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Alcohol drinking, tobacco smoking, LIG1 polymorphisms and head and neck cancers risk
AEP Vol. 15, No. 8 September 2005: 630–665
patterns in people aged 40 and older, incidence rates in those aged 20–39 years and younger increased during the study period. While the results from Poisson regression analyses suggest overall significant trends of declining incidence rates in cervical cancer, there seemed to be a small upward tail toward the end of the study period. CONCLUSION: The findings also indicated two worrisome aspects. First, the incidence rates seemed to increase in younger women; second, there seemed to be a rebound in incidence rates toward the end of the study period. The findings highlight the importance of targeted education toward high-risk population and shed light toward setting up more efficient screening strategies.
P04 CANCER INCIDENCE IN WOMEN EXPOSED TO DES IN UTERO R Troisi, JR Palmer, M Hyer, R Hoover, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, Slone Epidemiology Unit, Boston University, Boston, MA, IMS, Rockville, MD PURPOSE: Diethylstilbestrol (DES), a synthetic estrogen administered to millions of women in the U.S. and Europe, was shown in the early 1970s to have a strong association with clear cell adenocarcinoma (CCA) in the daughters who were exposed in utero. Results from data collected through 1994 from the NCI DES Combined Cohorts Follow-up Study showed that DES-exposed daughters experienced no excess risk of all cancers combined in comparisons with both the general population and daughters who were unexposed to DES. Except for CCA, for which a strong association was demonstrated, risk in exposed daughters was not elevated for individual cancer sites. Data through 1997 suggested, however, that DES is associated with an elevated breast cancer risk in women 40 years of age and older. METHODS: Preliminary analysis of new cases reported through 2001 compared observed to expected cancer rates based upon ageand calendar-year specific SEER incidence rates in white females. Standardized incidence ratios (SIR) with 95% confidence intervals were calculated. RESULTS: A total of 235 cancer cases occurred during follow up, with 175 occurring among exposed women (97,830 person-years) and 60 among unexposed women (34,810). Overall, there was no excess risk of cancer among DES-exposed daughters for all cancers combined (SIR 1.1; 95% CI 0.91–1.2), or among the unexposed comparison group (SIR 0.86; 95% CI 0.67–1.1). One new case of CCA of the cervix/vagina occurred since the 1994 follow up for a total of four confirmed cases of CCA in the exposed with less than 0.1 expected resulting in a SIR of 41 (95% CI 15–110), and no cases occurring in the unexposed women. CONCLUSIONS: Data addressing the association of DES and cancer risk in daughters updated with 7 additional years of followup will be presented. Specific results for cancer sites will be discussed in the context of the in utero estrogen exposure hypothesis and subsequent cancer risk.
ABSTRACTS (ACE)
631
P05 THYROID CARCINOMA INCIDENCE AND MORTALITY ANALYSIS DURING 1981–2001 IN TIANJIN, CHINA BY Qian, KX Chen, M He, SF Dong, DM Han, L Lei PURPOSE: To describe the long-term incidence and mortality trends of thyroid carcinoma and relate them to potential risk factors. METHODS: All of the cases were from The Tianjin Cancer Registry. Numbers in each age-sex specific population for the six urban districts were obtained from the Tianjin Police Head Office. Descriptive epidemiological methods were used to study the incidence rates of thyroid cancer. Age-sex specific incidence rates were calculated and plotted. The incidence and mortality rate was compared from 1981 to 2001 using the c2 trend test. The average incidence rate and mortality was compared using the c2 test. Age at diagnosis was compared with t-test. All statistical analyses were carried out using SAS 8.1 for windows. RESULTS: A total of 1,318 cases from thyroid cancer were identified in Tianjin between 1981 and 2001, 352 males and 966 females respectively. The incidence rates have increased from 0.87/ 100,000 in 1981 to 2.54/100,000 in 2001, up 193%. Females had consistently higher incidence rates than males across all age groups during this period (c2 Z 294.429, p ! 0.001). While the observed incidence increases were significant in both males and females, the magnitude of incidence increase was greater in females with the incidence ratios between males and females changing from 1:2.7 in 1981 to 1:4.6 in 2001. The results also suggest age-gender interactions. Male incidence rates increased gradually with increasing age and peeked around 60 years of age. However, the incidence rates in females climbed steeply after age 25 and reached its highest in the 3550 ages. The average mortality rate was 0.37/ 100,000. The mortality rates were also found to be higher in older age groups in both females and males. Although the incidence trend increased with time, the mortality trend changed a little. CONCLUSION: The significant increase in thyroid carcinoma incidence during the last 21 years reported in this study suggests that changes in environmental factors may have played an important role. Further epidemiological investigations are warranted.
