To establish a genetic susceptibility assessment model of lung cancer risk potentially associated with polycyclic aromatic hydrocarbon (PAH) inhalation exposure among non-smokers in China, a total of 143 patients with lung adenocarcinoma and 143 cancer-free individuals were recruited. Sixty-eight genetic polymorphisms in 10 pathways related to PAH metabolism and tumorigenesis were selected and examined. It was observed that 3 genetic polymorphisms, along with 10 additional genetic polymorphisms via gene-gene interactions, significantly influenced lung cancer risk potentially associated with PAH inhalation exposure. Most polymorphisms were associated with PAH metabolism. According to the established genetic susceptibility score (GSS), lung cancer risk increased with a rise in the GSS level, thereby indicating a positive dose-response relationship.
Adenocarcinoma ; chemically induced ; epidemiology ; genetics ; Air Pollutants ; toxicity ; China ; Genetic Predisposition to Disease ; Humans ; Inhalation Exposure ; Lung Neoplasms ; chemically induced ; epidemiology ; genetics ; Polycyclic Aromatic Hydrocarbons ; toxicity

AIMTo investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer (PCa) in men from Han, Southern China.

METHODSIn a case-control study of 207 patients with PCa and 235 cancer-free controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms (codons 194, 280 and 399) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method.

RESULTSAmong the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk (adjusted odd ratio [OR]: 1.67, 95% confident interval [CI]: 1.11-2.51), but the XRCC1 Arg194Trp variant allele had a 38% reduction in risk of PCa (adjusted OR: 0.62, 95% CI: 0.41-0.93). However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa (adjusted OR: 4.31; 95% CI: 1.24-14.99) than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers (adjusted OR: 2.04; 95% CI: 1.03-4.05).

CONCLUSIONThese results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.

Adenocarcinoma ; blood ; epidemiology ; genetics ; Aged ; China ; epidemiology ; DNA-Binding Proteins ; blood ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Odds Ratio ; Polymorphism, Restriction Fragment Length ; Prostatic Neoplasms ; blood ; epidemiology ; genetics ; Risk Factors ; Seroepidemiologic Studies ; X-ray Repair Cross Complementing Protein 1

Adenocarcinoma, Follicular ; epidemiology ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Genes, ras ; genetics ; Humans ; Point Mutation ; Prognosis ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; epidemiology ; genetics ; metabolism ; pathology ; Transcription Factors

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.
Adenocarcinoma/epidemiology/*genetics ; Case-Control Studies ; Female ; Gene Frequency/genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/epidemiology/*genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/*genetics ; Promoter Regions, Genetic/*genetics ; Republic of Korea/epidemiology ; Telomerase/*genetics ; Telomere/physiology ; Telomere Homeostasis/*genetics

BACKGROUND: Although there have been some reports on microsatellite alterations in gastric cancer, findings are inconsistent regarding the associations between histological classification and microsatellite instability (MSI). In the present study, we attempted to determine whether Lauren's histological subtypes are related with MSI status. METHODS: Paraffin-embedded tissue samples from 14 diffuse-type and 14 intestinal-type gastric adenocarcinomas were matched up according to patient gender and age. Mononucleotide markers (BAT25 and BAT26) and dinucleotide markers (D2S123, D5S346, and D17S250) were used for MSI analyses. Microsatellite genotypes were categorized in terms of high MSI incidence (MSI-H, > 30% positive marker) or low MSI incidence (MSI-L, < 30% positive marker). Losses of hMLH1 and hMSH2 protein expression were immunohistochemically studied. RESULTS: MSI-H was observed in 11 cases (78%) of the 14 intestinal-type cases as compared to 3 (21%) of the 14 diffuse-type cases (p=0.007). In MSI-H tumors, 10 cases (71%) showed losses of hMLH1 protein expression, while 2 cases (14%) in MSI-L tumors showed losses of hMLH1 protein expression (p=0.006). CONCLUSION: MSI-H tumors are more frequently found in intestinal-type gastric cancer, which suggests the possibility that there are different pathogenic pathways in gastric carcinogenesis according to histologic type.
Adenocarcinoma/epidemiology/*genetics/pathology ; Aged ; Base Pair Mismatch/*genetics ; Comparative Study ; Female ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Incidence ; Korea/epidemiology ; Male ; Microsatellite Repeats/*genetics ; Neoplasm Proteins/genetics ; Nuclear Proteins/genetics ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Retrospective Studies ; Stomach Neoplasms/epidemiology/*genetics/pathology

BACKGROUNDIn China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.

