Overall and cause-specific mortality rates among men and women with high exposure to indoor air pollution from the use of smoky and smokeless coal: a cohort study in Xuanwei, China.

OBJECTIVES: Never-smoking women in Xuanwei (XW), China, have some of the highest lung cancer rates in the country. This has been attributed to the combustion of smoky coal used for indoor cooking and heating. The aim of this study was to evaluate the spectrum of cause-specific mortality in this unique population, including among those who use smokeless coal, considered 'cleaner' coal in XW, as this has not been well-characterised. DESIGN: Cohort study. SETTING: XW, a rural region of China where residents routinely burn coal for indoor cooking and heating. PARTICIPANTS: Age-adjusted, cause-specific mortality rates between 1976 and 2011 were calculated and compared among lifetime smoky and smokeless coal users in a cohort of 42 420 men and women from XW. Mortality rates for XW women were compared with those for a cohort of predominately never-smoking women in Shanghai. RESULTS: Mortality in smoky coal users was driven by cancer (41%), with lung cancer accounting for 88% of cancer deaths. In contrast, cardiovascular disease (CVD) accounted for 32% of deaths among smokeless coal users, with 7% of deaths from cancer. Total cancer mortality was four times higher among smoky coal users relative to smokeless coal users, particularly for lung cancer (standardised rate ratio (SRR)=17.6). Smokeless coal users had higher mortality rates of CVD (SRR=2.9) and pneumonia (SRR=2.5) compared with smoky coal users. These patterns were similar in men and women, even though XW women rarely smoked cigarettes. Women in XW, regardless of coal type used, had over a threefold higher rate of overall mortality, and most cause-specific outcomes were elevated compared with women in Shanghai. CONCLUSIONS: Cause-specific mortality burden differs in XW based on the lifetime use of different coal types. These observations provide evidence that eliminating all coal use for indoor cooking and heating is an important next step in improving public health particularly in developing countries.

Cigarette smoking and oral microbiota in low-income and African-American populations.

BACKGROUND: Cigarette smoking is a common risk factor for diseases and cancers. Oral microbiota is also associated with diseases and cancers. However, little is known about the impact of cigarette smoking on the oral microbiota, especially among ethnic minority populations. METHODS: We investigated cigarette smoking in relationship with the oral microbiota in a large population of predominately low-income and African-American participants. Mouth rinse samples were collected from 1616 participants within the Southern Community Cohort Study, including 592 current-smokers, 477 former-smokers and 547 never-smokers. Oral microbiota was profiled by 16S ribosomal RNA gene deep sequencing. RESULTS: Current-smokers showed a different overall microbial composition from former-smokers (p=6.62×10-7) and never-smokers (p=6.00×10-8). The two probiotic genera, Bifidobacterium and Lactobacillus, were enriched among current-smokers when compared with never-smokers, with Bonferroni-corrected p values (PBonferroni ) of 1.28×10-4 and 5.89×10-7, respectively. The phylum Actinobacteria was also enriched in current-smokers when compared with never-smokers, with a median relative abundance of 12.35% versus 9.36%, respectively, and with a PBonferroni =9.11×10-11. In contrast, the phylum Proteobacteria was depleted in current smokers (PBonferroni =5.57×10-13), with the relative abundance being almost three times that of never-smokers (7.22%) when compared with that of current-smokers (2.47%). Multiple taxa within these two phyla showed differences in abundance/prevalence between current-smokers and never-smokers at PBonferroni <0.05. The differences in the overall microbial composition and abundance/prevalence of most taxa were observed among both African-Americans and European-Americans. Meanwhile, such differences were not observed between former-smokers and never-smokers. CONCLUSION: Smoking has strong impacts on oral microbial community, which was recovered after smoking cessation.

Impact of known risk factors on endometrial cancer burden in Chinese women.

