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Lung cancer rates in Israeli Jews have remained stable over the last five decades and are much lower than in most developed countries despite high historical smoking rates. We compared lung cancer risk in Jews and non-Jews in Israel and in the United States. Data were derived from a population-based, case-control study in Israel (638 cases, 496 controls) to estimate lung cancer risk associated with smoking. Data were also acquired from a case-control study in the United States with information on religious affiliation (5,093 cases, 4,735 controls). Smoking was associated with lung cancer risk in all religion/gender groups in both studies. However, major differences in risk magnitude were noted between Jews and non-Jews; ever smoking was associated with a moderately elevated risk of lung cancer in Jewish men and women in Israel (OR = 4.61, 2.90-7.31 and OR = 2.10, 1.36-3.24, respectively), and in Jewish men and women in the United States (OR = 7.63, 5.34-10.90 and OR = 8.50, 5.94-12.17) but were significantly higher in Israeli non-Jewish men (OR = 12.96, 4.83-34.76) and US non-Jewish men and women (OR = 11.33, 9.09-14.12 and OR = 12.78, 10.45-15.63). A significant interaction between smoking and religion was evident in light, moderate and heavy male and female smokers. The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions). Data from the two studies support the notion of a reduced risk of lung cancer in Jewish compared to non-Jewish smokers in different areas of the world.

Numerous prospective and retrospective studies have clearly demonstrated a dose-related increased lung cancer risk associated with cigarette smoking, with evidence also for a genetic component to risk. In this study, using the two-stage clonal expansion stochastic model framework, for the first time we investigated the roles of both genetic susceptibility and smoking history in the initiation, clonal expansion, and malignant transformation processes in lung carcinogenesis, integrating information collected by a case–control study and a large-scale prospective cohort study. Our results show that individuals with suboptimal DNA repair capacity have enhanced transition rates of key events in carcinogenesis.

Lung cancer accounts for 20% of cancer incidence in the United States and 25% of cancer-related deaths. Approximately 80% of lung cancer cases are non-small cell lung cancer (NSCLC). Deficiencies in DNA repair capacity (DRC), apoptosis control and cell cycle checkpoints have been implicated in the pathogenesis of lung cancer including NSCLC.1–3 Therefore, the essential role of the ATM protein in double strand break (DSB) DNA damage response and the importance of the DNA repair system in tobacco-related carcinogenesis highlight the potential significance of ATM sequence variations on NSCLC risk. ATM is a tumor suppressor gene frequently mutated in patients with Ataxia Telangiectasia (AT), a rare form of an autosomal recessive malignancy-prone disorder prominently characterized by extremely high sensitivity to ionizing radiation or other DSB-inducing agents.4 ATM encodes a 370-kDa phosphoinositide 3-kinase (PI3K) protein that belongs to the PI3K-like Serine/Threonine protein kinase (PIKK) family. This family functions in DNA damage responses by phosphorylating proteins in various damage-related pathways.5 ATM exists in an inactive multimer form in the cell nucleus, which dissociates into monomers upon exposure to DSB-inducing genetic insults.6 The interaction between the MRN (MRE11, RAD50, NBS1) complex and ATM in the presence of damaged DNA yields a more than 80-fold increase in ATM kinase activity, which is capable of relating the signals to a plethora of downstream effectors through phosphorylation of specific serine or threonine amino acid residues.7 The converging effects of these protein effectors control the outcome of the damaged cells through the regulation of cell cycle arrest, DNA repair and apoptosis. Aberrations of ATM protein have been implicated in the etiology of many cancers,8–13 including lung cancer. Through phosphorylating p53 and MDM2 proteins, ATM disrupts the p53-MDM2 interaction and thus, increases the nuclear accumulation of p53.5 Consistent with this notion, Bartkova et al. found that ATM, CHK2, p53 and H2AX were highly expressed and phosphorylated in early precursor lesions of various cancers, suggesting that the ATM-CHK2-p53 axis plays an essential role in the DNA damage-response in the early development stage of these malignancies, including lung cancer.14 Moreover, Eymin et al. reported that the ATM/CHK2 pathway also mediates the p14ARF-induced G2 cell cycle checkpoint arrest in response to DNA damaging agents. This pathway is independent of p53 activation and its defects contribute to lung carcinogenesis.14 Taken together, these observations highlight the pivotal role of ATM in the prevention of lung cancer development through the modulation of multiple pathways. However, most previous studies focused on the carcinogenic effect of ATM rare mutations rather than common variants. In a few studies in which ATM polymorphisms were investigated, controversial results have been reported in terms of the involvement of ATM polymorphisms in the etiology of malignancies such as breast and colorectal cancers.15–20 There have not been any studies of ATM polymorphisms and lung cancer risk in Caucasians. In addition, although ATM haplotypes have also been associated with altered cancer risk, most published studies focused on only breast cancer and the haplotypes in these studies were composed of only potential functional SNPs but were not based on haplotype tagging SNPs (htSNP).15,21–23 Since Bonnen et al. reported extensive linkage disequilibrium (LD) across the complete ATM locus which suggested that few htSNPs were required to construct complete high-power haplotypes to capture common ATM polymorphisms,24 a comprehensive approach combining the power of htSNPs and functional SNPs may provide more clues to the assessment of ATM sequence variants on cancer risk. To test the hypothesis that common ATM sequence variants may modulate NSCLC risk, we assessed the associations of 11 potential ATM htSNPs and functional SNPs with NSCLC risk in Caucasians. In addition, we performed a functional assay to evaluate the physiological significance of the observed associations through genotype–phenotype correlation analyses. To the best of our knowledge, this is the first epidemiological study examining the role of ATM polymorphisms in NSCLC risk in Caucasians.

