A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking

Gang Liang, Xiaoping Miao, Yifeng Zhou, Wen Tan and Dongxin Lin1

Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

1 To whom correspondence should be addressed Email: dlin{at}public.bta.net.cn


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Sulfotransferase 1A1, an important member of sulfotransferase superfamily, is involved in the biotransformation of many compounds including tobacco carcinogens. A single nucleotide polymorphism (G638A) in the sulfotransferase 1A1 (SULT1A1) gene causes Arg213His amino acid change and consequently results in significantly reduced enzyme activity and thermostability. We thus hypothesized that the variant SULT1A1 allele may protect against the risk of lung cancer related to tobacco smoking. To examine this hypothesis, we analyzed 805 patients with lung cancer and 809 controls for this polymorphism in a hospital-based, case-control study. We observed that, compared with the GG genotype, the variant SULT1A1 genotype (638GA or AA) was associated with a significantly increased risk for overall lung cancer [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.44–2.37]. Stratification analysis showed that the increased risk of lung cancer related to the variant SULT1A1 genotypes was more pronounced in younger subjects and limited to smokers but not non-smokers [OR 2.28 (95% CI 1.66–3.13) versus OR 1.35 (95% CI 0.91–1.99); P for homogeneity = 0.000]. Furthermore, the risk of lung cancer for the variant genotypes was increased consistently with cumulative smoking dose, with the ORs being 1.66 (95% CI, 0.75–3.68), 2.28 (95% CI, 1.47–3.54) and 3.35 (95% CI, 1.71–6.57) for those who smoked <15 pack-years, 15–36 pack-years and >36 pack-years, respectively (P for trend = 0.000). When analysis was stratified by histological subtypes of lung cancer, consistent results were observed for all three major types of the cancer, i.e. squamous cell carcinoma, adenocarcinoma and other types. Our results, which are against the original hypothesis, demonstrate that the variant SULT1A1 638A allele is associated with susceptibility to lung cancer in relation to tobacco smoking.

Abbreviations: CI, confidence interval; OR, odds ratio; PAHs, polycyclic aromatic hydrocarbons; SCC, squamous cell carcinoma; SULT1A1, sulfotransferase 1A1


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
During the last two decades, the rates of incidence and mortality of lung cancer in China have been increasing significantly and constantly (1). Tobacco smoking and indoor air pollution derived from Chinese-style cooking and/or coal burning has been shown to be the major cause of lung cancer in China (26). However, although risk of lung cancer has been conclusively associated with tobacco smoking and perhaps indoor air pollution, only a portion of exposed individuals develop the cancer in their life span, indicating that there may be important genetic basis rendering such individuals more susceptible to the disease. Most tobacco smoke- and air pollutant-derived carcinogens require metabolic activation to form DNA damage and induce genotoxicity (7,8). Thus, it is rational to postulate that carcinogen-metabolizing enzymes may play a role in lung carcinogenesis and their activities may mediate susceptibility to lung cancer among exposed individuals. In recent years, a great number of studies have shown, although not all results are in agreement, that genetic polymorphisms in certain carcinogen-metabolizing enzymes, such as cytochrome P450 s, N-acetyltransferases and glutathione S-transferases, are risk modifiers of lung cancer in relation to tobacco smoking and/or environmental pollution (913). Identification of such genetic factors may be helpful in better understanding gene–environment interaction in the risk of lung cancer and developing more effective strategies for the cancer detection and prevention.

Sulfotransferases (SULTs), a superfamily of multifunctional enzymes, catalyze sulfonate conjugation that is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfonation is generally considered as a detoxification mechanism, which generates more water-soluble and often less toxic metabolites; however, this conjugation reaction of certain compounds may produce electrophiles that can bind to DNA to form carcinogen–DNA adducts (reviewed in refs 1417). Sulfotransferase 1A1 (SULT1A1), an important member of this enzyme superfamily, has high activity towards a wide range of substrates including environmental and tobacco carcinogens. For instance, SULT1A1 may catalyze the sulfonation of N-hydroxy derivatives of arylamines and heterocyclic amines, both are presented in tobacco smoke, to form more reactive DNA-damaging electrophiles (18,19). Sulfonation may also activate another major class of tobacco carcinogens, polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (2022), although the relative importance of this SULT1A1-requiring pathway in human tissues is unclear. The SULT1A1 protein is widely expressed in various tissues including the lung (23,24); however, its activity has been shown to exhibit a marked variation among individuals (14,2527). The importance of SULT1A1 in biotransformation of carcinogens suggests that this polymorphic enzyme activity may have the potential to influence susceptibility to chemical carcinogenesis in humans.

