Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.     

Multiple primary breast and thyroid cancers: role of age at diagnosis and cancer treatments (United States)

Background:Breast and thyroid cancer have been observed to occur more frequently than expected as multiple primary tumors in women. The study presented herein focuses on the effects of age at diagnosis and treatment for the first cancer on the development of the second cancer. Methods:This retrospective cohort study used a study population consisting of 38,632 women diagnosed with primary invasive breast cancer and 2189 women diagnosed with primary invasive thyroid cancer between 1974 and 1994. Cases were identified from records of the Cancer Surveillance System of western Washington and followed for subsequent cancer development through 1995. Results:Seventy-one women were diagnosed during their lives with both breast and thyroid cancers. Including cancers diagnosed during the same month as or after the initial cancer, the relative risk (RR) of breast cancer among women with thyroid cancer was 1.5 (95% confidence interval [CI] 1.1–2.0), and the RR of thyroid cancer among women with breast cancer was 1.5 (95% CI 1.1–2.2). Among women with thyroid cancer, risk of breast cancer was greatest when the latter cancer was diagnosed under 45 years of age (RR = 2.3, 95% CI 1.1–4.4). First course of treatment, including radiation or hormonal therapy to treat thyroid cancer, and radiation, chemotherapy, or hormonal therapy to treat breast cancer, did not alter a woman's risk of developing the second cancer. Conclusions:The data suggest that the incidence of breast and thyroid cancer may be related, and that in particular women with thyroid cancer may be at a moderately increased risk of developing breast cancer before age 45.     

Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States)

Objectives: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. Methods: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. Results: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9–1.0); prostate (RR = 1.0, 95% CI = 0.9–1.1); colon (RR = 0.9, 95% CI = 0.7–1.2); or lung (RR = 0.9, 95% CI = 0.7–1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7–1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8–1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7–1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6–1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3–0.8). Conclusions: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.     

Second Primary Cancer after Diagnosis of Stomach Cancer in Osaka, Japan

The risk of developing a second primary cancer following stomach cancer was estimated from data accumulated in the Osaka Cancer Registry. Of the 38,777 male patients and 22,391 female patients newly diagnosed in the period 1966–1986 who were followed up until the end of 1986, 778 and 267 developed a second cancer other than stomach cancer, respectively, whereas the expected numbers had been 928.8 (RR=0.84, 95%CI=0.78-0.90) and 297.7 (RR = 0.90, 95%CI = 0.79-1.01). The risks were higher among younger patients (aged 30–54 at the diagnosis of stomach cancer) than among older patients (aged 55–69 at the diagnosis of stomach cancer). Significantly elevated risks were observed for cancers of the oral cavity & pharynx (RR=l.56), colon (RH = 1.61) and rectum (RR = 1.56) for males, and oral cavity & pharynx (RR = 2.59) for females as second cancers. Results were substantially similar among the localized stomach cancer patients. Among younger male patients with gastrectomy, the risk of developing pancreatic cancer was elevated 10 or more years after stomach cancer diagnosis. The present study suggests the necessity of following up stomach cancer patients in order to enable the early diagnosis of digestive tract cancer.     

Second primary cancer after treatment for cervical cancer. Late effects after radiotherapy

Using data from the population-based Danish Cancer Registry, the relative risk (RR) of second primary cancer was assessed among 24,970 women with invasive cervical cancer (1943-1982) and 19,470 women with carcinoma in situ of the cervix. The analysis was stratified according to treatment with (+) and without (-) radiation. For all second primaries combined, a RR+ = 1.1 (95% confidence interval (CI) = 1.06-1.18) and a RR- = 1.3 (95% CI = 1.13-1.40) was observed after invasive cervical cancers and a RR+ = 3.5 (95% CI = 1.4-7.2) and RR- = 1.1 (95% CI = 0.7-1.6) following in situ cancer. The small overall excess of second primary cancer is accounted for by an increase of some cancers such as lung, bladder, and a concurrent decrease in others such as breast. Although not statistically different from nonirradiated, the RR increased with time since treatment among irradiated invasive cervical cancer patients in organs close to and at intermediate distance from the cervix, reaching a maximum after 30 or more years of follow-up (RR = 1.9; 95% CI = 1.4-2.5). Altogether, for these sites an excess of 64 cases per 10,000 women per year were attributable to radiation among survivors of 30+ years. The highest risks among long-term survivors were observed for the following: other genital organs (RR = 5.8; 95% CI = 1.8-13.0) bladder (RR = 5.5; 95% CI = 2.8-9.5), connective tissue (RR = 3.3; 95% CI = 0.4-12.0), stomach (RR = 2.5; 95% CI = 1.1-4.7) and rectum (RR = 2.4; 95% CI = 1.1-4.6). A significant deficit of risk for breast cancer (RR = 0.7, 95% CI = 0.6-0.8) was observed for 10+ years, may be attributable to the effect of ovarian ablation by radiotherapy. It is speculated that the same effect also may explain the observed deficits of brain tumors (RR = 0.6; 95% CI = 0.4-1.0) and skin melanomas (RR = 0.6; 95% CI = 0.3-1.0). It is concluded that cancers attributable to radiation, apart from acute nonlymphocytic leukemias, tend to appear late (10 or more years after radiotherapy), and that the risk remains elevated for more than 30 years.     