The authors evaluated the familial aggregation of lung and other cancers in first-degree relatives of lung cancer patients self-reported to be lifetime never smokers. The data, derived from a large lung cancer case-control study, included 2,465 first-degree relatives of 316 never smoker lung cancer cases and 2,441 first-degree relatives of 318 never smoker controls, frequency matched to the cases on age, gender and ethnicity. The median age of the cases and the controls was 61 years, about 2/3 were women, and about 80% were Caucasian. Overall, there was a 25% excess risk [95% CI (1.05-1.50)] of any type of cancer among the first-degree relatives of cases, and case offspring exhibited a 2-fold excess cancer risk (1.03-4.10) compared with control offspring. There was also a 44% excess risk (1.05-1.97) of young onset cancers (before age 50) among relatives of cases. Smoking case relatives had an increased risk of any cancer [odds ratio (OR) = 1.36 (1.03-1.81)] and a 5.52-fold risk (1.19-25.51) of young onset lung cancer compared with smoking control relatives. Female case relatives had a 58% excess breast cancer risk (1.04-2.43), and case mothers a 2.57-fold breast cancer risk (1.16-4.24). A significant excess of testicular cancer was observed among case male relatives [OR = 12.32 (1.71-88.90)], although based on only 9 cases. The age at lung cancer diagnosis tended to be earlier in case relatives (61.4, SD = 12.9) compared with control relatives (66.2, SD = 11.4; p = 0.07). Our analysis provides further evidence for the importance of genetic factors for lung cancer in never smokers.

Zinc, copper and selenium are important cofactors for several enzymes that play a role in maintaining DNA integrity. However, limited epidemiologic research on these dietary trace metals and lung cancer risk is available. In an ongoing study of 1,676 incident lung cancer cases and 1,676 matched healthy controls, we studied the associations between dietary zinc, copper and selenium and lung cancer risk. Using multiple logistic regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for all subjects by increasing quartiles of dietary zinc intake were 1.0, 0.80 (0.65-0.99), 0.64 (0.51-0.81), 0.57 (0.42-0.75), respectively (p trend = 0.0004); similar results were found for men. For dietary copper, the ORs and 95% CI for all subjects were 1.0, 0.59 (0.49-0.73), 0.51 (0.41-0.64), 0.34 (0.26-0.45), respectively (p trend0.0001); similar reductions in risk and trend were observed by gender. Dietary selenium intake was not associated with risk, except for a significant inverse trend (p = 0.04) in men. Protective trends (p0.05) against lung cancer with increased dietary zinc intake were also found for all ages, BMI25, current smokers, pack-yearsor =30, light drinkers and participants without emphysema. Increased dietary copper intake was associated with protective trends (p0.05) across all ages, BMI, smoking and vitamin/mineral supplement categories, pack-yearsor =30 and 30.1-51.75 and participants without emphysema. Our results suggest that dietary zinc and copper intakes are associated with reduced risk of lung cancer. Given the known limitations of case-control studies, these findings must be interpreted with caution and warrant further investigation.

