16% of NRT cases had developed a second neoplasm. The appreciable excess risk of subsequent neoplasms after RT for breast cancer must be weighed against the approximately 5% reduction of breast cancer mortality at 15 years after RT.     

Associations between small intestine cancer and other primary cancers: an international population-based study

Cancer of the small intestine is a rare neoplasm, and its etiology remains poorly understood. Analysis of other primary cancers in individuals with small intestine cancer may help elucidate the causes of this neoplasm and the underlying mechanisms. We included 10,946 cases of first primary small intestine cancer from 13 cancer registries in a pooled analysis. The observed numbers of 44 types of second primary cancer were compared to the expected numbers derived from the age-, gender- and calendar period-specific cancer incidence rates in each registry. We also calculated the standardized incidence ratios (SIR) for small intestine cancer as a second primary after other cancers. There was a 68% overall increase in the risk of a new primary cancer after small intestine carcinoma (SIR = 1.68, 95% confidence interval [CI] = 1.47-1.71), that remained constant over time. The overall SIR was 1.18 (95% CI = 1.05-1.32) after carcinoid, 1.29 (1.01-1.63) after sarcoma, and 1.27 (0.78-1.94) after lymphoma. Significant (p < 0.05) increases were observed for cancers of the oropharynx, colon, rectum, ampulla of Vater, pancreas, corpus uteri, ovary, prostate, kidney, thyroid gland, skin and soft tissue sarcomas. Small intestine cancer as a second primary was increased significantly after all these cancers, except after oropharyngeal and kidney cancers. Although some of the excess may be attributable to overdiagnosis, it is plausible that most additional cases of second primary cancers were clinically relevant and were due to common genetic (e.g., defects in mismatch or other DNA repair pathways) and environmental (e.g., dietary) factors.     

Increased Risk of Second Primary Malignancies in Patients with Gynecological Cancer: A Swedish record-linkage study

The Stockholm-Gotland Cancer Register was used to study the risk of developing second primary malignancies (SPM) in women diagnosed with cancer of the uterine cervix, uterine corpus and ovaries during the period 1958-1992. Among 5 325 patients with uterine cervix cancer, 619 developed SPM. Standardized incidence ratio (SIR) was 1.29 (95% confidence interval (CI) 1.19-1.39). Significantly increased risks were observed for cancer of the colon, rectum, lung, vulva, kidney and bladder. A total of 4 815 women with uterine corpus cancer were followed and 660 SPM were found. The overall SIR was 1.21 (95% CI 1.12-1.30) with significantly increased risk for cancer of the colon, ovary, vulva and bladder. The incidence of leukemia was also significantly elevated (SIR = 3.03; 95% CI 1.70-5.00). Among 5060 patients with ovarian cancer, 379 SPM were found (SIR 1.49; 95% CI 1.34-1.64). Increased risks of cancer of the colon, rectum, breast, uterine corpus, bladder and leukemia were observed. All three primary sites showed elevated risks of cancer of the colon and bladder. For patients with a primary cancer of the corpus and ovary an elevated risk of leukemia was also noted. The conclusion from these findings is that SPM to some extent can be explained by previously known factors, i.e. treatment and common risk factors. However, further studies concerning the role of common etiology, for instance hereditary and hormonal factors, are needed to increase the knowledge on the etiology of second primary malignancies.     

Risk of second primary cancer among patients with early operable breast cancer registered or randomised in Danish Breast Cancer cooperative Group (DBCG) protocols of the 77, 82 and 89 programmes during 1977-2001

Breast cancer survivors have increased risks of developing second primary cancers due to shared etiology, life style factors but also to primary breast cancer treatment. Among 53 418 patients registered by the population based Danish Breast Cancer Cooperative Group (DBCG) during 1977-2001, 31 818 patients were treated and followed according to guidelines of DBCG. In addition to surgery 23% received tamoxifen, 23% chemotherapy and 35% radiotherapy as treatment for primary breast cancer. Second primary cancers were identified by linkage to the population based Danish Cancer Register. Cancer incidence rates of the Danish population were used for calculation of standardized incidence ratios (SIRs). Time at risk was from diagnosis of breast cancer+1 year until death or through 2002. Risk for all second primary cancers combined was increased, SIR=1.04 (95% confidence interval 0.99-1.08). Sites with significantly elevated risks included corpus uteri (SIR=1.23), ovary (1.39), soft tissues (2.24), acute leukaemia (2.02), and sites potentially inducible by breast cancer radiotherapy combined (1.11). For irradiated patients compared to non-irradiated the risk was increased for all sited combined, radiotherapy-related sites, colon and soft tissues. Tamoxifen treated had, compared to non-treated, elevated risk for cancer of corpus uteri (SIR=1.83 vs 1.04). Patients given adjuvant chemotherapy had, compared to those not, elevated risks for all sites combined (SIR=1.24 vs 1.01) and for ovary (2.16 vs 1.24). Risk for cancer of the lung, uterus and ovary was analysed using multivariate Poisson regression. For lung cancer the risk was related to radiotherapy and time since diagnosis, the relative risk for lung cancer being 1.33 (95% CI 1.00-1.77) (irradiated vs non-irradiated). Ovary cancer risk was inversely related to age at diagnosis but not to treatment and corpus uteri cancer risk related to tamoxifen treatment, relative risk 1.57. The findings are in accordance to other population based studies.     

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.     

