Second cancers in patients with chronic lymphocytic leukemia.

BACKGROUND: Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deficits to excesses of twofold to threefold. PURPOSE: Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site-specific excesses might be associated with type of initial treatment for CLL. METHODS: We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed at least 2 months after the initial CLL diagnosis. RESULTS: Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed; observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis. CONCLUSION: CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL, perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy.     

The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) are at increased risk for developing secondary malignancies. For the current study, the authors quantitated this risk in a group of NHL survivors over 30 years of follow-up. METHODS: Standardized incidence ratios (observed-to-expected [O/E] ratio) and absolute excess risk of secondary malignancies were assessed in 77,876 patients who were diagnosed with NHL between 1973 and 2001 from centers that participated in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: There were 5638 patients who developed secondary malignancies, significantly more than the endemic rate (O/E, 1.14; P < .001). Overall, irradiated patients had a similar risk of secondary malignancies compared with unirradiated patients (relative risk, 1.04; 95% confidence interval, 0.98-1.10; P = .21). Irradiated patients had excess risk for sarcomas, breast cancers, and mesothelioma compared with unirradiated survivors (P < .05). Patients age <25 years at the time of their NHL diagnosis had the highest relative increased risk (no radiation: O/E, 2.1; P < .05; radiation: O/E, 4.51; P < .05). Overall, no statistical difference was observed for secondary cancer incidence between females and males (O/E, 1.12 vs. 1.15, respectively). Female survivors of NHL were less likely to develop breast cancer than the general population (O/E, 0.85; P < .05), but women age <25 years at the time of their NHL diagnosis were more likely to develop breast cancer (no radiation: O/E, 2.1; P < .05; radiation: O/E, 4.51; P < .05). CONCLUSIONS: The overall risk of secondary malignancies was increased for NHL survivors and varied according to age at NHL diagnosis, gender, and treatment.     

Cancer risk among Danish male Seventh-Day Adventists and other temperance society members

Cancer risk was studied in 781 male Seventh-Day Adventists (SDA) and 808 male members of other temperance societies. Standardized morbidity ratios for all cancers were 0.69 among SDA and 1.05 among other temperants. Significantly decreased risks of cancers were noted among SDA for cancer of the colon [observed/expected (O/E): 0.13], cancer of the respiratory system (O/E: 0.17), cancer of the lung (O/E: 0.15), and cancer of the bladder including papilloma (O/E: 0.13). No significant deviations from expectations were noted among members of other temperance societies. Thus risks of tobacco-associated cancers were markedly decreased among SDA. The risk of alcohol-associated cancers (cancers of the oral cavity, pharynx, esophagus, and larynx) taken together was also decreased (O/E: 0.7), although not significantly so. When the results were compared with those of a previous study of Danish brewery workers who had a high average daily beer intake, the present investigation provides further support that the alleged association between beer consumption and the occurrence of rectal cancer is of a noncausal nature. The explanation for the decreased risk of colon cancer should probably be sought in the dietary practices of SDA.     

Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.     

Second cancers following non-Hodgkin's lymphoma

The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.     

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.     

Thyroid cancer and multiple primary tumors in the SEER cancer registries

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects.     

Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years.

PURPOSE: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin's disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment. PATIENTS AND METHODS: Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed. RESULTS: Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect. CONCLUSION: Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.     

Merkel cell carcinoma and multiple primary cancers.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for which causative factors remain largely unknown. The site-specific risks of multiple primary cancers associated with MCC, which may provide insight into etiologic influences, have not been quantified in large population-based studies. We estimated the long-term risk of subsequent primary tumors after a first primary MCC (1,306 patients) and the risk of second primary MCC following other first primary cancers (2,048,739 patients) within 11 population-based cancer registries which report to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1986-2002). Patients with first primary MCC were at significantly increased risk of developing a subsequent cancer [standardized incidence ratio (SIR), 1.22; 95% confidence intervals (95% CI), 1.01-1.45; observed (O = 122)], with significant excesses restricted to the first year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly elevated site-specific risks were observed for cancers of salivary gland (SIR, 11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95% CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were seen for chronic lymphocytic leukemia, and cancers of the small intestine and brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of MCC as a second primary malignancy was observed among patients with all other first primary cancers taken together. In particular, significant 3- to 7-fold excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4), chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR, 3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play a role, increased reciprocal risks suggest that MCC may share etiologic influences with other malignancies. Heightened awareness of the associations of lymphohematopoietic malignancies with MCC may facilitate early clinical recognition.     