Individuals differ in their ability to repair DNA damage induced by carcinogens. Studies have shown that polymorphisms in DNA repair genes contribute to individual variation in DNA repair capacity and cancer risk. In a hospital-based case-control study, we tested the hypothesis that a C to T variant (Thr241Met) of DNA repair gene X-ray repair cross-complementing group 3 (XRCC3) is associated with risk of developing squamous cell carcinoma of the head and neck (SCCHN). We genotyped for this variant in 367 non-Hispanic white patients newly diagnosed with SCCHN and 354 frequency-matched cancer-free controls. Compared with the XRCC3 18067CC and 18607CT genotypes, the variant XRCC3 18067TT genotype was associated with a non-statistically significantly increased risk of SCCHN (adjusted odds ratio [ORadj], 1.36; 95% confidence interval [CI], 0.89-2.08), but this risk was significantly increased among female subjects (ORadj 2.23, 95% CI, 1.00-4.98) and current smokers (ORadj, 2.26; 95% CI, 1.02-4.99). These findings suggest that the variant XRCC3 18067TT genotype may not play a major role in the etiology of SCCHN but may contribute to a subset of SCCHN. Larger studies are needed to verify these findings.

Lung cancer rates in Israeli Jews have remained stable over the last five decades and are much lower than in most developed countries despite high historical smoking rates. We compared lung cancer risk in Jews and non-Jews in Israel and in the United States. Data were derived from a population-based, case-control study in Israel (638 cases, 496 controls) to estimate lung cancer risk associated with smoking. Data were also acquired from a case-control study in the United States with information on religious affiliation (5,093 cases, 4,735 controls). Smoking was associated with lung cancer risk in all religion/gender groups in both studies. However, major differences in risk magnitude were noted between Jews and non-Jews; ever smoking was associated with a moderately elevated risk of lung cancer in Jewish men and women in Israel (OR = 4.61, 2.90-7.31 and OR = 2.10, 1.36-3.24, respectively), and in Jewish men and women in the United States (OR = 7.63, 5.34-10.90 and OR = 8.50, 5.94-12.17) but were significantly higher in Israeli non-Jewish men (OR = 12.96, 4.83-34.76) and US non-Jewish men and women (OR = 11.33, 9.09-14.12 and OR = 12.78, 10.45-15.63). A significant interaction between smoking and religion was evident in light, moderate and heavy male and female smokers. The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions). Data from the two studies support the notion of a reduced risk of lung cancer in Jewish compared to non-Jewish smokers in different areas of the world.

Low dietary folate intake has been associated with increased risk of gastric cancer. The 5,10-methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has 2 variants, C677T and A1298C, that result in decreased MTHFR activity and lower plasma folate levels. Therefore, we hypothesized that these 2 variants play a role in gastric carcinogenesis. We tested this hypothesis in a Chinese population-based case-control study of 187 histopathologically confirmed gastric cancer cases and 166 healthy controls frequency-matched by age (+/-5 years), gender and residential area. The 677TT genotype was associated with increased risk for gastric cancer [adjusted odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.00-3.48] compared to the 677CC genotype. This association was more pronounced for gastric cardia cancer (adjusted OR = 2.47, 95% CI = 1.14-5.32). However, no evidence was found for risk associated with the MTHFR A1298C polymorphism. Our findings support the hypothesis that MTHFR C677T variants contribute to gastric carcinogenesis, particularly in gastric cardia. Larger studies incorporating dietary folate intake and serum levels are needed to confirm our findings.

