- Email: [email protected]
Risk of osteonecrosis in cancer patients
AEP Vol. 14, No. 8 September 2004: 592–624
ABSTRACTS (ACE)
in 2000. Family history was determined through review of a family history questionnaire and reviewed by a genetic counselor for classification. Height and weight 2 years prior were assessed with a self-administered questionnaire. BMI was calculated and categorized according to World Health Organization criteria: low BMI, !18.5 kg/m2; normal, 18.5 to !25 kg/m2; overweight, 25 to !30 kg/m2; and obese, BMI >30 kg/m2. RESULTS: Among men, an overweight or obese BMI was associated with about a 50% increased risk of colorectal cancer relative to men with a normal BMI. The BMI risk for colorectal cancer was attenuated among premenopausal women, and null for postmenopausal women. Increased risk from overweight and obesity were also found among men, but not women, for proximal and distal subsites of colon cancer. Overweight was associated with increased risk of rectal cancer in women only. CONCLUSION: These results suggest that BMI among men and women is differentially associated with colon and rectal cancer risk. Endogenous or exogenous estrogens may, in part, influence this discordance. doi:10.1016/j.annepidem.2004.07.003
P004 RADIOTHERAPY AND GENETIC SUSCEPTIBILITY TO CANCER IN A COHORT OF RETINOBLASTOMA PATIENTS RA Kleinerman, M Stovall, RE Tarone, MA Tucker, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD PURPOSE: Survivors of hereditary retinoblastoma (Rb), a rare childhood cancer of the eye caused by germline mutations of the RB1 tumor suppressor gene, have an elevated risk of developing sarcomas, brain cancer or melanoma, but survivors with nonhereditary Rb, caused by somatic mutations in the RB1 gene, do not appear prone to secondary cancer. Because it is likely that the subsequent cancer risk in hereditary Rb continues throughout adult life, we have been studying a large cohort of Rb survivors to determine their risk of subsequent cancer and to evaluate the contribution of radiation and genetic susceptibility to this risk. METHODS: We extended the follow-up of a cohort of 1601 Rb survivors, diagnosed from 1914 to 1984 at two medical centers, to identify their risk of new cancers through 2000, compared with the expected number of cancers estimated from age-, sex-, and calendar year-specific from the Connecticut Tumor Registry. RESULTS: Subsequent cancer risk in 963 hereditary Rb patients (standardized incidence ratio SIR Z 19, 95% confidence interval CI Z 16–21) exceeded the risk in 638 sporadic RB patients (SIR Z 1.2, 95% CI Z 0.7–2.0). For hereditary Rb, the SIR was higher for those treated with radiation (SIR Z 22, 95% CI Z 19–24) versus those who were not (SIR Z 6.9, 95% CI Z 4.1–11). Among the hereditary Rb patients, significantly increased risks for cancers of the bone, soft tissue, brain, nasal cavities, and eye or orbit were likely related to radiation, which is consistent with previous findings. Newly identified risks possibly linked to radiation included cancers of the salivary gland, tongue, and breast. Excess risks for melanoma, and cancers of the lung, colon, and uterus in hereditary patients were unlikely to be associated with radiation in this cohort.