P06 ALCOHOL DRINKING, TOBACCO SMOKING, LIG1 POLYMORPHISMS AND HEAD AND NECK CANCERS RISK YA Lee1, M Hashibe2, NY You1, W Cao1, S Greenland1, DP Tashkin3, W Cozen4, TM Mack4, H Morgenstern5, ZF Zhang1, 1UCLA School of Public Health, Los Angeles, CA 90095, USA, 2IARC, Lyon, France, 3UCLA School of Medicine, 4 USC School of Medicine, 5Dept. of Epidemiology, University of Michigan PURPOSE: Alcohol and tobacco are known to be associated with the development of head and neck cancers, including oralpharyngeal, laryngeal and esophageal cancers. LIG1 is involved in DNA replication and for sealing single-strand breaks; thus, it plays
632
ABSTRACTS (ACE)
an important role in nucleotide excision repair (NER) and longpatch base-excision repair (BER). The A / C polymorphism in exon 6 might affect the transcription and/or translation and consequently influence the DNA repair capacity. The objectives of this study were to evaluate the associations between the polymorphisms of LIG1 and the head and neck cancers risk, and to investigate the potential interactions between the polymorphisms and the environmental factors. METHODS: This study was a population-based case-control study with 601 head and neck cancer cases and 1040 population controls in Los Angeles County. Epidemiological data were collected by face-to-face interviews using a standard questionnaire. Laboratory analysis on the genetic polymorphisms of LIG1 was performed with PCR-RFLP. Unconditional logistic regression model was employed in data analysis. RESULTS: The results showed an OR Z 1.1 (95% CI 0.8 – 1.5) for AA vs. AC and CC, adjusting for age, sex, alcohol drinking and tobacco smoking. In addition, the joint effect analysis showed an adjusted OR of 7.5 (95% CI 3.0 – 18.3) for those who drank more than 25 alcohol/day)years, smoked more than 40 pack-years and were with AA LIG1 genotype (versus less than 25 alcohol/ day)years, less than 40 pack-years and with AC/CC LIG1 genotype). CONCLUSION: The analysis suggested there was weak evidence of the association between LIG1 polymorphisms and head and neck cancers risk. Nonetheless, the results implied a strong modifying effect of both the alcohol and tobacco combined for the effect of LIG1 polymorphisms on the risk of head and neck cancers.
P07 ASSESSING ACTIVITIES ASSOCIATED WITH TIME SPENT OUTDOORS IN AN OCCUPATIONAL COHORT OF RADIOLOGIC TECHNOLOGISTS RK Kwok1, T Fears2, RA Kleinerman2, DM Freedman2, BH Alexander3, D Kampa3, RE Johnson1, MS Linet2, 1 RTI International, Research Triangle Park, NC, 2Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, 3Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN PURPOSE: To identify key daily activities in which persons working as radiologic technologists spend the majority of time outdoors. The findings will be used to design improved questionnaires to estimate retrospective UV exposure for future casecontrol studies of skin cancer and other malignancies to be undertaken within a large cohort of these medical radiation workers. METHODS: We evaluated the self-reported activities undertaken during time spent outdoors between 9 AM and 5 PM for 125 individuals (ages 40–59 and 60+ years old) who filled out a 7–day daily activity diary in September 2004. Daily UV measurements were also recorded for each individual. We initially classified activities into 37 groupings of similar activities before determining the 7 activities that accounted for the majority of time spent outdoors. We evaluated differences by age, gender, and geographic location of the individual in addition to whether these activities were carried out on a weekday or weekend day.
AEP Vol. 15, No. 8 September 2005: 630–665
RESULTS: Of a possible 13,953 daily diary entries, we ascertained that 4697 entries (totaling 1408 hours) were associated with time spent outdoors. The 7 major categories, which accounted for over 93% of the total time spent outdoors, included driving, yard work, home maintenance, walking or doing errands, recreational activities or sports, water activities, and leisure activities or relaxing outside. Differences in time spent outdoors were noted for age, gender, and weekend versus weekday. CONCLUSION: The results of this analysis, in conjunction with UV measurements, will be useful in developing questionnaires that more accurately estimate UV exposure in relation to cancer risks in future case-control studies.