The level of DNA adducts under the same conditions of carcinogen exposure and cell proliferation reflects an integrated measure of carcinogen metabolism and DNA repair. Therefore, such DNA adduct levels have the potential to be a biomarker for susceptibility to chemical carcinogenesis. In a pilot study of 91 patients with squamous cell carcinomas of the head and neck and 115 controls who were frequency matched by age, sex, ethnicity, and smoking status, we applied a newly developed in vitro assay of benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in short-term peripheral lymphocytes cultures. Levels of BPDE-DNA adducts were found to be significantly higher in cases than in controls (mean ± SD, 76.8 ± 77.4/107 and 47.1 ± 48.0/107 nucleotides, respectively; p < 0.001). Using the median level of control values (35/107) as the cut-off point, about 66% of cases were distributed above this level. Logistic regression analysis revealed that the level of BPDE-induced DNA adducts was an independent risk factor (odds ratio = 2.22; 95% confidence interval = 1.22–4.04) after adjustment for age, sex and smoking status. Further stratified analyses showed that levels of the induced adducts between cases and controls were significantly higher in both age groups, that is, younger or older than 60, as well as in both men and women. Smoking had a positive effect on the induced adducts. The highest level of induced adducts was seen in current smokers, then former smokers and non-smokers. There was a statistically significant dose–response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of head and neck cancer (trend test, p = 0.003). Despite the relatively small sample size, the association of BPDE-induced DNA adducts and cancer risk suggests that this assay has the potential to complement with other biomarkers in identifying individuals at increased risk of developing tobacco-related cancers. © 2001 Wiley-Liss, Inc.

While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a universitybased hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were

Gastric cancer remains the leading cause of cancer death in China and other countries in eastern Asia. Studies of gastric cancer have revealed that it is a disease of complex etiology involving dietary, infectious, environmental, occupational and genetic factors. DNA repair capacity has been suggested as a genetic factor contributing to variation in susceptibility to cancer. In the present study, we described an association between 2 polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. We used a polymerase chain reaction-based assay to detect Pvu II and Nci I restriction fragment length polymorphisms (XRCC1 26304 CT and XRCC1 28152 GA, respectively) in 188 patients with gastric cancer and 166 healthy controls. The XRCC1 26304 T allele (194Trp) frequency (34.6%) was higher and the XRCC1 28152 A allele (399Gln) frequency (25.6%) was lower in healthy Chinese controls than previously reported healthy U.S. Caucasian controls (7.2% and 34.1%, respectively). Multivariate logistic regression analysis revealed that the putative high-risk genotypes XRCC1 26304 CC and XRCC1 28152 GA/AA were associated with a non-significant increased risk for gastric cancer (adjusted odds ratio [OR]=1.45, 95% confidence interval [CI]= 0.93–2.25 and OR=1.53, 95% CI= 0.98–2.39, respectively) compared with other genotypes. However, the XRCC1 26304 CC genotype was associated with a significantly increased risk for gastric cardia cancer (adjusted OR=1.86, 95% CI=1.09–3.20). Individuals with both putative high-risk genotypes (CC and GA/AA) had a significantly higher risk (ad-justed OR=1.73, 95% CI=1.12–2.69), particularly for gastric cardia cancer (adjusted OR=2.18, 95% CI=1.21–3.94) than individuals with other genotypes. These findings support the hypothesis that these 2 XRCC1 variants may contribute to the risk of developing gastric cancer, particularly gastric cardia cancer. Int. J. Cancer 88:601–606, 2000. © 2000 Wiley-Liss, Inc.

Differences in genetic susceptibility to tobacco-induced carcinogenesis appear to modulate an individual's risk of squamous-cell carcinoma of the head and neck (SCCHN). Risk for SCCHN may be associated with the null alleles of the carcinogen-metabolizing genes glutathione-S-transferase (GST) T1 and GSTM1. In this study, we evaluated the association between GSTM1 and GSTT1 null genotypes and risk of SCCHN in a matched case-control study of 162 patients with SCCHN and 315 healthy controls. Our results showed that 53.1% of cases and 42.9% of controls were null for GSTM1, whereas 32.7% of cases and 17.5% of controls were null for GSTT1 (p < 0.05 and p < 0.001, respectively). Furthermore, 19.8% of cases but only 7.9% of controls were null for both genes (p < 0.001). Multivariate analysis using logistic regression models, including age, sex, ethnicity, smoking status, alcohol status and GST genotypes, showed that both of these genotypes remained independent risk factors for disease [adjusted odds ratios (ORs) = 1.50 and 2.27, respectively; 95% confidence intervals (CIs) = 1.01–2.23 and 1.43–3.60, respectively). When the genotypes were divided into neither null, either null or both null, there was a dose-response relationship (adjusted OR = 1.50, 95% CI = 0.98–2.30) for the either-null group and (adjusted OR = 3.64, 95% CI = 1.94–6.84) for the both-null group (p < 0.001, trend test). Our findings suggest that the GSTM1 and GSTT1 null genotypes are independent risk factors for SCCHN and markers for genetic susceptibility to tobacco-induced carcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:220–224, 1999. © 1999 Wiley-Liss, Inc.