Several single nucleotide polymorphisms have been found in the SULT1A1 gene (2729), one of them located in the coding region (638G to A) leads to an Arg213His amino acid change (27) and occurs in relatively high but various frequencies in different ethnic populations (2931). Functional studies have revealed that the variant A allele (SULT1A1*2) is associated with remarkably reduced sulfotransferase activity in platelets compared with the wild-type G allele (SULT1A1*1) (27,32,33). In view of the role played by SULT1A1 in the metabolism of carcinogens and strong reduction of SULT1A1 activity resulted from the G638A polymorphism, several molecular epidemiological studies have examined the relationship between the polymorphism and risk of certain cancers (3443). However, the results from these previous studies are conflicting and some findings appear to be contrary to the prior hypothesis, thus warranting additional studies to address the role of the gene in human carcinogenesis. So far, only one study on lung cancer in Caucasians has been published, showing a positive association between this polymorphism in SULT1A1 and increased risk of the cancer (42).

We have therefore carried out a more comprehensive case-control study among Chinese to further examine the hypothesis that the SULT1A1 polymorphism, which encodes low activity allozyme, may protect against risk of lung cancer. In this study, we emphatically evaluated the interaction between the SULT1A1 genotype and tobacco smoking.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Study subjects
All study subjects were ethnically homogenous Han Chinese and participants in a previously reported molecular epidemiological study consisting of 1006 lung cancer cases and 1020 controls (44). In this study, we genotyped 810 cases and 810 controls because some DNA samples used in the previous study are no longer available. The cases were patients with primary lung cancer recruited from January 1997 to June 2002 at the Cancer Hospital, Chinese Academy of Medical Sciences (Beijing). They were newly diagnosed, histologically confirmed and previously untreated (by radiotherapy or chemotherapy) incident cases. The histological types of the cancer were determined by postoperative histopathological examination or biopsy via bronchoscopy. All histological classifications were determined by senior pathologists of the hospital. Patients were from Beijing City and its surrounding regions and there were no age, sex and histology restrictions. The exclusion criteria included previous cancer, metastasized cancer from other organs, previous radiotherapy or chemotherapy. Population controls were randomly selected from a pool of 2800 cancer-free individuals recruited from a nutritional survey conducted in the same region during the same time period as the cases were collected (44). The selection criteria included no individual history of cancer based on a physical examination and frequency-matched to lung cancer cases on age (±5 years) and sex. At recruitment, informed consent was obtained from each subject and each participant was then interviewed to collect detailed information on demographic characteristics and lifetime history of tobacco use. The participation response rate of this study was 91% among patients and 87% among controls. The study was approved by the Institutional Review Board of the Chinese Academy of Medical Sciences Cancer Institute.

SULT1A1 genotyping
Genomic DNA from control and case subjects was extracted from peripheral blood. The SULT1A1 genotypes at the G638A site were analyzed by polymerase chain reaction (PCR)-based restriction fragment length polymorphism methods. The primers used for amplification of the target fragment were SULTF5'-GGG TCT CTA GGA GAG GTG GC-3' and SULTR5'-GCT GTG GTC CAT GAA CTC CT-3', which produce a 270-bp exon 7 region of the SULT1A1 gene containing the G638A site (36). PCR was performed with a 25-µl reaction mixture containing ~100 ng DNA, 1.0 µM each primer, 0.2 mM each dNTP, 2.0 mM MgCl2, 1.0 U Taq DNA polymerase with 1x reaction buffer (Promega, Madison, WI) and 2% dimethylsulfoxide. The reaction was carried out in the following conditions: an initial melting step of 2 min at 95°C, followed by 35 cycles of 30 s at 94°C, 30 s at 58°C and 45 s at 72°C and a final elongation of 7 min at 72°C. The PCR products were then digested with restriction enzyme HhaI (New England Biolabs, Beverly, MA) and separated on a 2.5% agarose gel. The wild-type G allele had a HhaI restriction site that resulted in two bands (155 and 115 bp), and the A allele lacked the HhaI restriction site and thus produced a single 270-bp fragment. The genotypes identified by HhaI digestion were confirmed by DNA sequencing. Genotyping was performed without knowledge of subjects' case or control status and a 15% masked, random sample of cases and controls was tested twice by different persons and the results were concordant for all masked duplicate sets. The SULT1A1 genotypes were successfully determined for all but five cases and one control, yielding 805 cases and 809 controls for data analysis.