Salivary gland cancer in the United States.

The risk of salivary gland cancer (SGC) is increased in atomic bomb survivors and after radiotherapy, but other risk factors are not well established. Some studies have suggested an association of SGC with breast cancer and with exposure to various viruses or UVB radiation. Corroborating evidence of these associations was sought by using population-based registries to examine the demographic distribution of SGC, patterns of secondary primary cancers after SGC, and risk of SGC with AIDS. SGC incidence per 100,000 persons did not change between 1973 and 1992, averaging 1.2 in males and 0.8 in females, with a steep age gradient. To examine the relationship between UVB exposure and SGC, population-based, age-adjusted incidence rates of SGC were plotted against the UVB insolation of each registry site. Regression analysis suggested no correlation between SGC incidence and increasing UVB insolation (beta = 0.10, R2 = 0.08). SGC also did not appear to be associated with second cancers that have been linked to herpes or papilloma viruses or with AIDS [observed/expected (O/E) ratio, <2.8], but all of these conditions are so uncommon that only very large relative risks would have been statistically significant. Women with SGC before age 35 had a statistically nonsignificant elevation in breast cancer risk [O/E, 3.30; 95% confidence interval (CI), 0.66-9.65], and older women had no increased risk of breast cancer. SGC patients were at increased risk for nonsalivary, second-primary oropharyngeal cancers (O/E, 3.27; 95% CI, 2.00-5.05), thyroid cancer (O/E, 3.31; 95% CI, 1.07-7.73), and lung cancer (O/E, 1.86; 95% CI, 1.45-2.35), particularly in patients whose SGC was treated with radiotherapy (O/E, 2.83; 95% CI, 2.06-3.80). In summary, SGC remains rare and does not appear to be associated with AIDS, virally related malignancies, or UVB. Patients who have had SGC, however, should be monitored for subsequent oropharyngeal, thyroid, and lung cancers.     

Effect of twinship on incidence of cancer of the testis,breast, and other sites (Sweden)

It has been suggested that cancers of the testis and breast are associated with exposure to estrogens and other hormones in utero. Twin pregnancies have higher levels of pregnancy-associated hormones than singleton pregnancies, and these levels may be higher in dizygotic than in monozygotic twin pregnancies. Through a large population-based study of twins, we assessed the hypothesis that levels of pregnancy-associated hormones have etiologic importance for cancers of the testis, breast, and other sites. The incidence of all cancers among 46,767 members of the Swedish Twin Registry was compared with the incidence among the Swedish general population. We found testicular cancer excess among dizygotic twins (observed/expected [O/E] ratio=1.6, 95 percent confidence interval [CI]=1.0–2.6) that was greater for men younger than 35 years (O/E ratio=2.3, CI=1.1–4.2) compared with older men (O/E ratio = 1.2, CI=0.5–2.4). In addition, a substantially elevated incidence of breast cancer was observed in dizygotic twin women aged 20 to 29 years (O/E=6.7, CI=2.9–13.1). None of the other age or zygosity groups showed notable elevations in incidence of testicular, breast, or other cancers. We conclude that dizygotic twinship may be associated with cancer of the breast and testis among young adults. These findings support the concept that pregnancy hormones are associated with risk of testicular and breast cancer, although non-hormonal aspects of twin pregnancy that vary with respect to zygosity cannot be excluded as explanatory factors.The Swedish Twin Registry is supported by funds from the John D. and Catherine T. MacArthur Foundation.     

No excess of early onset cancer in family members of Wilms tumor patients.