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

Background:

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

Methods:

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

Results:

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

Conclusions:

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

Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States)

Objective: This study evaluated the joint effects of tobacco smoking and alcohol consumption on the risk of second primary tumors (SPT) in patients with early-stage head and neck squamous cell carcinoma (HNSCC). Methods: Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development. Results: After adjusting for the time from the index diagnosis to randomization, age at diagnosis, stage, and site of the primary cancer, the factors that emerged as simultaneous predictors of SPT development were continued smoking and alcohol intake after the index diagnosis. Increased SPT risk was associated with older age (RR = 2.1; 95% CI 1.5–2.8); stage II diagnosis (RR = 1.5; 95% CI 1.1–2.1); index diagnosis of pharyngeal cancer (RR = 1.6; 95% CI 1.1–2.5); current smoking at registration (RR = 2.1; 95% CI 1.3–3.6) and continued alcohol consumption post-diagnosis (RR = 1.3; 95% CI 1.0–1.7). Conclusion: Important associations exist between SPT development and continued smoking and alcohol consumption after treatment for HNSCC.     

Second malignancies following pure seminoma

PURPOSE: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. PATIENTS, METHODS: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the study because they already had had either a contralateral testicular germ cell tumor or another malignancy. 758 patients received radiotherapy, 76 underwent chemotherapy, 5 had surveillance only. The expected rate of second cancers was calculated according to the data of the cancer registry of Saarland, Germany. RESULTS: Twenty-two second cancers (13 contralateral testicular tumors, 9 extratesticular malignancies) were recorded. The overall risk of having a second cancer was RR = 4.8 (95% CI 3. 0-7.3). The risk of having a subsequent testicular tumor is RR = 44. 8 (95% Cl 23.9-76.7). 1.1% of the patients developed a nontesticular second tumor. The risk of having a nontesticular second cancer is RR = 2.1 (95% CI 1.0-4.0). A significantly increased risk was observed for renal cell cancer as well (RR = 12.5; 95% Cl: 1.5-45.1). Increased RR without reaching statistical significance were found for rectal cancer (RR = 5.0; 95% Cl: 0.1-27.9) and non-Hodgkin lymphoma (RR = 6.7; 95% CI 0.2-37.1). None of the second cancers were directly located within the radiation field; 5 neoplasms arose at the border of the radiation field. CONCLUSIONS: This study confirmed the increased risk of having a second testicular germ cell cancer. There is also a small but definitely increased overall risk of having a nontesticular second cancer. Treatment-unrelated factors - possibly genetic predisposition - must be considered for a substantial number of these second tumors, since in the present study the follow-up was rather short and most of the second cancers were located outside of the radiation fields. In particular, the association of renal cancer with testicular cancer appears to be a more than chance occurrence. Second cancer is a real hazard following treatment of testicular cancers and should always be considered during follow-up.     

