Tongzhang Zheng

A case-control study of oral cancer in Beijing, People's Republic of China. Associations with nutrient intakes, foods and food groups

A case-control study of oral cancer was conducted in Beijing, Peoples Republic of China to examine the association between dietary nutrient intake and risk of oral cancer, both in terms of estimated intake of nutrients and micro-nutrients, and in terms of specific foods and food groups. The study was hospital-based and controls were hospital in-patients matched for age and sex with the cases. The response rate for cases and controls was 100% and 404 case/control pairs were interviewed. The results suggest that increased protein and fat intake are related to a decreased risk of oral cancer. Carbohydrate intake, however, showed a moderate increased risk for oral cancer. Total carotene intake and carotene intake from fruits and vegetables are inversely associated with risk of oral cancer. A similar pattern was observed for dietary vitamin C intake. Dietary fibre derived from fruits and vegetables showed a strong negative association with oral cancer risk, but fibre derived from other sources did not exhibit any protective effect. At the level of foods and food groups, increased consumption of fresh meat, chicken and liver was significantly associated with a reduction in oral cancer risk: the tests for trend were all statistically significant at the P < 0.01 level. Consumption of common carp, hairtail, shrimp and lobster were also associated with decreased risk. Risk was found to increase with increasing consumption of millet and corn bread (P < 0.01) but to decrease with increasing consumption of rice (P < 0.01). Increased consumption of grapes, bananas, oranges, tangerines, peaches and pears were associated with reduced risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactation and breast cancer risk: a case-control study in Connecticut.

In this report, we examined the relationship between lactation and breast cancer risk, in a case–control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30–80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR=0.83, 95% CI, 0.63–1.09). An OR of 0.53 (95% CI, 0.27–1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23–0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.

A second follow-up of mortality in a cohort of pesticide applicators.

A cohort of 16,124 male pesticide applicators was matched with Social Security Administration and National Death Index (NDI) files through December 31, 1984. In all, 1,082 deaths were ascertained, and death certificates were obtained for 994 (92%). The standardized mortality ratio (SMR) for all causes of death was 98. Although a number of specific causes of death showed SMRs significantly below 100, only one category of cause of death showed a significantly elevated SMR--cancer of the lung, with an SMR of 135. Termite control operators (TCO)--the group with the greatest likelihood of exposure to chlordane and heptachlor--had an SMR for lung cancer of 97, compared with 158 for other pesticide operators. The excess of lung cancer in the non-TCO workers was limited to operators employed as such for less than five years.

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk.

Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case–control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR=1.9, 95% CI 1.2–3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR=2.5, 95% CI 1.1–5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of >250u2009kg of spirit-equivalents, had an almost seven-fold increased risk (OR=6.8, 95% CI 1.4–33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2–57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of >250u2009kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.

Changing patterns of bladder cancer in the USA: evidence of heterogeneous disease.

Study Type – Disease prevalence (retrospective cohort)

Identification of non-Hodgkin's lymphoma prognosis signatures using the CTGDR method

MOTIVATIONnAlthough NHL (non-Hodgkins lymphoma) is the fifth leading cause of cancer incidence and mortality in the USA, it remains poorly understood and is largely incurable. Biomedical studies have shown that genomic variations, measured with SNPs (single nucleotide polymorphisms) in genes, may have independent predictive power for disease-free survival in NHL patients beyond clinical measurements.nnnRESULTSnWe apply the CTGDR (clustering threshold gradient directed regularization) method to genetic association studies using SNPs, analyze data from an association study of NHL and identify prognosis signatures to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common subtypes of NHL. With the CTGDR method, we are able to account for the joint effects of multiple genes/SNPs, whereas most existing studies are single-marker based. In addition, we are able to account for the gene and SNP-within-gene hierarchical structure and identify not only predictive genes but also predictive SNPs within identified genes. In contrast, existing studies are limited to either gene or SNP identification, but not both. We propose using resampling methods to evaluate the predictive power and reproducibility of identified genes and SNPs. Simulation study and data analysis suggest satisfactory performance of the CTGDR method.

Fertility among testicular cancer survivors: a case-control study in the U.S.

IntroductionTesticular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49xa0years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility.MethodsTo examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted. The men were initially enrolled in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008–2009.ResultsTGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99–13.76) and difficulty in fathering children (OR 6.41; 2.72–15.13). Cases were also more likely to be tested for infertility (OR 3.65; 95% CI 1.55–8.59). Cases, however, did not differ from controls in actually fathering children (OR 1.37; 95% CI 0.88–2.15). These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery-plus-chemotherapy.DiscussionWhile expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men. It is possible that treatment for TGCT does not permanently affect fertility or, alternatively, that TGCT survivors attempt to father children with greater persistence or at younger ages than do other men.

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; ORu2009=u200921.14, 95% CI: 14.40–31.03, Pu2009=u20091.36u2009×u200910−54) and 14q32.13 (rs117410836, near TCL1; ORu2009=u20094.90, 95% CI: 3.45–6.96, Pu2009=u20098.75u2009×u200910−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of heterozygote advantage regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.