Statistical analysis
{chi}2 tests were used to examine the differences in the distributions of genotypes between cases and controls. The association between the SULT1A1 polymorphism and risk of lung cancer was estimated by odds ratio (ORs) and their 95% confidence interval (CIs), which were calculated by unconditional logistic regression. Smokers were considered current smokers if they smoked up to 1 year before the date of cancer diagnosis or the date of the interview for control subjects. Information was collected on the number of cigarettes smoked per day, the age at which the subjects started smoking and the age at which ex-smokers stopped smoking. Pack-year smoked was calculated to indicate cumulative cigarette dose [pack-years = (cigarettes per day/20) x (years smoked)]. Light, moderate and heavy smokers were categorized by the 25th, 50th and 75th percentile pack-year value of the controls, i.e. <15 pack-years, 15–36 pack-years and >36 pack-years. Because only 26 patients and 38 controls were ex-smokers, they were combined with current smokers for analysis. The ORs were all adjusted for age, sex and smoking status or pack-years where it was appropriate. The probability level of <0.05 was used as the criterion of significance. We tested the null hypotheses of additivity and multiplicativity and evaluated the departures from additive and multiplicative interaction models (45). A more than additive interaction was indicated when OR11 > OR10 + OR01 – 1, where OR11 = OR when both factors are present, OR10 = OR when only factor 1 is present, and OR01 = OR when only factor 2 is present. A more than multiplicative interaction was suggested when OR11 > OR10 x OR01. Departures from these additive and multiplicative models were assessed by including main effect variables and their product terms in the logistic regression model. All analyses were performed using Statistical Analysis System (Version 6.12, SAS Institute, Cary, NC).


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The distributions of age, sex, smoking status and histological types of lung cancer in the study subjects are summarized in Table I. The case patients and control subjects appeared to be adequately matched on sex and age. The mean age was 58.0 years (±10.5 years; range, 27–78 years) for the case patients and 58.1 years (±7.7 years; range, 30–81 years) for the control subjects (P = 0.730). There was no significant difference between the case patients and control subjects in terms of sex distribution (73.8% males in cases versus 74.5% males in controls, P = 0.732). However, more smokers were presented in the case group compared with the controls (66.6 versus 53.8%; P = 0.000). In addition, cases had a higher value of pack-years smoked than controls; 39.4% smokers among cases smoked >36 pack-years while this value was 24.4% among controls (P = 0.000). Among the lung cancer patients, 396 (49.2%) were classified as squamous cell carcinoma (SCC), 240 (29.8%) as adenocarcinomas and 169 (21.0%) as other types including undifferentiated cancers (n = 66), bronchioalveolar carcinomas (n = 62) and mixed cell carcinomas (n = 41).


View this table:
[in this window]
[in a new window]
 
Table I. Frequency distribution of select characteristics by case-control status

 
Table II shows allele frequencies and genotype distributions of SULT1A1 by case and control status. In case patients, the frequencies of the common G allele and minor A allele were respective 85.7 and 14.3%, which differed significantly from those (91.3 and 8.7%) in control subjects (P = 0.000). We observed genotype frequencies of 72.2 (GG), 27.0 (GA) and 0.8% (AA) in case patients compared with respective 83.1, 16.6 and 0.3% in control subjects (P = 0.000), both of which fitted the Hardy–Weinberg equilibrium (P = 0.102 and 0.605, respectively). As the AA homozygotes were extremely rare in control subjects (0.3%) and case patients (0.8%), this genotype was combined with the GA genotype for the estimation of lung cancer risk. Logistic regression analysis showed that subjects carrying the GA or AA genotype had a ~2-fold increased risk of overall lung cancer (adjusted OR, 1.85; 95% CI, 1.44–2.37) compared with subjects carrying the GG genotype, indicating that the A allele is the risk allele.


View this table:
[in this window]
[in a new window]
 
Table II. Allele and genotype frequencies for SULT1A1 in cases and controls and their association with risk of overall lung cancer

 
Risk of lung cancer related to the SULT1A1 genotype was further examined with the stratifications by histological types of the cancer, sex, age, smoking status and pack-years smoked (Table III). It was found that increased risk of lung cancer associated with the variant GA or AA genotype remained significant after being stratified by histological subtypes, with the OR of 1.91 (95% CI, 1.40–2.62) for SCC, 1.70 (95% CI, 1.20–2.42) for adenocarcinoma, and 2.33 (95% CI, 1.59–3.42) for other types of lung cancer, respectively. The increased risk appeared to be more pronounced in subjects who were younger (<50 years) at diagnosis (adjusted OR, 2.15; 95% CI, 1.41–3.26) than in subjects who were >=50 years (adjusted OR, 1.72; 95% CI, 1.26–2.35), and in females (adjusted OR, 2.14; 95% CI, 1.32–3.50) than in males (adjusted OR, 1.75; 95% CI, 1.31–2.34). Furthermore, risk for the cancer related to this genetic variation in SULT1A1 favored smokers but not non-smokers [OR 2.28 (95% CI 1.66–3.13) versus OR 1.35 (95% CI 0.91–1.99); P = 0.000, test for homogeneity]. When smoking was additionally stratified by pack-years smoked, risk of lung cancer for the variant genotype (GA or AA) was increased consistently with cumulative smoking dose, with the ORs being 1.66 (95% CI, 0.75–3.68), 2.28 (95% CI, 1.47–3.54) or 3.35 (95% CI, 1.71–6.57) for those who smoked <15 pack-years, 15–36 pack-years or >36 pack-years, respectively (P = 0.000; test for trend), compared with the GG genotype within the respective strata (Table III), indicating an additive interaction between the genetic polymorphism and smoking in risk for development of lung cancer according to the statistical model (45).