BACKGROUND: Wilms tumor is one of the few pediatric cancers with well-defined familial and genetic components. The authors assessed the risk of early-onset cancers in first- and second-degree relatives of patients enrolled by the National Wilms Tumor Study Group. METHODS: Using a stratified sampling scheme that targeted 530 families of patients who were believed a priori to have a genetic contribution to their disease, the authors conducted interviews regarding cancer occurrence in 4258 family members from 296 families of patients with Wilms tumor. Reports of malignant neoplasms that occurred before 55 years of age were confirmed by review of medical records wherever possible. A period of risk was defined for each family member based on calendar time and his or her relationship to the proband. RESULTS: Ninety-nine cancers were observed, whereas 126.8 were expected by applying standard cancer rates for age and calendar period to the 120,885 person-years at risk. The standardized incidence ratio (SIR) was O-E = 0.78 with 95% confidence interval (CI) of (0.64, 0.95). In subgroup analyses, the highest relative risks were observed for parents of the index case (O/E = 21/13.0 = 1.6, 95% CI = 1.0, 2.5) and for leukemia (O/E = 9/4.9 = 1.9, 95% CI= 0.85,3.5). CONCLUSIONS: The results of this study may provide reassurance to families of children who have had Wilms tumor. Potential sources of bias included the low (56%) rate of participation of targeted families. In general, the biases might have led to the underreporting of some cancers, especially in more distant relatives. The possibility of a slight excess of cancer in parents of Wilms tumor patients could not be excluded.     

Cancer risk in first-degree relatives of children with malignant tumours (province of Trieste,Italy)

We conducted a population-based cohort study in the province of Trieste, Italy, to assess whether the first-degree relatives of children with malignancies had an increased risk of cancer compared with the general population. We examined cancers occurring in all first-degree relatives of children who experienced malignancies under the age of 15 years between 1971 and 1993 (probands). A cohort of the 394 relatives of the 125 probands contributed 7,939 person–years of observation. Among the relatives as a whole, we found a statistically significant increased risk of developing all malignancies except non-melanoma skin carcinoma (21 observed relatives with cancer and 12.46 expected, for a standardized incidence ratio [SIR] of 1.69), of developing breast cancer (SIR = 3.09) and of developing haemolymphatic system neoplasms (SIR = 4.03). This was mainly due to the excess cancer risk in the relatives of probands with intracranial tumours, who showed a significant 3.1-fold risk for developing all cancers but non-melanoma skin tumours. Our findings and the previously reported steep rise in the incidence of childhood brain tumours in our area may imply that not only genetic factors but also shared environmental agents might be involved in the observed aggregation of cancer in the families of probands with intracranial tumours. Int. J. Cancer 73:822–827, 1997. © 1997 Wiley-Liss, Inc.     

Second primary cancers following breast cancer in the Japanese female population.

To assess the risk of developing second primary cancers following breast cancer in Japanese females, we performed a retrospective cohort study of 2786 patients who were newly diagnosed with breast cancer at our hospital between 1970 - 1994, until the end of 1995 (average follow-up period, 8.6 years). The expected number of each second primary cancer was calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar period-specific cancer incidence rates for women obtained from the Osaka Cancer Registry. One hundred and seventeen patients developed a second primary cancer other than subsequent breast cancer, yielding an observed-to-expected ratio (O / E) of 1.3 [95% confidence interval (CI) = 1.1 - 1.6]. The risk for developing a second primary cancer was significantly elevated during the first year following the diagnosis of breast cancer, and decreased with the passage of time to unity. A significantly increased risk was noted for the development of ovarian cancer (O / E = 2.4, 95% CI = 1.0 - 4.6), thyroid cancer (O / E = 3.7, 95% CI = 1.5 - 7.6) and non-Hodgkin's lymphoma (NHL) (O / E = 3.5, 95% CI = 1.4 - 7.1) among the breast cancer patients compared with the general population. Patients who received hormonal therapy as the breast cancer treatment showed a significantly increased risk for ovarian cancer (O / E = 5.5, 95% CI = 1.8 - 12.9). Patients who received chemotherapy as the breast cancer treatment had an increased risk for NHL (O / E = 5.0, 95% CI = 1.6 - 11.6). These findings indicate that Japanese female patients with breast cancer had a 30% higher risk of developing a second primary cancer than the general population, the higher risk being manifested in the early period following the diagnosis of breast cancer. Medical surveillance of breast cancer patients for NHL, as well as for ovarian cancer and thyroid cancer, is required.     