593
CONCLUSION: These data reveal a continuing increased cancer risk in hereditary but not nonhereditary Rb. Radiotherapy for hereditary Rb in early childhood continues to be associated with cancers in adulthood. doi:10.1016/j.annepidem.2004.07.004
P005S RISK OF LUNG CANCER FROM EXPOSURE TO DUSTS AND FIBERS IN LENINGRAD PROVINCE, RUSSIA A Baccarelli, M Tretiakova, S Gorbanev, A Lomtev, I Klimkina, V Tchibissov, O Averkina, C Rice, M Dosemeci, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD PURPOSE: Several dusts and fibers have been classified by the International Agency for Research on Cancer (IARC) as carcinogens to humans. Others have been indicated as risk factors for lung cancer, but with no conclusive demonstration. We conducted an autopsy-based case–control study in Leningrad Province, Russia, to investigate the association of lung cancer risk with the exposure to 58 different dusts and fibers. METHODS: We identified 540 pathologically diagnosed lung cancer cases (474 males, 66 females) and 582 controls (453 males, 129 females) among subjects who had died in hospitals of Leningrad Province between 1993 and 1998. We retrieved subject-specific quantitative measurements of 15 organic, 15 synthetic and 28 natural inorganic dusts and fibers performed since 1950 in each work facility of the study area. We used unconditional logistic regression to compute sex-specific odds ratios (OR) and 95% confidence intervals (CI) for lung cancer adjusted for age, smoking, and residence. RESULTS: Nearly 90% of the study subjects had been exposed to one or more of the 58 dusts and fibers evaluated. Exposure above the specific maximum allowable concentrations (MACs) was frequent in this population, with average exposure intensity higher than MACs for 16% of the subjects. In males, lung cancer risk was increased among workers exposed to linen dust (OR Z 3.68, 95% CI Z 1.00–13.6) or unspecified dusts and fibers (OR Z 1.44, 95% CI Z 1.07–1.94). A nonsignificant increased risk, correlated with exposure intensity, was observed in males exposed to synthetic vitreous fibers (OR Z 1.82, 95% CI Z 0.88–3.75). Male subjects exposed to quartz dust had OR Z 1.27 (95% CI Z 0.83–1.93). In female subjects, a nonsignificant excess risk, which tended to increase with cumulative exposure, was observed for paper dust (OR Z 1.77, 95% CI Z 0.74–4.20) and for unspecified dusts and fibers (OR Z 1.52, 95% CI Z 0.77–3.03). CONCLUSION: Most study subjects were exposed to dusts and fibers, often above the maximum allowable concentrations. We observed increased lung cancer risks for specific categories of dusts and fibers. doi:10.1016/j.annepidem.2004.07.005
P006 RISK OF OSTEONECROSIS IN CANCER PATIENTS MK Balcewicz-Sablin´ska, A Gonza´les-Pe´rez, LA Garcia Rodrı´guez, Clinical Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland
594
ABSTRACTS (ACE)
AEP Vol. 14, No. 8 September 2004 : 592–624
PURPOSE: Osteonecrosis (ON) has been described in cancer patients in association with cancer and its treatment using radiotherapy or chemotherapy with and without corticosteroids; however, epidemiologic data on the overall risk of ON in cancer patients are quite limited. The purpose of this population-based cohort study was to estimate risk of ON in cancer patients. METHODS: A source population of 5,597,148 persons (8,998, 314 person-years) aged 20 to 84 years with information recorded in the UK General Practice Research Database (GPRD) during the period January 1, 1994, to December 31, 2001, was identified as the general population cohort. From this cohort, two additional cohorts were drawn: a cohort of cancer patients (106,477 personyears) and a cohort of cancer-free patients (8,611,725 personyears). Diagnostic codes indicative or suggestive of ON were defined. All members in the two cohorts were followed-up until the earliest of the following endpoints: (i) diagnosis of ON; (ii) death; or (iii) end of the study period. Cancer treatment was not assessed. Incidence rates of ON (all sites) in the two cohorts and the age- and sex-adjusted relative risk of ON for the cancer patients were calculated. RESULTS: The estimated incidence rate of ON among the cancer cohort was 1.32 per 10,000 person-years (95% CI Z 0.75– 2.15). In the cancer-free population, the incidence rate was estimated to be 0.28 per 10,000 person-years (95% CI Z 0.25– 0.31). Compared with the risk among the cancer-free cohort, the age- and sex-adjusted relative risk for ON in cancer patients was 3.38 (95% CI Z 1.95–5.84, P ! 0.0005). CONCLUSION: Compared with a cancer-free population, cancer patients are estimated to be 3.4 times more likely to develop ON. These preliminary data suggest that with increasing survival of cancer patients, health care providers and patients need to be aware of ON as a potential factor in comorbidity. doi:10.1016/j.annepidem.2004.07.006