Employment as butcher and cancer risk in a record-linkage study from Sweden

Objective: To investigate the risk of cancer among butchers and other meat workers in a large record-linkage study from Sweden. Methods: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971–1989 for all residents, by occupation and industry of employment as reported at the 1960 and 1970 censuses. We identified 25,049 men classified as butchers or meat workers at either census. We used as a comparison group the remaining part of the active male population, after exclusion of workers with direct contact with animals. Results: Butchers in the meat industry had a slight increase in the risk of cancer (relative risk [RR] 1.1, 95% confidence interval [CI] 1.0–1.3), which was due to an increased risk of cancers of the oral cavity and pharynx (RR 1.6, 95% CI 1.0–2.7), stomach (RR 1.6, 95% CI 1.1–2.7), larynx (RR 1.4, 95% CI 0.6–3.4), and lung (RR 1.4, 95% CI 1.1–1.9). The risk of stomach cancer was highest during the first 5 years of the study, and among butchers from urban areas. No temporal or geographic variations were seen for lung cancer risk, with elevations restricted to squamous cell carcinoma. An increased risk of stomach, laryngeal and lung cancers was present in butchers and meat workers outside the meat industry. There was no clear indication of an increased risk of other neoplasms. Conclusions: The increased risk of oral, laryngeal, lung and stomach cancers among Swedish butchers may be at least partly due to confounding by tobacco smoking, alcohol drinking, and other lifestyle factors. However, exposures in the meat industry (e.g., viruses, nitrosamines, polycyclic aromatic hydrocarbons) may contribute the elevated cancer risks.     

Second primary cancers in patients with laryngeal cancer: a population-based study

BACKGROUND: Literature regarding incidence of site-specific second cancers after laryngeal cancer is limited. Risk factors associated with second primaries are unknown. METHODS: Second primaries after laryngeal cancer in the SEER database (1973-1996) were analyzed for incidence, relative risk compared with the general population, and potential risk factors, including radiotherapy. Information on chemotherapy and tobacco smoking was not available in the SEER database. RESULTS: Of 20,074 laryngeal cancer patients surviving at least 3 months, 3533 (17.6%) developed second cancers. The cumulative risk of developing a second cancer was 26% at 10 years and 47% at 20 years. Compared with age-adjusted, gender, and tumor-specific rates in the general population, laryngeal cancer patients had higher risks of second cancers overall (observed-to-expected ratio [O/E] = 1.68, 95% confidence interval [CI] = 1.58-1.79), head-and-neck (4.81 [4.31-5.58]), esophageal (3.99 [3.29-4.83]), and lung (3.56 [3.34-3.79]) cancer. Advanced age at initial diagnosis was associated with increased risks of second cancers (p = 0.0001). Radiotherapy was associated with increased risk of second cancers overall (relative risk [RR] = 1.10 [1.02-1.18], p = 0.012), especially second cancers of the lung (RR = 1.18, [1.05-1.33], p = 0.006) and possibly second cancers of the head and neck (RR = 1.26, [0.99-1.60], p = 0.061). Radiotherapy was associated with a 68% excess risk (RR = 1.68, [1.16-2.43], p = 0.007) of developing a second head-and-neck cancer in patients who survived more than 5 years. Second primary was associated with a poor survival (p = 0.0001). CONCLUSIONS: Second cancers after laryngeal cancer are common, especially for long-term survivors. Radiotherapy was associated with a small increased risk of developing second cancers overall and long-term risk of head-and-neck cancers. This data should be interpreted with caution in light of the lack of information on chemotherapy and tobacco smoking in the SEER database. Prevention and early detection are indicated.     

Second Primary Cancers Following Female Breast Cancer in Osaka, Japan--A Population-Based Cohort Study

Using the data accumulated in the Osaka Cancer Registry, a cohortstudy was conducted on the occurrence of second primary cancersfollowing the first breast cancer in females. Of the 9, 503breast cancer patients newly diagnosed in the period 1965–1982who were followed up until the end of 1983 (average follow-upperiod, 5.7 years), 344 developed second cancers, whereas theexpected number had been 211 (relative risk (RR) = 1.6; 95%confidence interval (CI) = 1.5–1.8). The increased riskwas observed throughout the observation period, and was higherin patients of less than 45 years of age at diagnosis than inolder women. Significant excess risks were found for secondcancers of the opposite breast (RR = 4.2; 95% CI = 3.4–5.2),buccal cavity (RR = 3.6; 95% CI = 1.6–7.2), stomach (RR= 1.4; 95% CI = 1.2–1.8), colon (RR = 1.8; 95% CI = 1.1–2.1)and thyroid gland (RR = 3.2; 95% CI % 1.5–6.1). The effectsof chemo- and radiotherapy administered for initial breast canceron the increased risk of the above mentioned second cancerswere also examined. These therapeutic measures were found notlikely to be related to the excess risks for cancers of thebuccal cavity, stomach and colon. For second cancer of the oppositebreast, however, both chemotherapy and radiotherapy remainedas possible risk factors. The effect of radiation was proposedas being a likely explanation for the excess risk of secondthyroid cancer.     