View this table:
[in this window]
[in a new window]
 
Table III. Risk of lung cancer related to SULT1A1 genotypes by histological type, sex, age, smoking status and pack-years smoked

 
We also examined the effect of the SULT1A1 polymorphism on risk of subtypes of lung cancer by smoking status and pack-years smoked (Table IV). It was found that the GA or AA genotype had little or no effect on risk of the three major types of lung cancer among non-smokers. Among smokers, however, a substantial risk effect of the variant GA or AA genotype compared with the GG genotype was observed on SCC (adjusted OR, 2.21; 95% CI, 1.55–3.15), adenocarcinoma (adjusted OR, 1.81; 95% CI, 1.08–3.04) and other types of lung cancer (adjusted OR, 3.00; 95% CI, 1.87–4.83). When smoking was further stratified by pack-years, an additive interaction between the polymorphism and incremental smoking dose was evident in all three subgroups of lung cancer although the effect on adenocarcinoma was statistically significant only among subjects who smoked >36 pack-years.


View this table:
[in this window]
[in a new window]
 
Table IV. Risk of different subtypes of lung cancer related to SULT1A1 genotypes by smoking status and pack-years smoked

 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Because human SULT1A1 is an important enzyme in the metabolism of endogenous and exogenous carcinogens and the G638A polymorphism in SULT1A1 results in reduced enzyme activity and thermostability, we investigated whether the SULT1A1 genotype has an effect on the individual susceptibility to lung cancer development. We analyzed 805 lung cancer patients and 809 controls in a Chinese Han population and demonstrated that the variant SULT1A1 allele (GA or AA genotype) was associated with an increased risk of lung cancer. The increased risk associated with this genetic polymorphism remained significant when adjusted for age, sex and smoking, indicating that it is an independent risk factor. When the analysis was stratified by smoking exposure, the risk effect of the variant genotypes occurred only among smokers but not non-smokers and the risk for all subtypes of the cancer was increased in a manner of smoking dose-dependence, suggesting an additive interaction between the genetic polymorphism and smoking exposure. In addition, we found that the association between the SULT1A1 638GA or AA genotype and lung cancer risk appeared to be more pronounced in younger subjects (<50 years old). This finding is in line with the conception that genetic susceptibility is often associated with an early age of disease onset (46,47).

A few case-control studies have been published with regard to the association between the SULT1A1 polymorphism and risk of certain cancers, and thus provide comparison with our findings. One study (42) on lung cancer in Caucasians (463 cases and 485 controls) reported that the variant A allele of SULT1A1 was associated with an increased risk of the cancer (OR, 1.41; 95% CI, 1.04–1.91). Furthermore, these authors showed that risk related to the allele was significantly higher in females than in males and higher in current smokers and heavy smokers than in non-smokers. These previous results obtained from a Caucasian population are similar to our results in the present study conducted in a Chinese population. The consistent results of lung cancer studies in Caucasian and Chinese populations tend to support the notion that the SULT1A1 pathway may play a role in lung cancer development and its functional polymorphism may constitute a genetic basis for susceptibility to the cancer. Similar findings have also been reported in the studies on some other cancer sites. Wu et al. (40) genotyped 187 patients with esophageal cancer and 308 controls in a Chinese population in Taiwan and revealed a 3.53-fold increased risk (95% CI, 2.12–5.87) of the cancer for the SULT1A1 638GA genotype (no AA homozygote was identified in their study) compared with the GG genotype. Bamber et al. (37) also showed in their colorectal cancer study among Caucasians that a significantly reduced risk of the cancer (OR, 0.47; 95% CI, 0.27–0.83) was associated with the SULT1A1 638GG homozygotes in subjects under the age of 80 years. Recently, Tang et al. (41) reported that an increased risk of breast cancer was associated with the A allele and PAH–DNA adduct levels in breast tissue were not associated with SULT1A1 genotypes. In a case-only study on breast cancer, Saintot et al. (43) also showed that the smokers carrying the SULT1A1 A allele had a 2-fold excess risk for the cancer compared with never smokers carrying the GG genotype, suggesting that a lower sulfonation of the tobacco carcinogens among women with SULT1A1-His could increase exposure to genotoxic compounds. Taken together, these findings do not support the hypothesis based on in vitro model studies but suggest that the high activity SULT1A1-213Arg allozyme (the GG genotype) may protect against chemical carcinogens related to certain human cancers, such as PAHs, which are believed to be linked to lung cancer and breast cancer (48,49).