P08 A META-ANALYSIS OF OCCUPATIONAL TRICHLOROETHYLENE EXPOSURE AND SELECTED CANCERS MA Kelsh1, M Weingart1, JH Mandel1, PJ Mink1, DD Alexander1, R Basu1, M Goodman2, 1Exponent, Inc., Menlo Park, CA, Oakland, CA; Chicago, IL; Washington, DC, 2Rollins School of Public Health, Emory University, Atlanta, GA PURPOSE: This review and meta-analysis evaluated occupational studies of TCE exposure and leukemia, non-Hodgkin’s lymphoma (NHL), and cancers of the lung, kidney, liver, and esophagus. METHODS: We summarized findings among occupational cohort studies and case-control studies that attempted to specifically identify and characterize TCE exposure. We identified 25 epidemiologic studies that met our inclusion criteria (17 cohort studies, 8 case-control studies). Cohort studies were categorized into ‘‘Group 1’’ and ‘‘Group 2’’ studies by type of exposure information available. RESULTS: The meta-analysis relative risk estimates (mRR) for kidney cancer suggested homogeneity of findings across studies in the Group 1 category (p value Z 0.97) with similar findings among U.S., European, and Aerospace/Aircraft studies. For liver cancer, mRR estimates varied. Aerospace/aircraft workers and Group 2 studies showed no association, whereas across European studies the mRR was slightly elevated. The findings for NHL indicated significant heterogeneity with lower mRRs among United States and aerospace/aircraft worker studies compared to a higher mRR for the European studies. Findings for esophageal cancer across studies were also heterogeneous. Similar to liver cancer and NHL, a pattern of higher mRRs was noted among European studies compared to other subgroups. CONCLUSION: This meta-analysis of occupational TCE exposure and NHL, leukemia, and cancers of the kidney, liver, esophagus, and lung showed no associations with lung and leukemia and inconsistent associations for kidney, liver, NHL and esophageal cancers across the Group 1 cohort studies considered as more informative. Heterogeneity of findings, limitations in exposure assessment and exposure comparability, and differences in disease classification limit interpretation of the epidemiologic data.
patterns in people aged 40 and older, incidence rates in those aged 20–39 years and younger increased during the study period. While the results from Poisson regression analyses suggest overall significant trends of declining incidence rates in cervical cancer, there seemed to be a small upward tail toward the end of the study period. CONCLUSION: The findings also indicated two worrisome aspects. First, the incidence rates seemed to increase in younger women; second, there seemed to be a rebound in incidence rates toward the end of the study period. The findings highlight the importance of targeted education toward high-risk population and shed light toward setting up more efficient screening strategies.
P04 CANCER INCIDENCE IN WOMEN EXPOSED TO DES IN UTERO R Troisi, JR Palmer, M Hyer, R Hoover, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, Slone Epidemiology Unit, Boston University, Boston, MA, IMS, Rockville, MD PURPOSE: Diethylstilbestrol (DES), a synthetic estrogen administered to millions of women in the U.S. and Europe, was shown in the early 1970s to have a strong association with clear cell adenocarcinoma (CCA) in the daughters who were exposed in utero. Results from data collected through 1994 from the NCI DES Combined Cohorts Follow-up Study showed that DES-exposed daughters experienced no excess risk of all cancers combined in comparisons with both the general population and daughters who were unexposed to DES. Except for CCA, for which a strong association was demonstrated, risk in exposed daughters was not elevated for individual cancer sites. Data through 1997 suggested, however, that DES is associated with an elevated breast cancer risk in women 40 years of age and older. METHODS: Preliminary analysis of new cases reported through 2001 compared observed to expected cancer rates based upon ageand calendar-year specific SEER incidence rates in white females. Standardized incidence ratios (SIR) with 95% confidence intervals were calculated. RESULTS: A total of 235 cancer cases occurred during follow up, with 175 occurring among exposed women (97,830 person-years) and 60 among unexposed women (34,810). Overall, there was no excess risk of cancer among DES-exposed daughters for all cancers combined (SIR 1.1; 95% CI 0.91–1.2), or among the unexposed comparison group (SIR 0.86; 95% CI 0.67–1.1). One new case of CCA of the cervix/vagina occurred since the 1994 follow up for a total of four confirmed cases of CCA in the exposed with less than 0.1 expected resulting in a SIR of 41 (95% CI 15–110), and no cases occurring in the unexposed women. CONCLUSIONS: Data addressing the association of DES and cancer risk in daughters updated with 7 additional years of followup will be presented. Specific results for cancer sites will be discussed in the context of the in utero estrogen exposure hypothesis and subsequent cancer risk.