Dietary Habits and Cancer Mortality Among Middle Aged and Older Japanese Living in Hokkaido,Japan by Cancer Site and Sex

Dietary factors are thought to be closely associated with the development of human cancers and hence numerous studies ‍in this area have already been conducted in the United States and other Western countries. Comparatively few prospective ‍studies have been published in Japan, especially for Hokkaido people. The present investigation was therefore performed to ‍assess links between four leading cancers and some of the Japanese common dietary factors through a cohort study (1984- ‍2002) in Hokkaido by analyzing 1,524 men and 1,634 women separately aged 40 and over. Adjusted Cox proportional ‍hazard regression was used to calculate the relative risk (RR) for each dietary factor. For men, two dietary factors, miso ‍soup (RR=0.2, 95% confidence interval (95%CI)=0.1-0.8) and pickled vegetables (RR=0.2, 95%CI=0.1-0.8) were associated ‍with lower risk for stomach and colorectal cancer respectively. For women, three factors, namely salty confectionary (RR=3.5, ‍95%CI=1.1-10.9), black tea (RR=3.8, 95%CI=1.1-13.6), and carbonated drink/juice (RR=3.9, 95% CI=1.4-11.1) appeared ‍related to an elevated risk of stomach cancer. However, further analysis simultaneously with all other adjusted factors ‍indicated only carbonated drink/juice (RR=3.1, 95%CI=1.1-8.9) to present a significant risk factor for stomach cancer. One ‍factor, namely wild edible plants (RR=3.3, 95%CI=1.1-9.8), increased the risk for colorectal cancer in women. None of the ‍dietary components were significantly associated with lung or pancreatic cancers. This study also indicated a wide variation ‍in the impact of dietary factors by sex and cancer site, in line with earlier work, poonting to a necessity for careful interpretation. ‍Further epidemiological investigations by sex with more study subjects and confounding factors will be useful for determining ‍the contribution of individual dietary factors to development of human cancers in Hokkaido, Japan.     

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.     

Association of basal cell skin cancers with other cancers (United States)

Background: Persons with basal cell skin cancer (BCSC) have shown increased risk of developing cancer at several other sites. Methods: We identified 3164 persons with BCSC and 15,730 comparison subjects matched for age, sex, race, residence area and length of membership in a health maintenance organization. Results: In retrospective follow-up for up to 24 years (mean 11.3 years), BCSC patients experienced statistically significant increases in the incidence of all cancer (relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1–1.4) lung cancer (RR = 1.4, CI = 1.0–1.8) and melanoma (RR = 2.2, CI = 1.6–3.0). Women experienced significantly increased risk for all cancer, lung cancer, melanoma and thyroid cancer, increases of borderline significance in breast cancer, non-Hodgkin's lymphoma and leukemia, and increased pre-existing bladder cancer. Men showed statistically significant increases in all cancer, melanoma, and kidney cancers, and mouth and throat cancers. Multivariate analysis incorporating available risk factor data did not weaken positive associations with BCSC except slightly for melanoma and for bladder cancer in women. Other previously reported associations were not confirmed. Conclusion: Periodic skin examinations appear well justified after removal of BCSC to detect new skin cancers including melanoma. Given the relatively weak, unexplained associations of BCSC with internal cancers, the costs vs. benefits of extra efforts to detect the latter still need to be determined.     

Risk factors for metachronous contralateral breast cancer suggest two aetiological pathways

