共查询到20条相似文献,搜索用时 31 毫秒
1.
Katsumata K Sumi T Tomioka H Aoki T Koyanagi Y 《International journal of clinical oncology / Japan Society of Clinical Oncology》2003,8(6):352-356
Background We investigated the influence of genes on the apoptosis of colorectal tumor cells, based on DNA and mRNA kinetics.Methods In 30 colorectal cancer patients, we examined the mRNA expression of p53, bax, bcl-2, and p21
WAF1
, and we also investigated the development of tumor cell apoptosis, using a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method.Results TUNEL-positive cells showed a positive correlation with bax (P = 0.010) and a negative correlation with p21 (P = 0.04). We also investigated the relationship between p53 point mutation, p21 immunostaining degree, and apoptosis, based on DNA ladder expression. A remarkable correlation (P = 0.0090) was found between p21 and apoptosis.Conclusions The present study findings suggest that tumor cell apoptosis is (1) strongly inhibited by p21, (2) induced by bax, and (3) influenced by bcl-2, which, presumably, inhibits tumor cell apoptosis. 相似文献
2.
3.
Ming Wu Shuho Semba Naohide Oue Nobunao Ikehara Wataru Yasui Hiroshi Yokozaki 《Gastric cancer》2004,7(4):246-253
Background The BRAF and K-ras genes are the most frequently mutated oncogenes in various human malignancies. We examined BRAF and K-ras mutations in human gastric cancer, and investigated their relationship with microsatellite instability (MSI) and the hypermethylation of promoter regions in hMLH1 and O
6
-methylguanine DNA methyltransferase (MGMT).Methods Sixteen gastric cancer cell lines and 62 gastric cancer tissue samples were screened for BRAF and K-ras mutations by direct sequencing. We also performed a microsatellite assay and investigated methylation status in the promoter regions of hMLH1 and MGMT.Results mutation was not found in any of the cancer cell lines examined. One (1.6%) cancer tissue sample showed a point mutation in the BRAF gene (GT_G GA_G; V599E). K-ras mutation (GG_T GA_T, G12D) was detected in five (31%) gastric cancer cell lines and in 1 (1.6%) gastric cancer tissue sample. In the gastric cancer tissue samples examined, MSI was detected in 23 (37%) samples. Hypermethylated promoter regions in hMLH1 and MGMT, respectively, were detected in 6 (10%) and 13 (21%) gastric cancer tissue samples. Microsatellite stable (MSS) tumors showed frequent lymphatic invasion (P = 0.050).Conclusion Although BRAF mutation has been reported in a variety of other human cancers, it is a rare event in the carcinogenesis and progression/development of gastric cancer. 相似文献
4.
Scrideli CA Carlotti CG Mata JF Neder L Machado HR Oba-Sinjo SM Rosemberg S Marie SK Tone LG 《Journal of neuro-oncology》2007,83(3):233-239
Overexpression of the EGFR, IGFBP-2 and HIF-2A genes has been observed in high-grade astrocytomas and these genes seem to be functionally related to one another. This study
aimed to define the profile of their expressions, interactions and correlation with clinical features and prognostic significance
in microdissected tumor samples from 84 patients with astrocytomas of different grades and from 6 white matter non-neoplasic
brain tissue sample. EGFR, IGFBP-2 and HIF-2A gene expression levels were analyzed by quantitative real-time PCR and differed significantly between grades I–IV astrocytic
tumors (P < 0.0001, P < 0.0001 and P: 0.0013, respectively) when analyzed by the Kruskal–Wallis test. Grade I astrocytomas presented gene expression levels similar
to those encountered in samples of microdissected white matter of non-neoplastic brain tissue Overexpression of the EGFR, IGFBP-2 and HIF-2A genes was significantly associated with lower 2-year survival (P: 0.009, P: 0.0002 and P: 0.008, respectively). Co-overexpression of these genes was strongly associated with high-grade gliomas and lower survival
in univariate (P < 0.0001) and multivariate (P: 0.009) analysis, suggesting that the co-expression of the EGFR/IGFBP-2/HIF-2A pathway genes may have a more important clinical and biological impact than the expression of each individual gene alone.