METHODSThe percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.

RESULTSA positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P < 0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P < 0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P < 0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P < 0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥ 50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.

CONCLUSIONSThe proportion of familial cancer in upper gastrointestinal carcinomas decreases by the primary site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Adenocarcinoma ; genetics ; Age of Onset ; Carcinoma, Squamous Cell ; genetics ; Cardia ; China ; Esophageal Neoplasms ; genetics ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; epidemiology ; Risk Factors ; Stomach Neoplasms ; genetics

OBJECTIVETo characterize the profiles of chromosome imbalance in esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the high incidence area in Henan.

METHODSChromosomal aberrations of 37 samples of SCC and 30 GCA were analyzed by comparative genomic hybridization comparative genomic hybridization (CGH).

RESULTSIt was found that the most frequently detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and 7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%), and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p (57%), and followed by 19p, 1p and 4p.

CONCLUSIONThe present findings demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance in GCA, which provide important theoretic information for identifying and cloning novel SCC/GCA-related genes.

Adenocarcinoma ; genetics ; Carcinoma, Squamous Cell ; epidemiology ; genetics ; Cardia ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 20 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; genetics ; Esophageal Neoplasms ; epidemiology ; genetics ; Gene Amplification ; Gene Deletion ; Humans ; Nucleic Acid Hybridization ; methods ; Stomach Neoplasms ; epidemiology ; genetics

OBJECTIVEThe aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens.

METHODS287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides.

RESULTSTumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⁺ group and 2 months in the ARMS⁻ group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⁺ group and 7 months in the ARMS⁻ group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⁺ and Seq⁻ groups (P = 0.227, P = 0.510, respectively), and Seq⁺/ARMS⁺ and Seq⁻/ARMS⁺ groups (P = 0.354, P = 0.334, respectively).

CONCLUSIONSThe detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.

Adenocarcinoma ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Humans ; Lung Neoplasms ; diagnosis ; epidemiology ; metabolism ; Mutation ; Mutation Rate ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; genetics ; metabolism

Lung cancer is the leading cause of cancer death worldwide, with large variation of the incidence and mortality across regions. Although the mortality of lung cancer has been decreasing, or steady in the US, it has been increasing in Asia for the past two decades. Smoking is the leading cause of lung cancer, and other risk factors such as indoor coal burning, cooking fumes, and infections may play important roles in the development of lung cancer among Asian never smoking women. The median age of diagnosis in Asian patients with lung cancer is generally younger than Caucasian patients, particularly among never-smokers. Asians and Caucasians may have different genetic susceptibilities to lung cancer, as evidenced from candidate polymorphisms and genome-wide association studies. Recent epidemiologic studies and clinical trials have shown consistently that Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer (NSCLC), independent of smoking status. Compared with Caucasian patients with NSCLC, East Asian patients have a much higher prevalence of epidermal growth factor receptor (EGFR) mutation (approximately 30% vs. 7%, predominantly among patients with adenocarcinoma and never-smokers), a lower prevalence of K-Ras mutation (less than 10% vs. 18%, predominantly among patients with adenocarcinoma and smokers), and higher proportion of patients who are responsive to EGFR tyrosine kinase inhibitors. The ethnic differences in epidemiology and clinical behaviors should be taken into account when conducting global clinical trials that include different ethnic populations.
Adenocarcinoma ; ethnology ; genetics ; metabolism ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Non-Small-Cell Lung ; ethnology ; genetics ; metabolism ; European Continental Ancestry Group ; genetics ; Far East ; epidemiology ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms ; ethnology ; genetics ; metabolism ; Mutation ; Oncogene Proteins, Fusion ; metabolism ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Risk Factors ; Smoking ; adverse effects ; United States ; epidemiology ; ras Proteins ; genetics ; metabolism

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.
Adenocarcinoma in Situ/epidemiology* ; Adult ; Aged ; Aged, 80 and over ; Female ; Human papillomavirus 16/genetics* ; Human papillomavirus 18/genetics* ; Humans ; Middle Aged ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Prevalence ; Uterine Cervical Neoplasms/pathology* ; Young Adult