P007 ORGANOCHLORINE COMPOUNDS IN CARPET DUST AND NON-HODGKIN LYMPHOMA RISK JS Colt, RK Severson, J Lubin, N Rothman, D Camann, S Davis, J Cerhan, W Cozen, P Hartge, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD PURPOSE: The incidence of non-Hodgkin lymphoma (NHL) has risen over the past several decades, and a substantial portion of the increase remains unexplained. In this population-based case– control study in Iowa and metropolitan Detroit, Los Angeles, and Seattle, we examined NHL risk and exposure to organochlorine compounds using concentrations measured in household carpet dust as an exposure indicator. METHODS: We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among residents aged 20 to 74 and selected controls using random-digit-dialing and Medicare eligibility files. Used vacuum bags were collected from participants who had owned at least half of their carpets for at least 5 years. The current analysis is based on dust samples from 603 Caucasian cases and 443 Caucasian controls. RESULTS: Age of the home was a significant predictor of organochlorine levels in carpet dust, with the highest concentrations found in homes built before 1960 and the lowest in homes built after 1980. There was a statistically significant elevation in
NHL risk if DDE (metabolite of DDT) was detected in the dust (odds ratio OR Z 1.3, 95% confidence interval CI Z 1.0–1.7) or if at least one of the five polychlorinated biphenyl congeners (PCB 105, PCB 138, PCB 153, PCB 170, PCB 180) was detected (OR Z 1.5, 95% CI Z 1.2–2.0). When levels above the detection limit were divided into tertiles, risk was significantly elevated in the top tertiles of DDE and PCB 180, and in the top two tertiles of total PCBs. There were significant positive trends in risk with increasing concentrations of DDE and PCB 180 (Ptrend Z 0.02 and 0.03, respectively), but not for total PCBs. CONCLUSION: Our data suggest an increased risk of NHL from exposure to DDE and PCB 180. Previous studies using other approaches have had inconsistent findings. Additional studies are needed to evaluate how well carpet dust represents historic exposure to organochlorine compounds. Results from blood samples of study participants may help to clarify the relationship between organochlorine exposure and NHL risk. doi:10.1016/j.annepidem.2004.07.007
P008 NUTRITIONAL CORRELATES OF BIOELECTRICAL IMPEDANCE PHASE ANGLE IN COLORECTAL CANCER D Gupta, CA Lammersfeld, PG Vashi, JL Burrows, S Dahlk, S Hoffman, CG Lis, JF Grutsch, Office of Research, Cancer Treatment Centers of AmericaÒ at Midwestern Regional Medical Center, Zion, IL, and Department of Epidemiology and Biostatistics, University of Illinois School of Public Health, Chicago IL PURPOSE: Malnutrition is a strong predictor of morbidity and mortality in advanced cancer. Accurate assessment of malnutrition is a challenge in these patients. Bioelectrical impedance analysis (BIA) is a safe, simple, noninvasive and objective technique that is increasingly being used to evaluate nutritional status and changes in body composition in cancer patients. BIA measures resistance and reactance to the flow of a constant alternating electric current through a living organism, which in turn is used to calculate phase angle, a measure of cellular health and integrity. The purpose of this study was to investigate the relationship between BIA-derived phase angle and commonly used indicators of nutritional status. METHODS: A case series of 81 histologically confirmed stage III– IV colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between January 2000 and March 2003 were included in the study. The correlations between phase angle and serum albumin, prealbumin, transferrin, and subjective global assessment (SGA) were studied using Spearman’s correlation coefficient, due to the nonnormal distributions of these variables. RESULTS: We found a modest positive correlation between phase angle and albumin (r Z 0.29; P Z 0.01); the higher the phase angle, the greater the albumin levels and better the nutritional status. As expected, we also found a modest negative correlation between phase angle and SGA score (r Z ÿ0.29; P Z 0.01); the higher the phase angle, the lower the SGA scores, suggesting better nourishment. No statistically significant correlations were found between phase angle and prealbumin (r Z 0.06; P Z 0.61) and transferrin (r Z 0.17; P Z 0.15).