However, inconsistent results also exist to show null association between SULT1A1 genotype and risk of colorectal cancer (38) and prostate cancer (34) in Caucasian populations, and urothelial epithelial cancers in a Japanese population (39). On the other hand, Seth et al. (35) showed that the G allele was associated with a younger age of onset of breast cancer whereas it had no effect on overall risk of the cancer. Zheng et al. (36) reported that an overall risk of breast cancer was increased with the number of the SULT1A1 A allele, but the direction of the risk was reversed to the G allele among subjects exposed to well-done red meat, which is believed to contain high levels of heterocyclic amine carcinogens. Although the observations by these investigators in the breast cancer studies are somewhat conflicting and appear to be difficult to interpret with regards to our current knowledge of SULT1A1 biology, the aforementioned contrary data may reflect the multifunction of SULT1A1 enzyme in the biotransformation of different carcinogens that target different tissues. Moreover, the effect of a low-penetrance susceptibility gene on disease risk is likely to be influenced by modifying genes and environment factors. Thus, the different genetic background and different carcinogen exposure in different populations may to some extent explain the different risk estimates associated with the polymorphism.

The significant association between risk for lung cancer related to smoking and the SULT1A1 A allele, which encodes low activity SULT1A1 (27,32), seems to be puzzling because this enzyme has been shown to be able to activate tobacco smoke-derived carcinogens such as aromatic amines, heterocyclic amines and PAHs (16,1821). However, our current knowledge of bioactivation of these carcinogens by SULT1A1 is mostly obtained from in vitro model studies, which may not all correctly reflect the complicated situation of carcinogen metabolism in vivo. For instance, while sulfonation of PAHs, such as benzo[a]pyrene, and aromatic amines, such as 4-aminobiphenyl, yields reactive metabolites that can form DNA adducts in vitro (16,19,21), the levels of the respective DNA adducts in breast and lung tissues were shown not to be associated with SULT1A1 genotype or activity (41,50). These findings indicate that SULT1A1, among many other metabolic pathways, may not be of importance in the metabolic activation of these carcinogens in vivo. In addition, it should also be borne in mind that tobacco smoke contains numerous carcinogens and the compound(s) that assuredly cause human lung cancer are not well established yet. Our results in the present study and others showing an increased risk of lung cancer associated with the SULT1A1 A allele may suggest that the balance of SULT1A1 activity be in favor of detoxification rather than activation of lung carcinogens presented in tobacco smoke.

However, other possibilities may also exist for the explanation of our results. The association between the SULT1A1 polymorphism and lung cancer risk in a Chinese population might not really relate to the SULT1A1 activity, but instead is secondary to linkage disequilibrium with a yet unidentified, but tightly linked, lung cancer locus. In this case, the polymorphism of SULT1A1 might only serve as a haplotype tag. Alternatively, the effect is polyallelic with several tightly linked polymorphisms influencing lung cancer risk. It could be that the contribution of the SULT1A1 polymorphism to lung cancer risk is influenced positively or negatively by one or more additional polymorphisms within or close to the SULT1A1 gene. Depending on the combination of polymorphic variants, the effect of the SULT1A1 638A allele may be masked due to the presence of other unidentified risk alleles associated with given cancer. This may account for the discrepancy in the role of the SULT1A1 polymorphism in different cancer sites and in different ethnic populations. Further studies would be warranted to address these possibilities.

The frequencies of the variant SULT1A1 allele and genotypes vary markedly with ethnicity. Among Caucasian populations, the A allele frequency was reported to be about 0.30 (2931,3338,41,42) whereas among Africans and African-Americans, the A allele frequency was shown to be about 0.27 (30,31,33). In the present study with 809 healthy controls, we found that the A allele frequency was 0.087 and the AA homozygotes were only 0.3% among Han Chinese, which are much less than those among Caucasians and Africans. Our data are in accordance with those reported previously by Carlini et al. (31) who observed a frequency of 0.086 for the A allele among 290 Chinese women from Shanghai. However, Wu et al. (40) reported a significantly lower frequency of the A allele (0.055) among 308 Chinese males in Taiwan. The low frequency observed by these authors might be because their study subjects were not homogeneous Han Chinese (40). Because of the multifunction of SULT1A1 in the metabolism of endogenous and exogenous compounds and functional significance of the polymorphism, the striking ethnic differences in the SULT1A1 allele frequencies might act as a genetic factor influencing the cancer profiles among different ethnic populations.

The present study may have some limitations because it is a hospital-based, case-control study. Selection bias might occur due to the patients being recruited from only one hospital. However, because we used incident cases and recruited a large number of subjects, our results are unlikely to be attributable to selection bias. The fact that genotype frequencies among controls and cases fit the Hardy–Weinberg law further supports the randomness of subject selection. In addition to tobacco smoking, other factors such as occupational and environmental exposures have been suggested to be associated with lung cancer risk (5,6), and this association might also be modulated by SULT1A1 genotype. Unfortunately, the information on exposures other than smoking is not available in the present study, which prevents more comprehensive evaluation of the role the SULT1A1 polymorphism may play in lung carcinogenesis.