Although many studies show an increased risk of metachronous contralateral breast cancer (CBC) in women with a positive family history and young age at diagnosis of the initial breast cancer, the aetiological pathways are still enigmatic.In a cohort of 8478 primary breast cancer patients diagnosed between 1975 and 2006, 558 cases of metachronous CBC were identified. Using multivariate Cox proportional hazards models, we analysed risk factors assessed at the time of the first primary tumour, including patient demographics, tumour characteristics and treatment among 4681 breast cancer patients for whom data on key variables were available. The analysis was performed separately in patients who developed CBC without and with prior recurrence(s).Risk of CBC without prior recurrent disease was increased by a positive family history [adjusted relative risk (RR) 2.8 (95% confidence interval (CI) 1.4-5.5)]; and decreased by endocrine treatment [RR 0.6 (95% CI 0.4-1.0)]. We found an increased risk of CBC with prior recurrent disease with younger age [RR 1.2 (95% CI 1.4-3.0)]; positive family history [RR 2.1 (95%CI 0.8-5.0)]; and extensive lymph node involvement [RR 2.0 (95% CI 1.2-3.6)].Our results suggest that nodal status of the primary tumour may be as important a risk factor as family history or age, which indicates a high susceptibility to breast cancer or an impaired host defence mechanism. It may also imply that some CBCs are metastases from the first primary tumour, particularly in patients who present with recurrent disease before CBC.     

Risk of cancer in a large cohort of U.S. veterans with diabetes

Prior studies of cancer risk among diabetic men have reported inconsistent findings. The aim of this study was to assess the risk of cancer among a large cohort (n = 4,501,578) of black and white U.S. veterans admitted to Veterans Affairs hospitals. The cancer risk among men with diabetes (n = 594,815) was compared to the risk among men without diabetes (n = 3,906,763). Poisson regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Overall, men with diabetes had a significantly lower risk of cancer (RR = 0.93, 95%CI = 0.93–0.94). Men with diabetes, however, had increased risks of cancers of the liver (RR = 1.95, 95%CI = 1.82–2.09), pancreas (RR = 1.50, 95%CI = 1.42–1.59), biliary tract (RR = 1.41, 95%CI = 1.22–1.62), colon (RR = 1.20, 95%CI = 1.16–1.25), rectum (RR = 1.12, 95%CI = 1.07–1.18), and kidney (RR = 1.09, 95%CI = 1.03–1.16), as well as leukemia (RR = 1.14, 95%CI = 1.08–1.21) and melanoma (RR = 1.13, 95%CI = 1.03–1.24). In contrast, men with diabetes had decreased risks of cancers of the prostate (RR = 0.89, 95%CI = 0.87–0.91), brain (RR = 0.91, 95% CI = 0.82–0.99), buccal cavity (RR = 0.85, 95%CI = 0.82–0.89), lung (RR = 0.79, 95%CI = 0.77–0.80), esophagus (RR = 0.77, 95%CI = 0.72–0.82), and larynx (RR = 0.76, 95%CI = 0.71–0.80). These findings indicate that black and white men with diabetes are at significantly lower risk of total cancer and of two of the most common cancers among U.S. males; lung and prostate cancers. These decreased risks were offset, however, by increased risks of cancer at several sites. Hyperinsulinemia may explain the increased risks of the digestive cancers, while lower testosterone levels, in the case of prostate cancer, and higher BMI, in the case of lung cancer, may explain the decreased risks of those tumors.     

Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: a prospective cohort study

OBJECTIVES: This study prospectively evaluated the associations of human T-lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence. METHODS: The study base comprised 4297 adults (aged 40-69 years in 1993) who had either visited the outpatient clinic or who had received annual health check-ups at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261 cases of malignant neoplasms occurred, including ten deaths and six incident cases of adult T-cell leukemia/lymphoma (ATL). RESULTS: After adjustment for gender, age and other covariates, HTLV-I seropositivity was associated with an increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95% confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated with an increased risk of developing total cancers other than ATL (RR = 0.98, 95% CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99). CONCLUSIONS: HTLV-I infection is associated with increased mortality from all-causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be at increased general cancer risk, but at reduced risk of gastric cancer.     