These data support the existence of a common pathway involving these genes that could contribute to the design of new target
treatments. 相似文献
5.
Takafumi Kubo Hiromasa Yamamoto Koichi Ichimura Masaru Jida Tatsuro Hayashi Hiroki Otani Kazunori Tsukuda Yoshifumi Sano Katsuyuki Kiura Shinichi Toyooka 《Lung cancer (Amsterdam, Netherlands)》2009,65(3):328-332
We examined the methylation status in 100 specimens of lung adenocarcinomas measuring 2 cm or less and with bronchioloalveolar carcinoma (BAC) components (Noguchi types A–C) and then compared the methylation status between noninvasive tumors (Noguchi type A or B) and invasive tumors (Noguchi type C). Methylation-specific PCR was used to determine the methylation statuses of p16INK4a, RASSF1A, CDH13, RARβ, and Cyclin D2. The methylation index that was regarded as representing the degree of methylation was calculated. We also determined the mutational statuses of EGFR exons 19 and 21 using a PCR-based method. A multivariate analysis showed that the aberrant methylation of p16INK4a, RASSF1A, and CDH13 was significantly more frequent in invasive tumors than in noninvasive tumors [p16INK4a, 36.5% versus (vs.) 8.3%, P = 0.0023; RASSF1A, 46.2% vs. 14.6%, P = 0.0012; CDH13, 42.3% vs. 10.4%, P = 0.0006]. The methylation index was significantly higher in invasive tumors than in noninvasive tumors (P = 0.004). The methylation of p16INK4a was significantly more frequent in EGFR wild-type tumors than in EGFR mutant tumors (P = 0.021). Our results indicate the involvement of epigenetic alterations in the progression of adenocarcinoma with BAC components. 相似文献
6.
The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated
with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast and ovarian cancer, DNA-mismatch repair (MMR) genes associated hereditary non polyposis colorectal cancer
and CDKN2A associated familial malignant melanoma are very little studied. Herein we report the prevalence of childhood tumors (diagnosed
≤18 years of age) in families identified with mutation in the BRCA1/2, MMR and CDKN2A genes. Using pedigrees at the Regional Oncogenetic Clinic at Lund University Hospital, the prevalence of childhood cancer
was estimated in families with mutations in the BRCA1 (n = 98), BRCA2 (n = 43) MMR (MLH1, MSH2 MSH6) (n = 31) and CDKN2A (n = 15) genes in comparison with population based control families (n = 854). Compared with the control group, a significantly higher prevalence of childhood cancer was found in families with
mutations in BRCA2 (9.3% vs. 0.8% P = 0.001), MMR genes (19.4% vs. 0.8% P < 0.001) and CDKN2A (20.0% vs. 0.8% P < 0.001), but not in families with BRCA1 mutations (1.0% vs. 0.8% P = 0.6). Further analyses showed an increased risk for childhood tumors in families with mutations in BRCA2 (OR 12.4; 95% CI 3.5–44.1), MMR genes (OR 29.0; 95% CI 9.1–92.6), and CDKN2A (OR 30.2; 95% CI 7.0–131.1). This study suggests that the risk for childhood tumors is increased in families with germline
mutations in the BRCA2, MMR and CDKN2A genes. 相似文献
7.
8.
Slattery ML Sweeney C Wolff R Herrick J Baumgartner K Giuliano A Byers T 《Breast cancer research and treatment》2007,104(2):197-209
Background An insulin-related pathway to breast cancer has been hypothesized.