The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case-control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1–3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3–25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2–429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2–57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.

Studies of vitamin E and cancer have focused on the alpha-tocopherol form of the vitamin. However, other forms of vitamin E, in particular gamma-tocopherol may have unique mechanistic characteristics relevant to lung cancer prevention. In an ongoing study of 1,088 incident lung cancer cases and 1,414 healthy matched controls, we studied the associations between 4 tocopherols (alpha-, beta-, gamma-, and delta-tocopherol) in the diet and lung cancer risk. Using multiple logistic regression analysis, the adjusted odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for increasing quartiles of dietary alpha-tocopherol intake were 1.0, 0.63 (0.50-0.79), 0.58 (0.44-0.76) and 0.39 (0.28-0.53), respectively (p-trend0.0001). For dietary intake of beta-tocopherol, the OR and 95% CI for all subjects were: 1.0, 0.79 (0.63-0.98), 0.59 (0.45-0.78) and 0.56 (0.42-0.74), respectively (p-trend0.0001). Similar results for dietary gamma-tocopherol intake were observed: 1.0, 0.84 (0.67-1.06), 0.76 (0.59-0.97) and 0.56 (0.42-0.75), respectively (p- trend = 0.0002). No significant association between delta-tocopherol intake and lung cancer risk was detected. When the 4 tocopherols were summed as total tocopherol intake, a monotonic risk reduction was also observed. When we entered the other tocopherols in our model, only the association with dietary alpha-tocopherol intake remained significant; i.e., increasing intake of dietary alpha-tocopherol accounted for 34-53% reductions in lung cancer risk. To the best of our knowledge, this is the first report of the independent associations of the 4 forms of dietary tocopherol (alpha-, beta-, gamma- and delta-tocohperol) on lung cancer risk. Given the limitations with case-control studies, these findings need to be confirmed in further investigations.

Few studies have assessed mutagen sensitivity and lung cancer (LC) risk associations in the context of multiple epidemiological risk factors. We evaluated mutagen sensitivity as a susceptibility marker and explored the interplay of the genetic marker and multiple epidemiologic risk factors in modulating LC risk. This largest case–control study included 977 newly diagnosed LC patients and 977 controls, matched by age, gender, ethnicity and smoking status. Cases exhibited significantly higher mutagen sensitivity than controls in bleomycin (0.76 vs. 0.62 breaks/cell, p < 0.001) and benzo[a]pyrene diol epoxide (BDPE) assays (0.70 vs. 0.61 breaks/cell, p < 0.001). Mutagen sensitivity also exhibited dose-response relationship with LC risk in quartile analysis (p for trend

We performed an analysis of potential epidemiological risk factors for lung cancer using data from 280 cases and 242 hospital-based controls, all lifetime never smokers (those who had smoked

Folate deficiency is implicated in cancer risk that may be modulated by a genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene in folate metabolism. We hypothesized that genetic variants in MTHFR are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We genotyped 3 MTHFR polymorphisms (C677T, A1298C and G1793A) and estimated their haplotypes in a hospital-based case-control study of 537 SCCHN cases and 545 cancer-free controls. The controls were frequency-matched to the cases by age (+/- 5 years), sex, ethnicity and smoking status. We found that the MTHFR 1298AC/CC genotypes were associated with an approximately 35% reduction in risk of SCCHN (adjusted odds ratio = 0.65; 95% CI = 0.51-0.82) compared to the AA genotype. The MTHFR 677CT and 1793GA/AA genotypes were associated with nonsignificant increased risk of SCCHN compared to the 677CC and 1793GG genotypes, respectively. We estimated that there were 8 haplotypes and 16 haplotype genotypes based on these 3 variants. When we used the haplotypes and assumed that the 677T, 1298A and 1793A alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.85 (1.3-2.5) for any 2 risk alleles and 1.93 (1.4-2.7) for any 3 risk alleles. These results suggest that all 3 MTHFR polymorphisms may play a role in the susceptibility to SCCHN among non-Hispanic whites. Future studies should incorporate detailed data on alcohol consumption, dietary folate intake and related serologic measurements.