This study aimed to provide data on the impact of known risk factors on endometrial cancer burden. Using data on 1199 endometrial cancer cases and 1212 frequency matched controls from a population-based case-control study carried out in urban Shanghai, China from 1997 to 2003, multivariable adjusted odds ratios were obtained from unconditional logistic regression analyses. Partial population-attributable risks were calculated and corresponding 95% confidence intervals were estimated using a bootstrap method. An estimated 16.94% of endometrial cancer cases were attributed to overweight or obesity; 8.39% to meat intake; 5.45% to nonregular tea drinking; 5.23% to physical inactivity; and 1.77% to family history of endometrial, breast, or colorectal cancers. Overall, these risk factors accounted for 36.01% (95% confidence interval: 28.55-43.11%) of total endometrial cancer cases. Similar results were observed when analysis was restricted to postmenopausal women. Among modifiable lifestyle factors, overweight and obesity accounted for the largest proportion of endometrial cancer in the study population. Lifestyle alterations, such as maintenance of healthy weight, regular exercise, consumption of less meat, and tea drinking, could potentially reduce endometrial cancer by more than one-third.

[A case-control study on genetic polymorphism of CYP17 MspA(1)I and its association with endometrial cancer risk].

OBJECTIVE: To assess whether the polymorphisms of CYP17 MspA(1)I are associated with the susceptibility of endometrial cancer. METHODS: The allelic discrimination of the CYP17A1 gene polymorphisms were assessed with the ABI PRISM 7900 Sequence Detection Systems using TaqMan genotyping assay. Unconditional logistic regression was applied to assess odds ratio and 95% CI and evaluate the association between different genotypes and endometrial cancer development. RESULTS: The frequencies of wild-type, heterozygote and homozygote for the CYP17 MspA(1)I in control women in Shanghai were 17.8%, 49.3% and 32.9%, respectively. No significant difference was found in the distribution of various genotypes of CYP17 MspA(1)I between patients and controls. Pregnancy was associated with reduced risk of endometrial cancer in pre-menopausal women with A2 allele, OR = 0.66, 95% CI: 0.44 approximately 0.99. In post-menopausal women with A2 allele, more pregnancies ( > 2) and shorter time of menstruation ( < or = 32 yrs) were associated with reduced risk of endometrial cancer. CONCLUSION: No significant relationship was found between CYP17 MspA(1)I genotypes and endometrial cancer risk.

Modifying effects of sulfotransferase 1A1 gene polymorphism on the association of breast cancer risk with body mass index or endogenous steroid hormones.

Sulfotransferase (SULT) 1A1 is involved in the inactivation and elimination of estrogens and catechol estrogens. A common functional polymorphism (Arg213His) has been linked in our previous study of postmenopausal Caucasian women to an elevated risk of breast cancer and the association appeared to be modified by factors related to high endogenous estrogen exposures. We further evaluated this polymorphism and levels of BMI and steroid hormones in association with breast cancer risk in a population-based case-control study of Chinese women, involving 1102 incident cases aged 25-64 years and 1147 age-matched population controls. The SULT1A1 genotype was not associated with overall breast cancer risk in this population. A possible association was suggested for postmenopausal breast cancer (adjusted odds ratio [OR] = 1.4, 95% CI = 0.9-2.1 for subject carrying the variant His allele). The SULT1A1 genotype was found to significantly modify postmenopausal breast cancer risk associated with a high BMI (>or=25 kg/m2) (p for interaction = 0.02), with an adjusted OR of 3.6 (95% CI = 1.5-8.7) for women with the Arg/His genotype compared with 1.1 (0.8-1.5) for women with the Arg/Arg genotype (no His/His genotype was identified in this study population). Similarly, the risk associated with a long duration (>or=30 years) of menstruation also substantially differed by the SULT1A1 genotype (p for interaction = 0.05), with an OR of 4.0 (95% CI = 1.3-12.8) for women with the Arg/His genotype and 1.4 (0.8-2.5) for women with the Arg/Arg genotype. Positive associations with blood levels of steroid hormones were also found generally to be more pronounced among women carrying the His allele. No similar effect modification was found for premenopausal breast cancer, however. These data suggest that the SULT1A1 Arg213His polymorphism may modify the effect of endogenous sex hormone exposures on postmenopausal breast cancer risk.

Endostatin polymorphism 4349G/A(D104N) is not associated with aggressiveness of disease in prostate [corrected] cancer.