Methods We examine the 19 CA repeat of the IGF1 gene, the -202 C > A IGFBP3, the G972R IRS, and the G1057D IRS2 polymorphisms among 1,175 non-Hispanic white (NHW) and 576 Hispanic newly diagnosed breast cancer cases and 1,330 NHW and
727 Hispanic controls living in Arizona, Colorado, New Mexico, and Utah.
Results Among post-menopausal women not recently exposed to hormones, not having the 19 CA repeat of IGF1 gene was associated with breast cancer among NHW women [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.21–3.79] and
having an R allele of G972R IRS1 increased breast cancer risk among Hispanic women (OR 2.70, 95% CI 1.13–6.46). Among post-menopausal Hispanic women recently
exposed to hormones the A allele of the -202 C > A IGFBP3 polymorphism increased risk of breast cancer (OR 1.57, 95% CI 1.06–2.33). The IGF1 19 CA repeat polymorphism interacted with hormone replacement therapy (HRT) among NHW post-menopausal women; women who had
the 19/19 IGF1 genotype were at reduced risk of breast cancer (OR 0.64, 95% CI 0.47–0.88) if they did not use HRT. We also observed interaction
between body mass index and IGF1 19 CA repeat (p=0.06) and between weight gain and the -202 C > A IGFBP3 polymorphism (p=0.05) in NHW post-menopausal women not recently exposed to hormones.
Conclusions Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern
United States may be dependent on estrogen exposure and may differ by ethnicity. 相似文献
9.
Hansen Tv Jønson L Albrechtsen A Andersen MK Ejlertsen B Nielsen FC 《Breast cancer research and treatment》2009,115(2):315-323
BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0–36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian cancer patients in whom a deleterious mutation in BRCA1 and BRCA2 was not detected by sequencing using the multiplex ligation-dependent probe amplification (MLPA) assay. We identified 15
patients with 7 different genomic rearrangements, including a BRCA1 exon 5–7 deletion with a novel breakpoint, a BRCA1 exon 13 duplication, a BRCA1 exon 17–19 deletion, a BRCA1 exon 3–16 deletion, and a BRCA2 exon 20 deletion with a novel breakpoint as well as two novel BRCA1 exon 17–18 and BRCA1 exon 19 deletions. The large rearrangements in BRCA1 and BRCA2 accounted for 9.2% (15/163) of all BRCA1 and BRCA2 mutations in East Denmark. Nine patients had the exon 3–16 deletion in BRCA1. By SNP analysis we find that the patients share a 5 Mb fragment of chromosome 17, including BRCA1, indicating that the exon 3–16 deletion represents a Danish founder mutation.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
Hanifa Bouzourene Pierre Hutter Lorena Losi Patricia Martin Jean Benhattar 《Familial cancer》2010,9(2):167-172
Lynch syndrome is one of the most common hereditary colorectal cancer (CRC) syndrome and is caused by germline mutations of
MLH1, MSH2 and more rarely MSH6, PMS2, MLH3 genes. Whereas the absence of MSH2 protein is predictive of Lynch syndrome, it is not the case for the absence of MLH1 protein.
The purpose of this study was to develop a sensitive and cost effective algorithm to select Lynch syndrome cases among patients
with MLH1 immunohistochemical silencing. Eleven sporadic CRC and 16 Lynch syndrome cases with MLH1 protein abnormalities were
selected. The BRAF c.1799T> A mutation (p.Val600Glu) was analyzed by direct sequencing after PCR amplification of exon 15. Methylation of MLH1 promoter was determined by Methylation-Sensitive Single-Strand Conformation Analysis. In patients with Lynch syndrome, there
was no BRAF mutation and only one case showed MLH1 methylation (6%). In sporadic CRC, all cases were MLH1 methylated (100%) and 8 out of 11 cases carried the above BRAF mutation (73%) whereas only 3 cases were BRAF wild type (27%). We propose the following algorithm: (1) no further molecular analysis should be performed for CRC exhibiting
MLH1 methylation and BRAF mutation, and these cases should be considered as sporadic CRC; (2) CRC with unmethylated MLH1 and negative for BRAF mutation should be considered as Lynch syndrome; and (3) only a small fraction of CRC with MLH1 promoter methylation but negative for BRAF mutation should be true Lynch syndrome patients. These potentially Lynch syndrome patients should be offered genetic counselling
before searching for MLH1 gene mutations. 相似文献
11.