ABSTRACTS (ACE)
in 2000. Family history was determined through review of a family history questionnaire and reviewed by a genetic counselor for classification. Height and weight 2 years prior were assessed with a self-administered questionnaire. BMI was calculated and categorized according to World Health Organization criteria: low BMI, !18.5 kg/m2; normal, 18.5 to !25 kg/m2; overweight, 25 to !30 kg/m2; and obese, BMI >30 kg/m2. RESULTS: Among men, an overweight or obese BMI was associated with about a 50% increased risk of colorectal cancer relative to men with a normal BMI. The BMI risk for colorectal cancer was attenuated among premenopausal women, and null for postmenopausal women. Increased risk from overweight and obesity were also found among men, but not women, for proximal and distal subsites of colon cancer. Overweight was associated with increased risk of rectal cancer in women only. CONCLUSION: These results suggest that BMI among men and women is differentially associated with colon and rectal cancer risk. Endogenous or exogenous estrogens may, in part, influence this discordance. doi:10.1016/j.annepidem.2004.07.003
P004 RADIOTHERAPY AND GENETIC SUSCEPTIBILITY TO CANCER IN A COHORT OF RETINOBLASTOMA PATIENTS RA Kleinerman, M Stovall, RE Tarone, MA Tucker, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD PURPOSE: Survivors of hereditary retinoblastoma (Rb), a rare childhood cancer of the eye caused by germline mutations of the RB1 tumor suppressor gene, have an elevated risk of developing sarcomas, brain cancer or melanoma, but survivors with nonhereditary Rb, caused by somatic mutations in the RB1 gene, do not appear prone to secondary cancer. Because it is likely that the subsequent cancer risk in hereditary Rb continues throughout adult life, we have been studying a large cohort of Rb survivors to determine their risk of subsequent cancer and to evaluate the contribution of radiation and genetic susceptibility to this risk. METHODS: We extended the follow-up of a cohort of 1601 Rb survivors, diagnosed from 1914 to 1984 at two medical centers, to identify their risk of new cancers through 2000, compared with the expected number of cancers estimated from age-, sex-, and calendar year-specific from the Connecticut Tumor Registry. RESULTS: Subsequent cancer risk in 963 hereditary Rb patients (standardized incidence ratio SIR Z 19, 95% confidence interval CI Z 16–21) exceeded the risk in 638 sporadic RB patients (SIR Z 1.2, 95% CI Z 0.7–2.0). For hereditary Rb, the SIR was higher for those treated with radiation (SIR Z 22, 95% CI Z 19–24) versus those who were not (SIR Z 6.9, 95% CI Z 4.1–11). Among the hereditary Rb patients, significantly increased risks for cancers of the bone, soft tissue, brain, nasal cavities, and eye or orbit were likely related to radiation, which is consistent with previous findings. Newly identified risks possibly linked to radiation included cancers of the salivary gland, tongue, and breast. Excess risks for melanoma, and cancers of the lung, colon, and uterus in hereditary patients were unlikely to be associated with radiation in this cohort.