The metabolic syndrome and risk of incident colorectal cancer

BACKGROUND: The authors tested the hypothesis that the metabolic syndrome (> or =3 of the following components: high blood pressure, increased waist circumference, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, or diabetes/hyperglycemia) is a risk factor for colorectal cancer. METHODS: Data from the Atherosclerosis Risk in Communities (ARIC) multicenter prospective cohort study were used. Metabolic syndrome components and other risk factors were collected during 1987 to 1989 from the 14,109 men and women in these analyses. One hundred ninety-four incident colorectal cancers were identified through the Year 2000. Multivariate Cox proportional hazards regression analyses were used to examine associations. RESULTS: Baseline metabolic syndrome (> or =3 components vs. 0 components) had a positive association with age-adjusted and gender-adjusted colorectal cancer incidence (relative risk [RR], 1.49; 95% confidence interval [95%CI], 1.0-2.4); this association was attenuated after multivariate adjustment (RR, 1.39; 95%CI, 0.9-2.2). There was a dose-response association between colorectal cancer incidence and the number of metabolic syndrome components present at baseline (P for trend = .006) after multivariate adjustment. Analysis of gender revealed that the multivariate-adjusted association of metabolic syndrome with colorectal cancer was stronger in men (RR, 1.78; 95%CI, 1.0-3.6) and weaker in women (RR, 1.16; 95%CI, 0.6-2.2). CONCLUSIONS: In this population-based cohort, metabolic syndrome was a risk factor for incident colorectal cancer in men but not women. Evidence is growing that the metabolic syndrome may be a marker for a physiologic milieu of growth that encourages tumor initiation, promotion, and/or progression.     

Second primary cancers following cancers of the kidney and prostate in New South Wales (Australia), 1972–91

Data from the New South Wales (NSW) (Australia) Central Cancer Registry for the period 1972–91 were examined to determine the risk of second primary cancers following an initial invasive cancer of the renal parenchyma (ICD-9 code 189.0), renal pelvis (code 189.1), or prostate (code 185). Eligible cases were restricted to those who had survived for at least two months after diagnosis of the first primary cancer. Expected numbers of cancers were obtained by assuming that subjects experienced the same cancer incidence as prevailed in the corresponding general population and applying gender-, age-, and calendar-specific rates to the appropriate person-years at risk. The relative risk (RR) of a second primary cancer was taken to be the ratio of observed to expected numbers of second cancers. Following prostatic cancer, there was an overall deficit of cancers at all sites combined (RR=0.79, 95 percent confidence interval [CI]=0.75–0.84), and no site had a significantly raised RR. Taking this into consideration, there appeared to be a reciprocal relationship of increased risk of prostatic cancer (RR=1.7, CI=1.2–2.3) following an initial cancer of the renal parenchyma and of renal parenchymal cancer (RR=1.2, CI=0.8–1.7) after cancer of the prostate. An increased risk of bladder cancer occurred following renal parenchymal (RR=3.4, CI=1.1–8.0, for women only) as well as after renal pelvic cancer (men:RR=8.7, CI=5.4–13; women:RR=39, CI=26–56). A tobacco-related pattern of excess risk was seen after renal pelvic cancer but not after cancer of the renal parenchyma. These data illustrate that an excess of second primary cancers may reflect shared etiologic factors or increased medical surveillance.Dr McCredie and Ms Coates are with the New South Wales Cancer Council in the Cancer Epidemiology Research Unit (Dr McCredie) and NSW Central Cancer Registry (Ms Coates). Dr Stewart is with the Western Clinical School, University of Sydney, Australia. Dr Macfarlane is with the ARC Epidemiology Unit, University of Manchester, UK. Address correspondence to Dr McCredie, Cancer Epidemiology Research Unit, NSW Cancer Council, PO Box 572, Kings Cross 2011, New South Wales, Australia.     

Second primary cancer after diagnosis of stomach cancer in Osaka, Japan

The risk of developing a second primary cancer following stomach cancer was estimated from data accumulated in the Osaka Cancer Registry. Of the 38,777 male patients and 22,391 female patients newly diagnosed in the period 1966-1986 who were followed up until the end of 1986, 778 and 267 developed a second cancer other than stomach cancer, respectively, whereas the expected numbers had been 928.8 (RR = 0.84, 95% CI = 0.78-0.90) and 297.7 (RR = 0.90, 95% CI = 0.79-1.01). The risks were higher among younger patients (aged 30-54 at the diagnosis of stomach cancer) than among older patients (aged 55-69 at the diagnosis of stomach cancer). Significantly elevated risks were observed for cancers of the oral cavity & pharynx (RR = 1.56), colon (RR = 1.61) and rectum (RR = 1.56) for males, and oral cavity & pharynx (RR = 2.59) for females as second cancers. Results were substantially similar among the localized stomach cancer patients. Among younger male patients with gastrectomy, the risk of developing pancreatic cancer was elevated 10 or more years after stomach cancer diagnosis. The present study suggests the necessity of following up stomach cancer patients in order to enable the early diagnosis of digestive tract cancer.