Tatiana A Ivanova Daria A Golovina Larisa E Zavalishina Galina M Volgareva Alexey N Katargin Yulia Y Andreeva Georgy A Frank Fjodor L Kisseljov Natalia P Kisseljova 《BMC cancer》2007,7(1):47
Background
High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas 相似文献12.
Eun-Hui Jeong Tae-Gul Lee Yun Jung Ko Seo Yun Kim Hye-Ryoun Kim Hyunggee Kim Cheol Hyeon Kim 《Cellular oncology (Dordrecht)》2018,41(6):663-675
Background
Squamous cell lung cancer (SqCLC) is a distinct histologic subtype of non-small cell lung cancer (NSCLC). Although the discovery of driver mutations and their targeted drugs has remarkably improved the treatment outcomes for lung adenocarcinoma, currently no such molecular target is clinically available for SqCLC. The CDKN2A locus at 9p21 encodes two alternatively spliced proteins, p16INK4a (p16) and p14ARF (p14), which function as cell cycle inhibitors. The Cancer Genome Atlas (TCGA) project revealed that CDKN2A is inactivated in 72% of SqCLC cases. In addition, it was found that CDKN2A mutations are significantly more common in SqCLC than in adenocarcinoma. Down-regulation of p16 and p14 by CDKN2A gene inactivation leads to activation of cyclin-dependent kinases (CDKs), thereby permitting constitutive phosphorylation of Rb and subsequent cell cycle progression. Here, we hypothesized that CDK inhibition may serve as an attractive strategy for the treatment of CDKN2A-defective SqCLC.Methods
We investigated whether the CDK inhibitors flavopiridol and dinaciclib may exhibit antitumor activity in CDKN2A-defective SqCLC cells compared to control cells. The cytotoxic effect of the CDK inhibitors was evaluated using cell viability assays, and the induction of apoptosis was assessed using TUNEL assays and Western blot analyses. Finally, anti-tumor effects of the CDK inhibitors on xenografted cells were investigated in vivo.Results
We found that flavopiridol and dinaciclib induced cytotoxicity by enhancing apoptosis in CDKN2A-defective SqCLC cells, and that epithelial to mesenchymal transition (EMT) decreased and autophagy increased during this process. In addition, we found that autophagy had a cytoprotective role.Conclusion
Our data suggest a potential role of CDK inhibitors in managing CDKN2A-defective SqCLC.13.
The identification of clinical subsets of glioblastomas (GBM) associated with different molecular genetic profiles had opened the possibility to design tailored therapies to individual patients. One of the most intrigued subtypes is the long-term survival (LTS) GBM, which responds better to current therapies. The present investigation on GBM from 50 consecutive GBM displaying classic survival and seven LTS GBM is based on molecular epigenetic, clinical and histopathological analyses. Our aim was to recognize biomarkers useful to distinguish LTS from classic GBM. We analyzed the promoter methylation status of key regulator genes implicated in tumor invasion (TIMP2, TIMP3), apoptosis and inflammation (TMS1/ASC, DAPK) as well as overall survival, therapy status and tumor pathological features. For the first purpose a methylation-specific PCR approach was performed to analyze the CpG island promoter methylation status of each gene. The overall TMS1/ASC methylation rate in the 57 analyzed tumors was 21.05%. Hypermethylation of TMS1/ASC was significantly more frequent in LTS GBM (57.1% vs. 16%, P=0.029, Fisher's exact test). DAPK promoter hypermethylation was only observed in the LTS subset (14.3%) whereas TIMP2 and TIMP3 were unmethylated in both GBM collectives. Our results strongly suggest that, compared to classic GBM, LTS GBM display distinct epigenetic characteristics which might provide additional prognostic biomarkers for the assessment of this malignancy. 相似文献
14.