ABSTRACTS (ACE)
631
P05 THYROID CARCINOMA INCIDENCE AND MORTALITY ANALYSIS DURING 1981–2001 IN TIANJIN, CHINA BY Qian, KX Chen, M He, SF Dong, DM Han, L Lei PURPOSE: To describe the long-term incidence and mortality trends of thyroid carcinoma and relate them to potential risk factors. METHODS: All of the cases were from The Tianjin Cancer Registry. Numbers in each age-sex specific population for the six urban districts were obtained from the Tianjin Police Head Office. Descriptive epidemiological methods were used to study the incidence rates of thyroid cancer. Age-sex specific incidence rates were calculated and plotted. The incidence and mortality rate was compared from 1981 to 2001 using the c2 trend test. The average incidence rate and mortality was compared using the c2 test. Age at diagnosis was compared with t-test. All statistical analyses were carried out using SAS 8.1 for windows. RESULTS: A total of 1,318 cases from thyroid cancer were identified in Tianjin between 1981 and 2001, 352 males and 966 females respectively. The incidence rates have increased from 0.87/ 100,000 in 1981 to 2.54/100,000 in 2001, up 193%. Females had consistently higher incidence rates than males across all age groups during this period (c2 Z 294.429, p ! 0.001). While the observed incidence increases were significant in both males and females, the magnitude of incidence increase was greater in females with the incidence ratios between males and females changing from 1:2.7 in 1981 to 1:4.6 in 2001. The results also suggest age-gender interactions. Male incidence rates increased gradually with increasing age and peeked around 60 years of age. However, the incidence rates in females climbed steeply after age 25 and reached its highest in the 3550 ages. The average mortality rate was 0.37/ 100,000. The mortality rates were also found to be higher in older age groups in both females and males. Although the incidence trend increased with time, the mortality trend changed a little. CONCLUSION: The significant increase in thyroid carcinoma incidence during the last 21 years reported in this study suggests that changes in environmental factors may have played an important role. Further epidemiological investigations are warranted.
P06 ALCOHOL DRINKING, TOBACCO SMOKING, LIG1 POLYMORPHISMS AND HEAD AND NECK CANCERS RISK YA Lee1, M Hashibe2, NY You1, W Cao1, S Greenland1, DP Tashkin3, W Cozen4, TM Mack4, H Morgenstern5, ZF Zhang1, 1UCLA School of Public Health, Los Angeles, CA 90095, USA, 2IARC, Lyon, France, 3UCLA School of Medicine, 4 USC School of Medicine, 5Dept. of Epidemiology, University of Michigan PURPOSE: Alcohol and tobacco are known to be associated with the development of head and neck cancers, including oralpharyngeal, laryngeal and esophageal cancers. LIG1 is involved in DNA replication and for sealing single-strand breaks; thus, it plays
632
ABSTRACTS (ACE)
an important role in nucleotide excision repair (NER) and longpatch base-excision repair (BER). The A / C polymorphism in exon 6 might affect the transcription and/or translation and consequently influence the DNA repair capacity. The objectives of this study were to evaluate the associations between the polymorphisms of LIG1 and the head and neck cancers risk, and to investigate the potential interactions between the polymorphisms and the environmental factors. METHODS: This study was a population-based case-control study with 601 head and neck cancer cases and 1040 population controls in Los Angeles County. Epidemiological data were collected by face-to-face interviews using a standard questionnaire. Laboratory analysis on the genetic polymorphisms of LIG1 was performed with PCR-RFLP. Unconditional logistic regression model was employed in data analysis. RESULTS: The results showed an OR Z 1.1 (95% CI 0.8 – 1.5) for AA vs. AC and CC, adjusting for age, sex, alcohol drinking and tobacco smoking. In addition, the joint effect analysis showed an adjusted OR of 7.5 (95% CI 3.0 – 18.3) for those who drank more than 25 alcohol/day)years, smoked more than 40 pack-years and were with AA LIG1 genotype (versus less than 25 alcohol/ day)years, less than 40 pack-years and with AC/CC LIG1 genotype). CONCLUSION: The analysis suggested there was weak evidence of the association between LIG1 polymorphisms and head and neck cancers risk. Nonetheless, the results implied a strong modifying effect of both the alcohol and tobacco combined for the effect of LIG1 polymorphisms on the risk of head and neck cancers.