Endostatin is an important inhibitory molecule which mediates the sequential steps involved in angiogenesis. Lower level or impaired function of endostatin is associated with a higher risk of developing malignant solid tumors and with a worse prognosis of the disease. The endostatin N104 polymorphism might be associated with an impaired ability to inhibit angiogenesis. We analyzed the tissues from 98 Caucasian prostate cancer patients for the presence of D104N polymorphism. The frequencies of homozygous 4349G/G(104D/D), and heterozygous 4349G/A(104D/N) were 83.67%(82/98) and 16.33%(16/98), respectively; no individuals were homozygous 4349A/A(104N/N). With the Fisher's exact test we found the genotype of D104N was not significantly related to age, tumor grade, PSA and clinical stage (P > 0.05). There was no difference in relapse free survival(RFS) or overall survival(OS) between patients with 104D/N and those with 104D/D (P = 0.8283, 0.3713 respectively). We concluded that endostatin polymorphism was not associated with the aggressiveness of prostate cancer in Caucasian patients.

Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma.

BACKGROUND: It has been suggested that genetic polymorphisms in certain glutathione-S-transferase (GST) genes reduce the effectiveness of detoxifying cytotoxins generated by chemotherapeutic agents, potentially resulting in enhanced clinical responses to chemotherapy. METHODS: The authors evaluated common polymorphisms in the GSTM1, GSTT1, and GSTP1 genes for associations with overall survival in 1034 patients with invasive breast carcinoma who were recruited into the Shanghai Breast Cancer Study between 1996 and 1998, treated with chemotherapy, and followed for a median of 5.3 years. RESULTS: After adjusting for age, tumor stage, and the use of radiotherapy and tamoxifen, women who were homozygous for the variant GSTP1 105Val allele had a 60% reduction in mortality risk compared with women who were homozygous for the Ile allele (hazard ratio, 0.4; 95% confidence interval, 0.2-0.8). No association was found with respect to any of the GSTM1 or GSTT1 genotypes. CONCLUSIONS: The results of the current study indicate a potential role for GSTP1 polymorphism in predicting the clinical outcomes of patients with breast carcinoma who are treated with chemotherapy.

Synergistic effects of STK15 gene polymorphisms and endogenous estrogen exposure in the risk of breast cancer.

STK15 is a member of a family of serine/threonine kinases that act as key regulators of chromosome segregation and cytokinesis. Over expression of the STK15 gene leads to centrosome amplification, chromosomal instability, aneuploidy, and transformation. It has been reported that the 91T --> A (Phe --> Ile at codon 31) polymorphism in the STK15 gene affects the function of this gene. We hypothesized that this polymorphism may interact with endogenous estrogen exposure in the risk of breast cancer and evaluated this hypothesis in a population-based, case-control study conducted among Chinese women in Shanghai. Genotyping assays were completed for 1,102 incident cases and 1,186 community controls. Participation and blood donation rates were over 90% and 80%, respectively. Elevated risks of breast cancer were found to be associated with the Phe/Ile [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7] and Ile/Ile (OR, 1.2; 95% CI, 0.9-1.6) genotypes at codon 31 of the STK15 gene, although the ORs were not statistically significant. The risk associated with this polymorphism was modified by factors related to endogenous estrogen exposure, such as high body mass index (BMI), high waist-to-hip ratio, long duration of lifetime menstruation, or long duration of menstruation before first live birth. In particular, a statistically significant interaction was found between BMI and the STK15 Phe(31)Ile polymorphism (P = 0.02) and a positive association with breast cancer risk for the Ile allele was found only among overweight (BMI >/= 25 kg/m(2)) women with adjusted ORs (95% CIs) of 3.3 (1.4-7.7) and 4.1 (1.7-9.8) associated with the Phe/Ile and Ile/Ile genotypes (Pfor trend <0.01), respectively. The findings from this study are consistent with the evidence from invitro and in vivo experiments, implicating an etiologic role of the STK15 gene in human breast cancer, and provide evidence for the modifying effects of genetic background on human cancer risk.