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32) years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1-33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS.     

Second Primary Cancers Following Breast Cancer in the Japanese Female Population

To assess the risk of developing second primary cancers following breast cancer in Japanese females, we performed a retrospective cohort study of 2786 patients who were newly diagnosed with breast cancer at our hospital between 1970-1994, until the end of 1995 (average follow-up period, 8.6 years). The expected number of each second primary cancer was calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar period-specific cancer incidence rates for women obtained from the Osaka Cancer Registry. One hundred and seventeen patients developed a second primary cancer other than subsequent breast cancer, yielding an observed-to-expected ratio (O/E) of 1.3 [95% confidence interval (CI)=1.1-1.6]. The risk for developing a second primary cancer was significantly elevated during the first year following the diagnosis of breast cancer, and decreased with the passage of tune to unity. A significantly increased risk was noted for the development of ovarian cancer (O/E=2.4, 95% CI=1.0-4.6), thyroid cancer (O/E=3.7, 95% CI=1.5-7.6) and non-Hodgkin's lymphoma (NHL) (O/E=3.5, 95% CI=1.4-7.1) among the breast cancer patients compared with the general population. Patients who received hormonal therapy as the breast cancer treatment showed a significantly increased risk for ovarian cancer (O/E=5.5, 95% CI=1.8-12.9). Patients who received chemotherapy as the breast cancer treatment had an increased risk for NHL (O/E=5.0, 95% CI=1.6-11.6). These findings indicate that Japanese female patients with breast cancer had a 30% higher risk of developing a second primary cancer than the general population, the higher risk being manifested in the early period following the diagnosis of breast cancer. Medical surveillance of breast cancer patients for NHL, as well as for ovarian cancer and thyroid cancer, is required.     

Multiple primary cancers in patients with initial laryngeal cancer

The risk of a person developing a second primary cancer was evaluated in 1,215 patients with laryngeal cancer at the National Cancer Center Hospital. Overall, 92 (8.2%) of the male patients and 5 (5.7%) of the female patients developed a second cancer, compared with 83.0 and 3.7, respectively, expected on the basis of general population rates, resulting observed: expected values (O/E) to be 1.1 and 1.3. The numbers of second cancers of the lung (O/E = 1.9), oropharynx (O/E = 8.8) and esophagus (O/E = 2.8) were significantly in excess of those expected, while the number of second stomach cancers (O/E = 0.5) was far below expectation. Synchronous second cancers were significantly higher than expected (O/E = 4.6). Smoking, especially heavy smoking, was related to second lung cancers, but alcohol drinking featured less. Histories of benign respiratory tract and digestive organ diseases were related to second oropharyngeal cancers. Alcohol drinking was related to second stomach cancers. Radiation therapy for the initial laryngeal cancer was related to second oropharyngeal cancers, while hazardous occupations related to noxious agents for respiratory systems featured more prevalently in cases of second lung cancer. Further analytical studies should clarify the roles of smoking, drinking, occupation and various forms of therapy on the risk of developing a different second cancer following laryngeal cancer.     

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.     

Second Primary Cancers Following Non-Hodgkin's Lymphoma in Japan: Increased Risk of Hepatocellular Carcinoma

We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978–1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01–2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E=4.36, 95% CI=1.99–8.28; O =9) and non-lymphocytic leukemia (O/E=26.17, 95% CI=5.26–76.46; O=3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E=5.91, 95% CI =2.70–11.23; O=9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed.     

New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.