In conclusion, our results, which are against the original hypothesis, demonstrate that the SULT1A1 G638A polymorphism is a genetic susceptibility factor for the development of lung cancer, with the A allele being associated with increased risk of the cancer in Chinese population. This association is especially noteworthy in younger individuals and in smokers and heavy smokers.


    Acknowledgments
 
This work was supported by grants 2002BA711A06 from National 863 High Technology Project, and grants 39825122 and 39990570 from National Natural Science Foundation.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. Yang,L., Parkin,D.M., Li,L. and Chen,Y. (2003) Time trend in cancer mortality in China: 1987–1999. Int. J. Cancer, 106, 771–783.[CrossRef][ISI][Medline]
  2. Chen,Z.M, Xu,Z., Collis,R., Li,W.Y. and Peto,R. (1997) Early health effects of the emerging tobacco epidemic in China. A 16-years prospective study. J. Am. Med. Assoc., 278, 1500–1504.[Abstract]
  3. Peto,R., Lopez,A.D., Boreham,J., Thun,M., Heath,C.,Jr and Doll,R. (1996) Mortality from smoking worldwide. Br. Med. Bull., 52, 12–21.[Abstract]
  4. Kleinerman,R., Wang,Z., Lubin,J., Zhang,S., Metayer,C. and Brenner,A. (2000) Lung cancer and indoor air pollution in rural China. Ann. Epidemiol., 10, 469.
  5. Metayer,C., Wang,Z., Kleinerman,R.A., Wang,L., Brenner,A.V., Cui,H., Cao,J. and Lubin,H. (2002) Cooking oil fumes and risk of lung cancer in women in rural Gansu, China. Lung Cancer, 35, 111–117.[CrossRef][ISI][Medline]
  6. Seow,A., Poh,W.T., The,M., Eng,P., Wang,Y.T., Tan,W.C., Yu,M.C. and Lee,H.P. (2000) Fumes from meat cooking and lung cancer risk in Chinese women. Cancer Epidemiol. Biomarkers Prev., 9, 1215–1221.[Abstract/Free Full Text]
  7. Hecht,S.S. (2002) Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol., 3, 461–469.[CrossRef][ISI][Medline]
  8. Autrup,H. (2000) Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response. Mutat. Res., 464, 65–76.[ISI][Medline]
  9. Bartsch,H., Nair,U., Risch,A., Rojas,M., Wilman,H. and Alexandov,K. (2000) Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol. Biomarkers Prev., 9, 3–28.[Abstract/Free Full Text]
  10. Houlston,R.S. (1999) Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol. Biomarkers Prev., 8, 675–682.[Abstract/Free Full Text]
  11. Lan,Q., He,X., Costa,D.J., Tian,L., Rothman,N., Hu,G. and Muford,J.L. (2000) Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China. Cancer Epidemiol. Biomarkers Prev., 9, 605–608.[Abstract/Free Full Text]
  12. Whyatt,R.M., Bell,D.A., Jedrychowski,W. et al. (1998) Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype. Carcinogenesis, 19, 1389–1392.[Abstract]
  13. Nebert,D.W., Magnus,I.S. and Daly,A.K. (1999) Genetic epidemiology of environmental toxicity and cancer susceptibility: human allelic polymorphisms in drug-metabolizing genes, their functional importance, and nomenclature issues. Drug Metab. Rev., 31, 467–487.[CrossRef][ISI][Medline]
  14. Falany,C.N. (1997) Enzymology of human cytosolic sulfotransferases. FASEB J., 11, 206–216.[Abstract/Free Full Text]
  15. Coughtrie,M.W., Sharp,S., Maxwell,K. and Innes,N.P. (1998) Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem.-Biol. Interact., 109, 3–27.[CrossRef][ISI][Medline]
  16. Banoglu,E. (2000) Current status of the cytosolic sulfotransferases in the metabolic activation of promutagens and procarcinogens. Curr. Drug Metab., 1, 1–30.[ISI][Medline]
  17. Coughtrie,M.W.H. (1996) Sulphation catalysed by the human cytosolic sulphotransferases-chemical defence or molecular terrorism? Hum. Exp. Toxicol., 15, 547–555.[ISI][Medline]
  18. Ozawa,S., Chou,H.C., Kadlubar,F.F., Nagata,K., Yamazoe,Y. and Kato,R. (1994) Activation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine by cDNA-expressed human and rat arylsulfotransferases. Jpn. J. Cancer Res., 85, 1220–1228.[ISI][Medline]