P07 ASSESSING ACTIVITIES ASSOCIATED WITH TIME SPENT OUTDOORS IN AN OCCUPATIONAL COHORT OF RADIOLOGIC TECHNOLOGISTS RK Kwok1, T Fears2, RA Kleinerman2, DM Freedman2, BH Alexander3, D Kampa3, RE Johnson1, MS Linet2, 1 RTI International, Research Triangle Park, NC, 2Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, 3Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN PURPOSE: To identify key daily activities in which persons working as radiologic technologists spend the majority of time outdoors. The findings will be used to design improved questionnaires to estimate retrospective UV exposure for future casecontrol studies of skin cancer and other malignancies to be undertaken within a large cohort of these medical radiation workers. METHODS: We evaluated the self-reported activities undertaken during time spent outdoors between 9 AM and 5 PM for 125 individuals (ages 40–59 and 60+ years old) who filled out a 7–day daily activity diary in September 2004. Daily UV measurements were also recorded for each individual. We initially classified activities into 37 groupings of similar activities before determining the 7 activities that accounted for the majority of time spent outdoors. We evaluated differences by age, gender, and geographic location of the individual in addition to whether these activities were carried out on a weekday or weekend day.
AEP Vol. 15, No. 8 September 2005: 630–665
RESULTS: Of a possible 13,953 daily diary entries, we ascertained that 4697 entries (totaling 1408 hours) were associated with time spent outdoors. The 7 major categories, which accounted for over 93% of the total time spent outdoors, included driving, yard work, home maintenance, walking or doing errands, recreational activities or sports, water activities, and leisure activities or relaxing outside. Differences in time spent outdoors were noted for age, gender, and weekend versus weekday. CONCLUSION: The results of this analysis, in conjunction with UV measurements, will be useful in developing questionnaires that more accurately estimate UV exposure in relation to cancer risks in future case-control studies.
P08 A META-ANALYSIS OF OCCUPATIONAL TRICHLOROETHYLENE EXPOSURE AND SELECTED CANCERS MA Kelsh1, M Weingart1, JH Mandel1, PJ Mink1, DD Alexander1, R Basu1, M Goodman2, 1Exponent, Inc., Menlo Park, CA, Oakland, CA; Chicago, IL; Washington, DC, 2Rollins School of Public Health, Emory University, Atlanta, GA PURPOSE: This review and meta-analysis evaluated occupational studies of TCE exposure and leukemia, non-Hodgkin’s lymphoma (NHL), and cancers of the lung, kidney, liver, and esophagus. METHODS: We summarized findings among occupational cohort studies and case-control studies that attempted to specifically identify and characterize TCE exposure. We identified 25 epidemiologic studies that met our inclusion criteria (17 cohort studies, 8 case-control studies). Cohort studies were categorized into ‘‘Group 1’’ and ‘‘Group 2’’ studies by type of exposure information available. RESULTS: The meta-analysis relative risk estimates (mRR) for kidney cancer suggested homogeneity of findings across studies in the Group 1 category (p value Z 0.97) with similar findings among U.S., European, and Aerospace/Aircraft studies. For liver cancer, mRR estimates varied. Aerospace/aircraft workers and Group 2 studies showed no association, whereas across European studies the mRR was slightly elevated. The findings for NHL indicated significant heterogeneity with lower mRRs among United States and aerospace/aircraft worker studies compared to a higher mRR for the European studies. Findings for esophageal cancer across studies were also heterogeneous. Similar to liver cancer and NHL, a pattern of higher mRRs was noted among European studies compared to other subgroups. CONCLUSION: This meta-analysis of occupational TCE exposure and NHL, leukemia, and cancers of the kidney, liver, esophagus, and lung showed no associations with lung and leukemia and inconsistent associations for kidney, liver, NHL and esophageal cancers across the Group 1 cohort studies considered as more informative. Heterogeneity of findings, limitations in exposure assessment and exposure comparability, and differences in disease classification limit interpretation of the epidemiologic data.