Risk of malignancy among patients with rheumatic conditions

Previous studies have described an increased risk of malignancy in subjects diagnosed with rheumatic conditions, most notably rheumatoid arthritis (RA). Our aim was to quantify and compare risks for site-specific malignancy among hospitalized patients with RA, osteoarthritis (OA) and other rheumatic conditions in a nationwide, population-based cohort. Subjects were identified from Scottish hospital in-patient records from 1981 to 1996 and followed up by computer linkage of the Scottish Cancer Registry and the national registry of deaths. Expected cancer incidence was calculated from national cancer rates and related to the observed incidence by the standardized incidence ratio (SIR). Among RA patients, there was an increased risk for hematopoietic [males SIR= 2.13, 95% confidence interval (CI) 1.7-2.7; females SIR = 1.76, 95% CI 1.5-2.1], lung (males SIR = 1.32, 95% CI 1.2-1.5; females SIR = 1.44, 95% CI 1.3-1.6) and prostate (SIR = 1.26, 95% CI 1.0-1.6) cancers. Reduced risk were seen for colorectal cancer (males SIR = 0.87, 95% CI 0.7-1.1; females SIR = 0.71, 95% CI 0.6-0.9) and, among females, stomach cancer (SIR = 0.70, 95% CI 0.5-1.0). The excess risk for hematopoietic cancer and the reduced risk for colorectal and stomach cancers were sustained over 10 years of follow-up. An overall decreased risk of cancer was observed for patients with OA; the greatest reductions were observed for colorectal (males SIR = 0.88, 95% CI 0.8-1.0; females SIR = 0.84, 95% CI 0.8-0.9), stomach (males SIR = 0.79, 95% CI 0.7-0.9; females SIR = 0.66, 95% CI 0.6-0.8) and lung (males SIR = 0.72, 95% CI 0.7-0.8; females SIR = 0.84, 95% CI 0.8-0.9) malignancies, with decreased risks generally still evident at 10 years of follow-up. Our results support several previous findings regarding the incidence of hematopoietic and colorectal malignancies in RA patients. In addition, we have shown a large decrease in stomach cancer among patients with OA and females with RA that warrants further investigation since it may provide clues to possible prevention strategies. To further our knowledge about the underlying mechanisms of altered risk in cancer patients with rheumatic conditions, population studies requiring primary data collection are required.     

Acromegaly and cancer risk: a cohort study in Sweden and Denmark

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977–1993; Sweden 1965–1993) were linked to tumor registry data for up to 15–28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5, 95% CI = 1.3–1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.6–2.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2–17.4), colon (SIR = 2.6, 95% CI = 1.6–3.8), and rectum (SIR = 2.5, 95% CI = 1.3–4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI = 1.2–5.0), thyroid (SIR = 3.7, 95% CI = 1.8–10.9), kidney (SIR = 3.2, 95% CI = 1.6–5.5), and bone (SIR = 13.8, 95% CI = 1.7–50.0). Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-1 system in the etiology of various cancers.     

Haemochromatosis and gastrointestinal cancer

Iron overload in patients with haemochromatosis is a strong risk factor for liver cancer, but its influence on other gastrointestinal cancer risk is unclear. The aim was to assess the relative risk of luminal gastrointestinal cancer among patients diagnosed with haemochromatosis. This population‐based, nationwide Swedish cohort study included patients with haemochromatosis in Sweden in 1965–2013. The incidence of gastrointestinal cancers was assessed through the Swedish Cancer Registry. The measure of relative risk was the standardised incidence ratio (SIR) with 95% confidence interval (CI), that is, the ratio of the observed number of gastrointestinal cancers in the haemochromatosis cohort divided by the expected number of such cancers, calculated from the entire corresponding background population of Sweden. Among 6,849 patients in the haemochromatosis cohort with up to 48 years of follow‐up, the SIRs were 3‐fold increased for oesophageal squamous cell carcinoma (SIR = 3.2, 95% CI 1.3–6.6; n = 7) and 40% increased for colon adenocarcinoma (SIR = 1.4, 95% CI 1.1–1.9; n = 54). No associations were found between haemochromatosis and the risk of adenocarcinoma of the oesophagus (SIR = 0.5, 95% CI 0.0–2.5; n = 1), stomach (SIR = 0.7, 95% CI 0.3–1.4; n = 8), small bowel (SIR = 1.2, 95% CI 0.0–6.7; n = 1) or rectum (SIR = 1.0, 95% CI 0.6–1.6; n = 21). These findings indicate that haemochromatosis increases the risk of oesophageal squamous cell carcinoma and colon adenocarcinoma, but might not influence the risk of other types of luminal gastrointestinal cancer. These findings should encourage further research examining the role of iron overload in cancer aetiology.     

Second Primary Cancers Following Colon and Rectal Cancer in Osaka, Japan

The frequencies of second primary cancers following colon and rectal cancers were estimated using the Osaka Cancer Registry's population-based data for Osaka, Japan. A series of 7,312 colon and 6,923 rectal cancer cases newly diagnosed in the period of 1966-1986 were followed up until the end of 1986. The average follow-up period was 3.6 years for colon cancer and 3.7 years for rectal cancer. Significantly elevated risks of second primary cancers following colon cancer were observed for cancers of the rectum (O/E= 2.0; 95% confidence interval (CI) = 1.1-3.4 among males, O/E=4.3; 95% CI=2.4-7.2 among females), corpus uteri (O/E=8.2; 95% CI = 3.3-16.9), ovary (O/E=4.3; 95% CI = 1.0-5.0), and female thyroid gland (O/E=4.7; 95% CI=1.7-8.8). These findings were more notable among right-sided colon cancer patients than left-sided colon cancer patients. The elevated risks of second primary cancers were particularly evident among patients younger than 50 years of age at the time of diagnosis of the initial cancer (colon cancer: O/E = 3.1 among males, 3.4 among females, rectal cancer: O/E=1.7 among males, 1.3 among females). These findings suggest that younger colorectal cancer patients should undergo more careful checkups throughout their lives.