  19. Chou,H.C., Lang,N.P. and Kadlubar,F.F. (1995) Metabolic activation of the N-hydroxy derivative of the carcinogen 4-aminobiphenyl by human tissue sulfotransferases. Carcinogenesis, 16, 413–417.[Abstract]
  20. Watable,T., Ishizuka,T., Isobe,M. and Ozawa,N. (1982) A 7-hydroxymethyl sulfate ester as an active metabolite of 7,12-dimethylbenzo[a]anthracene. Science, 215, 403–405.[ISI][Medline]
  21. Surh,Y.J. and Tannenbaum,S.R. (1995) Sulfotransferase-mediated activation of 7, 8, 9, 10-tetrahydro-7-ol, 7, 8-dihydrodiol, and 7, 8, 9, 10-tetraol derivatives of benzo[a]pyrene. Chem. Res. Toxicol., 8, 693–698.[ISI][Medline]
  22. Arlt,V.M., Glatt,H., Muckel,E., Pabel,U., Sorg,B.L., Schmeiser,H.H. and Phillips,D.H. (2002) Metabolic activation of the environmental contaminant 3-nitrobenzanthrone by human acetyltransferases and sulfotransferase. Carcinogenesis, 23, 1937–1945.[Abstract/Free Full Text]
  23. Willey,J.C., Coy,E., Brolly,C., Utell,M.J, Frampton,M.W., Hammersley,J., Thilly,W.C., Olson,D. and Cairns,K. (1996) Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells. Am. J. Respir. Cell Mol. Biol., 14, 267–272.
  24. Vietri,M., Pietrabissa,A., Mosca,F., Spisni,R. and Pacifici,G.M. (2003) Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues. Xenobiotica, 33, 357–363.[ISI][Medline]
  25. Song,W.C., Qian,Y. and Li,A.P. (1998) Estrogen sulfotransferase expression in the human liver: marked interindividual variation and lack of gender specificity. J. Pharmacol. Exp. Ther., 284, 1197–1202.[Abstract/Free Full Text]
  26. Price,R.A., Spielman,R.S., Lucena,A.L., Van Loon,J.A., Maidak,B.L. and Weinshilboum,R.M. (1989) Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity. Genetics, 122, 905–914.[Abstract/Free Full Text]
  27. Raftogianis,R.B., Wood,T.C., Otterness,D.M., Van Loon,J.A. and Weinshilboum,R.M. (1997) Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem. Biophys. Res. Commun., 239, 398–304.
  28. Adjei,A.A., Prondzinski,J.E, Olson,J.E., Vierkant,R.A., Pankratz,V.S., Fredericksen,Z.S., Sellers,T.A. and Weinshilboum,R.M. (2003) SULT1A1 5'-flanking region polymorphisms and breast cancer risk in the Minesota Breast Cancer Family Study. Proc. Am. Assoc. Cancer Res., 44, 1249.
  29. Ozawa,S., Tang,Y.M., Yamazoe,Y., Kato,R., Lang,N.P. and Kadlubar,F.F. (1998) Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines. Chem.-Biol. Interact., 109, 237–248.[CrossRef][ISI][Medline]
  30. Coughtrie,M.W.H., Gilissen,R.A.H.J., Shek,B., Strange,R.C., Fryer,A.A., Jones,P.W. and Bamber,D.E. (1999) Phenol sulfotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations. Biochem. J., 337, 45–49.[CrossRef][ISI][Medline]
  31. Carlini,E.J., Raftogianis,R.B., Wood,T.C., Jin,F., Zheng,W., Rebbeck,T.R. and Weinshilboum,R.M. (2001) Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. Pharmacogenetics, 11, 57–68.[CrossRef][ISI][Medline]
  32. Ozawa,S., Shimizu,M., Katoh,T., Miyajima,A., Ohno,Y., Matsumoto,Y., Fukuoka,M., Tang,Y.M., Lang,N.P. and Kadlubar,F.F. (1999) Sulfating-activity and stability of cDNA-expressed allozymes of human phenol sulfotransferase, ST1A3*1 (213Arg) and ST1A3*2 (213His), both of which exist in Japanese as well Caucasians. J. Biochem., 126, 271–277.[Abstract]
  33. Nowell,S., Ambrosone,C.B., Ozawa,S., MacLeod,S.L., Mrackova,G., Williams,S., Plaxco,J., Kadlubar,F.F and Lang,N.P. (2000) Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol. Pharmacogenetics, 10, 789–797.[CrossRef][ISI][Medline]
  34. Steiner,M., Bastian,M., Schulz,W.A., Pulte,T., Franke,K.H., Rohring,A., Wolff,J.M., Seiter,H. and Schuff-Werner,P. (2000) Phenol sulfotransferase SULT1A1 polymorphism in prostate cancer: lack of association. Arch. Toxicol., 74, 222–225.[CrossRef][ISI][Medline]