Tobacco-related carcinogens cause a variety of DNA damage that is repaired by different enzymatic pathways, suggesting that DNA repair plays an important role in tobacco-induced carcinogenesis. In a large hospital-based case-control study, we investigated DNA repair capacity (DRC) as a biomarker for susceptibility to nonsmall cell lung cancer (NSCLC) and evaluated the possible interaction between DRC and tobacco smoke in 467 newly diagnosed NSCLC patients and 488 cancer-free controls. We measured DRC in cultured peripheral lymphocytes using the host-cell reactivation assay with a reporter gene damaged by an activated tobacco carcinogen, benzo[a]pyrene diol epoxide. The results showed that current smokers exhibited the highest DRCs as compared to former and nonsmokers both among patients and control subjects. There were no differences of DRC among 3 different histopathologic types of NSCLC. Logistic regression analysis revealed that suboptimal DRC and pack-years smoked were independent predictors of NSCLC risk. The overall 15.5% reduction in DRC observed in the cases (7.84%) compared to the controls (9.28%) (p

Cytogenetic aberrations on chromosome 9 have been reported to be one of the most frequent genetic changes in lung tumorigenesis. Although many of these changes have been detected in lung carcinoma specimens, there is growing evidence showing the concordance between chromosomal alterations in primary lung tumors and peripheral blood lymphocytes (PBLs). We investigated whether spontaneous aberrations on chromosome 9 in PBLs are associated with the presence of lung cancer and with a family history of cancer. A personal interview, to construct a detailed epidemiologic profile including family history of cancer, was conducted on 174 lung cancer cases and 162 matched controls. One hundred metaphases from PBLs of each subject were analyzed for chromosome 9 aberrations using the whole chromosome painting technique. Overall, the mean proportion of individuals with chromosome 9 abnormalities in their PBLs was significantly higher in cases (96.0%) than in controls (60.5%) (p < 0.05). After adjustment by age, gender, ethnicity, family size, and pack-years, there was a 16.63-fold significantly elevated odds ratio (OR) for lung cancer associated with chromosome 9 aberrations. When subjects were categorized by frequencies of the chromosome 9 lesions, we observed significantly increased odds ratios of 11.13 (4.66, 26.58) and 27.45 (11.15, 67.54) for individuals with 1 chromosome 9 aberration and ≥2 chromosome 9 aberrations, respectively. By performing family history analyses, we further observed that control individuals with chromosome 9 aberrations were more likely to report a family history of any cancer (OR = 1.67 [0.84, 3.32]) and lung cancer (OR = 2.49 [0.81, 7.67]). Our findings suggest that chromosome 9 aberrations in PBLs might be considered a marker of lung cancer predisposition and may be associated with familial aggregation of cancer. © 2002 Wiley-Liss, Inc.

Descriptive epidemiological findings for 7,696 patients with newly diagnosed thyroid cancer reported to the Surveillance, Epidemiology, and End Results (SEER) program for the years 1973 through 1981 are summarized. The preponderance of this tumor in women and of the papillary histologic subtype are well documented. The data suggest that previously reported increases in the incidence of thyroid cancer among Whites levelled off in the late 1970s. Differences in the incidence of this cancer according to ethnic group were particularly striking. Compared with White men and women, Puerto Rico Hispanics and Blacks had significantly lower thyroid cancer rates (weighted rate ratios ranged from 0.48 to 0.65). New Mexico Hispanic men and Chinese, Japanese, Hawaiian and Filipino men and women had significantly higher rates (weighted rate ratios ranged from 1.56 to 3.17). Elevated thyroid cancer rates for residents of Hawaii, regardless of ethnic group, were also a noteworthy finding. Variations in thyroid cancer risk according to ethnic group and geographical residence may reflect socio-economic or local environmental influences, including the possibility of a carcinogenic agent in volcanic lava.