593
CONCLUSION: These data reveal a continuing increased cancer risk in hereditary but not nonhereditary Rb. Radiotherapy for hereditary Rb in early childhood continues to be associated with cancers in adulthood. doi:10.1016/j.annepidem.2004.07.004
P005S RISK OF LUNG CANCER FROM EXPOSURE TO DUSTS AND FIBERS IN LENINGRAD PROVINCE, RUSSIA A Baccarelli, M Tretiakova, S Gorbanev, A Lomtev, I Klimkina, V Tchibissov, O Averkina, C Rice, M Dosemeci, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD PURPOSE: Several dusts and fibers have been classified by the International Agency for Research on Cancer (IARC) as carcinogens to humans. Others have been indicated as risk factors for lung cancer, but with no conclusive demonstration. We conducted an autopsy-based case–control study in Leningrad Province, Russia, to investigate the association of lung cancer risk with the exposure to 58 different dusts and fibers. METHODS: We identified 540 pathologically diagnosed lung cancer cases (474 males, 66 females) and 582 controls (453 males, 129 females) among subjects who had died in hospitals of Leningrad Province between 1993 and 1998. We retrieved subject-specific quantitative measurements of 15 organic, 15 synthetic and 28 natural inorganic dusts and fibers performed since 1950 in each work facility of the study area. We used unconditional logistic regression to compute sex-specific odds ratios (OR) and 95% confidence intervals (CI) for lung cancer adjusted for age, smoking, and residence. RESULTS: Nearly 90% of the study subjects had been exposed to one or more of the 58 dusts and fibers evaluated. Exposure above the specific maximum allowable concentrations (MACs) was frequent in this population, with average exposure intensity higher than MACs for 16% of the subjects. In males, lung cancer risk was increased among workers exposed to linen dust (OR Z 3.68, 95% CI Z 1.00–13.6) or unspecified dusts and fibers (OR Z 1.44, 95% CI Z 1.07–1.94). A nonsignificant increased risk, correlated with exposure intensity, was observed in males exposed to synthetic vitreous fibers (OR Z 1.82, 95% CI Z 0.88–3.75). Male subjects exposed to quartz dust had OR Z 1.27 (95% CI Z 0.83–1.93). In female subjects, a nonsignificant excess risk, which tended to increase with cumulative exposure, was observed for paper dust (OR Z 1.77, 95% CI Z 0.74–4.20) and for unspecified dusts and fibers (OR Z 1.52, 95% CI Z 0.77–3.03). CONCLUSION: Most study subjects were exposed to dusts and fibers, often above the maximum allowable concentrations. We observed increased lung cancer risks for specific categories of dusts and fibers. doi:10.1016/j.annepidem.2004.07.005
P006 RISK OF OSTEONECROSIS IN CANCER PATIENTS MK Balcewicz-Sablin´ska, A Gonza´les-Pe´rez, LA Garcia Rodrı´guez, Clinical Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland
594
ABSTRACTS (ACE)
AEP Vol. 14, No. 8 September 2004 : 592–624
PURPOSE: Osteonecrosis (ON) has been described in cancer patients in association with cancer and its treatment using radiotherapy or chemotherapy with and without corticosteroids; however, epidemiologic data on the overall risk of ON in cancer patients are quite limited. The purpose of this population-based cohort study was to estimate risk of ON in cancer patients. METHODS: A source population of 5,597,148 persons (8,998, 314 person-years) aged 20 to 84 years with information recorded in the UK General Practice Research Database (GPRD) during the period January 1, 1994, to December 31, 2001, was identified as the general population cohort. From this cohort, two additional cohorts were drawn: a cohort of cancer patients (106,477 personyears) and a cohort of cancer-free patients (8,611,725 personyears). Diagnostic codes indicative or suggestive of ON were defined. All members in the two cohorts were followed-up until the earliest of the following endpoints: (i) diagnosis of ON; (ii) death; or (iii) end of the study period. Cancer treatment was not assessed. Incidence rates of ON (all sites) in the two cohorts and the age- and sex-adjusted relative risk of ON for the cancer patients were calculated. RESULTS: The estimated incidence rate of ON among the cancer cohort was 1.32 per 10,000 person-years (95% CI Z 0.75– 2.15). In the cancer-free population, the incidence rate was estimated to be 0.28 per 10,000 person-years (95% CI Z 0.25– 0.31). Compared with the risk among the cancer-free cohort, the age- and sex-adjusted relative risk for ON in cancer patients was 3.38 (95% CI Z 1.95–5.84, P ! 0.0005). CONCLUSION: Compared with a cancer-free population, cancer patients are estimated to be 3.4 times more likely to develop ON. These preliminary data suggest that with increasing survival of cancer patients, health care providers and patients need to be aware of ON as a potential factor in comorbidity. doi:10.1016/j.annepidem.2004.07.006