  35. Seth,P., Lunetta,K.L., Bell,D.W. et al. (2000) Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer. Cancer Res., 60, 6859–6863.[Abstract/Free Full Text]
  36. Zheng,W., Xie,D., Cerhan,J.R., Sellers,T.A., Wen,W. and Folsom,A.R. (2001) Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk. Cancer Epidemiol. Biomarkers Prev., 10, 89–94.[Abstract/Free Full Text]
  37. Bamber,D.E., Fryer,A.A., Strange,R.C., Elder,J.B., Deakin,M., Rajagopal,R., Fawole,A., Gilissen,R.A., Campbell,F.C. and Coughtrie,M.W.H. (2001) Phenol sulphotransferase SULT1A1*1 genotype is associated with reduced risk of colorectal cancer. Pharmacogenetics, 11, 679–685.[CrossRef][ISI][Medline]
  38. Wong,C.F., Liyou,N., Leggett,B., Young,J., Johnson,A. and McManus,M.E. (2002) Association of the SULT1A1 R213H polymorphism with colorectal cancer. Clin. Exp. Pharmacol. Physiol., 29, 754–758.[CrossRef][ISI][Medline]
  39. Ozawa,S., Katoh,T., Inatomi,H., Imai,H., Kuroda,Y., Ichiba,M. and Ohno,Y. (2002) Association of genotypes of carcinogen-activating enzymes, phenol sulfotransferase SULT1A1 (ST1A3) and arylamine N-acetyltransferase NAT2, with urothelial cancer in a Japanese population. Int. J. Cancer, 102, 418–421.[CrossRef][ISI][Medline]
  40. Wu,M.-T., Wang,Y.-T., Ho,C.-K., Wu,D.-C., Lee,Y.-C., Hsu,H.-K., Kao,E.-L. and Lee,J.-M. (2003) SULT1A1 polymorphism and esophageal cancer in males. Int. J. Cancer, 103, 101–104.[CrossRef][ISI][Medline]
  41. Tang,D., Rundle,A., Mooney,L., Cho,S., Schnabel,F., Estabrook,A., Kelly,A., Levine,R., Hibshoosh,H. and Perera,F. (2003) Sulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case-control study. Breast Cancer Res. Treat., 78, 217–222.[CrossRef][ISI][Medline]
  42. Wang,Y., Spitz,M.R., Tsou,A.M.-H., Zhang,K., Makan,N. and Wu,X. (2002) Sulfotransferase (SULT) 1A1 polymorphism as a predisposition factor for lung cancer: a case-control analysis. Lung Cancer, 35, 137–142.[CrossRef][ISI][Medline]
  43. Saintot,M., Malaveille,C., Hautefeuille,A. and Gerber,M. (2003) Interactions between genetic polymorphism of cytochrome P450–1B1, sulfotransferase 1A1, catechol-O-methyltransferase and tobacco exposure in breast cancer risk. Int. J. Cancer, 107, 652–657.[CrossRef][ISI][Medline]
  44. Liang,G., Xing,D., Miao,X., Tan,W., Yu,C., Lu,W. and Lin,D. (2003) Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int. J. Cancer, 105, 669–673.[CrossRef][ISI][Medline]
  45. Kleinbaum,D.G., Kupper,L.L. and Morgenstern,H. (1982) Epidemiologic Research: Principles and Quantitative Methods. Lifetime Learning Publications, London.
  46. Nichols,K.E., Malkin,D., Garber,J.E., Fraumeni,J.F.,Jr and Li,F.P. (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancer. Cancer Epidemiol. Biomarkers Prev., 10, 83–87.[Abstract/Free Full Text]
  47. Edwards,S.M., Kote-Jarai,Z., Meitz,J. et al. (2003) Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am. J. Hum. Genet., 72, 1–12.[CrossRef][ISI][Medline]
  48. Denissenko,M.F., Pao,A., Tang,M.-S. and Pfeifer,G.P. (1996) Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspot in p53. Science, 274, 430–432.[Abstract/Free Full Text]
  49. Rundle,A., Tang,D., Hibshoosh,H., Estabrook,A., Schnabel,F., Cao,W., Grumet,S. Della Rocca,A. and Perera,F. (2000) The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer. Carcinogenesis, 21, 1281–1289.[Abstract/Free Full Text]
  50. Culp,S.J., Roberts,D.W., Talaska,G., Lang,N.P., Fu,P.P., Lay,J.O.,Jr, Teitel,C.H., Snawder,J.E., Von Tungeln,L.S. and Kadlubar,F.F. (1997) Immunochemical, 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA adducts in human peripheral lung in relation to metabolic activation pathways involving pulmonary N-oxidation, conjugation, and peroxidation. Mutat. Res., 378, 97–112.[ISI][Medline]
Received October 21, 2003; revised December 4, 2003; accepted December 8, 2003.