Chih-Yi Hsu Hsiang-Ling Ho Yi-Chun Chang-Chien Yi-Wen Chang Donald Ming-Tak Ho 《Journal of neuro-oncology》2015,123(3):459-464
O6–methylguanine–DNA–methyltransferase (MGMT) is mainly regulated by cytosine–guanine island promoter methylation that is believed to occur only in neoplastic tissue. The present study was undertaken to investigate whether methylation occurs also in non-neoplastic brains by collecting 45 non-neoplastic brains from autopsies and 56 lobectomy specimens from epileptic surgeries. The promoter methylation status of MGMT was studied by methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ), while protein expression was studied by immunohistochemical stain (IHC). The methylation rates, as determined by MSP and PSQ, were 3.0 % (3/101) and 2.9 % (2/69), respectively. Of note, no case had positive result concomitantly from both MSP and PSQ (3 were MSP+/PSQ? and 2 were MSP?/PSQ+), and all the positive samples were further confirmed by cloning and Sanger sequencing. All the methylated cases, except for those having indeterminate IHC results from autopsy specimens, revealed no loss of MGMT protein expression and similar staining pattern to that of the unmethylated cases. In conclusion, the current study demonstrated that MGMT promoter methylation could occur in a low percentage of non-neoplastic brains but did not affect the status of protein expression, which could be regarded as a normal variation in non-neoplastic brains. 相似文献
15.
Edneia AS Ramos Anamaria A Camargo Karin Braun Renata Slowik Iglenir J Cavalli Enilze MSF Ribeiro Fábio de O Pedrosa Emanuel M de Souza Fabrício F Costa Giseli Klassen 《BMC cancer》2010,10(1):23
Background
CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. CXCL12 promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (ESR1) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the CXCL12 promoter and ESR1 in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data. 相似文献16.
Choi DH Cho DY Lee MH Park HS Ahn SH Son BH Haffty BG 《Breast cancer research and treatment》2008,112(3):569-573
The germline CHEK2 1100delC mutation is a low penetrance breast cancer susceptibility allele, frequently observed in patient with family history
of breast cancer and/or young age and the frequency varied according to race or ethnicity. In this study, we evaluated the
significance of CHEK2 1100delC in predisposition to breast cancer by assessing its frequency in a material of 493 Korean breast cancer patients
who had been screened for BRCA1 and BRCA2 mutations (42 patients had deleterious mutation of BRCA1/2). Mutation detection of CHEK2 1100delC was based upon analysis of primer extension products generated for previously amplified genomic DNA using a chip
based MALDI-TOP mass spectrometry platform. After overall measurement automatically, assays which had bad peaks were checked
again manually. None of the 493 Korean patients with breast cancer who were candidate for BRCA1 and BRCA2 test carried the 1100delC mutation observed in Caucasians with limited frequency. In the previous studies, we observed higher
or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasian breast cancer population. In the present study, we
evaluated the role of a CHEK2 1100delC as a susceptibility mutation of breast cancer in the Korean population. However, our results suggest that this mutation
is absent or may be very infrequent in Korean patients with breast cancer who have high risk of BRCA1 and BRCA2 mutation, making its screening irrelevant from the practical point view. 相似文献
17.