P007 ORGANOCHLORINE COMPOUNDS IN CARPET DUST AND NON-HODGKIN LYMPHOMA RISK JS Colt, RK Severson, J Lubin, N Rothman, D Camann, S Davis, J Cerhan, W Cozen, P Hartge, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD PURPOSE: The incidence of non-Hodgkin lymphoma (NHL) has risen over the past several decades, and a substantial portion of the increase remains unexplained. In this population-based case– control study in Iowa and metropolitan Detroit, Los Angeles, and Seattle, we examined NHL risk and exposure to organochlorine compounds using concentrations measured in household carpet dust as an exposure indicator. METHODS: We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among residents aged 20 to 74 and selected controls using random-digit-dialing and Medicare eligibility files. Used vacuum bags were collected from participants who had owned at least half of their carpets for at least 5 years. The current analysis is based on dust samples from 603 Caucasian cases and 443 Caucasian controls. RESULTS: Age of the home was a significant predictor of organochlorine levels in carpet dust, with the highest concentrations found in homes built before 1960 and the lowest in homes built after 1980. There was a statistically significant elevation in
NHL risk if DDE (metabolite of DDT) was detected in the dust (odds ratio OR Z 1.3, 95% confidence interval CI Z 1.0–1.7) or if at least one of the five polychlorinated biphenyl congeners (PCB 105, PCB 138, PCB 153, PCB 170, PCB 180) was detected (OR Z 1.5, 95% CI Z 1.2–2.0). When levels above the detection limit were divided into tertiles, risk was significantly elevated in the top tertiles of DDE and PCB 180, and in the top two tertiles of total PCBs. There were significant positive trends in risk with increasing concentrations of DDE and PCB 180 (Ptrend Z 0.02 and 0.03, respectively), but not for total PCBs. CONCLUSION: Our data suggest an increased risk of NHL from exposure to DDE and PCB 180. Previous studies using other approaches have had inconsistent findings. Additional studies are needed to evaluate how well carpet dust represents historic exposure to organochlorine compounds. Results from blood samples of study participants may help to clarify the relationship between organochlorine exposure and NHL risk. doi:10.1016/j.annepidem.2004.07.007
P008 NUTRITIONAL CORRELATES OF BIOELECTRICAL IMPEDANCE PHASE ANGLE IN COLORECTAL CANCER D Gupta, CA Lammersfeld, PG Vashi, JL Burrows, S Dahlk, S Hoffman, CG Lis, JF Grutsch, Office of Research, Cancer Treatment Centers of AmericaÒ at Midwestern Regional Medical Center, Zion, IL, and Department of Epidemiology and Biostatistics, University of Illinois School of Public Health, Chicago IL PURPOSE: Malnutrition is a strong predictor of morbidity and mortality in advanced cancer. Accurate assessment of malnutrition is a challenge in these patients. Bioelectrical impedance analysis (BIA) is a safe, simple, noninvasive and objective technique that is increasingly being used to evaluate nutritional status and changes in body composition in cancer patients. BIA measures resistance and reactance to the flow of a constant alternating electric current through a living organism, which in turn is used to calculate phase angle, a measure of cellular health and integrity. The purpose of this study was to investigate the relationship between BIA-derived phase angle and commonly used indicators of nutritional status. METHODS: A case series of 81 histologically confirmed stage III– IV colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between January 2000 and March 2003 were included in the study. The correlations between phase angle and serum albumin, prealbumin, transferrin, and subjective global assessment (SGA) were studied using Spearman’s correlation coefficient, due to the nonnormal distributions of these variables. RESULTS: We found a modest positive correlation between phase angle and albumin (r Z 0.29; P Z 0.01); the higher the phase angle, the greater the albumin levels and better the nutritional status. As expected, we also found a modest negative correlation between phase angle and SGA score (r Z ÿ0.29; P Z 0.01); the higher the phase angle, the lower the SGA scores, suggesting better nourishment. No statistically significant correlations were found between phase angle and prealbumin (r Z 0.06; P Z 0.61) and transferrin (r Z 0.17; P Z 0.15).