Satoru Moriyama Yoshiaki Nakashima Motoki Yano Masahiro Kaji Yosuke Yamakawa Tatsuya Toyama Hiroko Yamashita Hirotaka Iwase Hidefumi Sasaki Yushi Saito Masanobu Kiriyama Jyoji Kato Yoshitaka Fujii 《Cancer science》2002,93(7):783-788
The CDKN2 gene is located on the short arm of chromosome 9p and encodes two unrelated proteins, p16INK4a and p14ARF, through the use of independent first exons and shared exons 2 and 3. p16INK4a is a cyclin‐dependent kinase inhibitor, whereas p14ARF regulates the cell cycle through a p53 and MDM2–dependent pathway. We have examined the expression of p16INK4a and p14ARF using competitive RT‐PCR in 60 non‐small cell lung cancers (NSCLCs) and matching normal lung tissues. The intensities of bands for p16INK4a and p14ARF were nearly equal or the intensity of the p16INK4a band slightly exceeded that of p14ARF in the normal lung tissues (n=60). In 38 tumors the intensity of the p16INK4a band was similar to or slightly weaker than that of p14ARF. In 6 tumors the intensity of the p16INK4a band was weaker than that of p14ARF. In 15 tumors the intensity of the p14ARF band was very strong and the p16INK4a band was barely visible. In only one tumor was the intensity of the p16INK4a band very strong, while the band of p14ARF was barely visible. The ratio of the intensity of p16INK4a to p14ARF had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II‐IV tumors had significantly lower p16INK4a to p14ARF ratios than the p stage I tumors (P=0.036). The T2–4 tumors had significantly lower p16INK4a to p14ARF ratios than the T1 tumors (P=0.005). The N1–3 tumors had significantly lower p16INK4a to p14ARF ratios than the NO tumors (P=0.014). Our results suggest that the ratio of expression of p16INK4a to p14ARFtends to decrease during the progression of NSCLC. 相似文献
18.
Promoter methylation pattern of caspase-8, P16INK4A,MGMT, TIMP-3, and E-cadherin in medulloblastoma 总被引:5,自引:0,他引:5
Methylation of promoter regions of CpG-rich sites is an important mechanism for silencing of tumor suppressor genes (TSG).
To evaluate the role of tumor suppressor genes caspase-8 (CASP8), TIMP-3, E-cadherin (CDH1), p16INK4A, and MGMT in medulloblastoma tumorigenesis, 51 medulloblastomas (46 primary tumor specimens, 5 cell lines) were screened
for methylation of promoter linked CpG-islands. For CASP8, we examined the 5′ UTR region that has been shown to be associated
with expression of CASP8. As detected by methylation specific PCR, methylation rate was low for TIMP-3 (3% of tumor samples;
1/5 cell lines), for MGMT (0% of tumor samples; 1/5 cell lines), for p16INK4A (2% of tumor samples; 2/5 cell lines) and for CDH1 (8% of tumor samples; 1/4 cell lines). CASP8, however, was methylated
in 90% of tumor samples and 4/5 cell lines examined. Screening other tumor entities for CASP8 methylation, we found a similarly
high level in 6 neuroblastoma cell lines in contrast to 5 osteosarcoma-, 4 Ewing’s sarcoma-and 6 non-embryonic tumor cell
lines without any increased promoter methylation. From our results we conclude that methylation of the CASP8 5′ UTR region
may play a role in inactivation of CASP8 in neural crest tumors. 相似文献
19.
Slattery ML Curtin K Giuliano AR Sweeney C Baumgartner R Edwards S Wolff RK Baumgartner KB Byers T 《Breast cancer research and treatment》2008,109(1):101-111
We evaluated the association between smoking and risk of breast cancer in non-Hispanic white (NHW) and Hispanic or American
Indian (HAI) women living in the Southwestern United States. Data on lifetime exposure to active and passive smoke data were
available from 1527 NHW cases and 1601 NHW controls; 798 HAI cases and 924 HAI controls. Interleukin 6 (IL6) and Estrogen Receptor alpha (ESR1) polymorphisms were assessed in conjunction with smoking. Pack-years of smoking (≥15) were associated with increased risk
of pre-menopausal breast cancer among NHW women (OR 1.6, 95% CI 1.1–2. 4). Passive smoke increased risk of pre-menopausal
breast cancer for HAI women (OR 1.9, 95% CI 1.1–3.1 everyone; OR 2.3, 95% CI 1.2–4.5 nonsmokers). HAI pre-menopausal women
who were exposed to 10+ h of passive smoke per week and had the rs2069832 IL6 GG genotype had over a fourfold increased risk of breast cancer (OR 4.4, 95% CI 1.5–12.8; P for interaction 0.01). Those with the ESR1 Xba1 AA genotype had a threefold increased risk of breast cancer if they smoked ≥15 pack-years relative to non-smokers (P interaction 0.01). These data suggest that breast cancer risk is associated with active and passive smoking. 相似文献