Amit Joshi

Harvard School of Public Health, Epidemiology, Research Fellow

University of Southern California, Preventive Medicine, Alumnus

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Jeffrey Townsend

Yale University

Phillip Melton

Curtin University, Perth

Nagehan Ersoy Tunalı

Istanbul Medeniyet University

Mohd Aminudin Mustapha

Universiti Malaysia Sarawak (UNIMAS)

Dr. Waheed Babatunde Yahya

University of Ilorin

Vicente E. Vega-Murillo

Universidad Veracruzana

Samer Ismail

Modern Science and Arts (MSA) university

Celia May

University of Leicester

Andrés Aravena

Istanbul University

Fezal Ozdemir

Ege University

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Papers by Amit Joshi

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

JAMA oncology, Jan 26, 2016

An improved model for risk stratification can be useful for guiding public health strategies of b... more An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention. To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for ...

Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer

The Faseb Journal, Apr 1, 2015

Physical activity from menarche to first pregnancy and risk of breast cancer

International journal of cancer, Jan 30, 2016

Breast tissue is particularly susceptible to exposures between menarche and first pregnancy, and ... more Breast tissue is particularly susceptible to exposures between menarche and first pregnancy, and a longer interval between these reproductive events is associated with elevated breast cancer risk. Physical activity during this time period may offset breast cancer risk, particularly for those at highest risk with longer menarche-to-first-pregnancy intervals. We used data from 65576 parous women in the Nurses' Health Study II free of cancer in 1989 (baseline) and recalled their leisure-time physical activity at ages 12 to 34 in 1997. Current activity was collected at baseline and over followup. Relative risks (RRs) were estimated using multivariable Cox proportional hazards regression models. Between 1989 and 2011, 2069 invasive breast cancer cases were identified. Total recreational activity between menarche and first pregnancy was not significantly associated with the risk of breast cancer. However, physical activity between menarche and first pregnancy was associated with signi...

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study

Cancer causes & control : CCC, Jan 22, 2016

There is suggestive but limited evidence for a relationship between meat intake and breast cancer... more There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95 % CI 1.18-1.71; trend p...

Response to Day et al

American journal of human genetics, Jan 4, 2016

Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium

Breast Cancer Research and Treatment, 2016

Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal bre... more Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.

A Cross-Cancer Genetic Association Analysis of the DNA repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast and Colorectal Cancer

Cancer Epidemiology Biomarkers & Prevention, 2015

Though DNA damage is an established mediator of carcinogenesis, GWAS have identified few signific... more Though DNA damage is an established mediator of carcinogenesis, GWAS have identified few significant loci, associated with cancer predisposition, within DNA repair gene regions. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. We conducted a cross-cancer analysis of 60,297 SNPs, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software package. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. We identified three susceptibility DNA repair genes, RAD51B (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 5.09 x 10-6), MSH5 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 5.09 x 10-6) and BRCA2 (p = 5.70 x 10-6). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Only three individual susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. These data suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria.

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Nature communications, 2015

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common gen... more Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of…

Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

Cancer medicine, Jan 7, 2015

Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. ... more Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with...

Adjusting for heritable covariates can bias effect estimates in genome-wide association studies

American journal of human genetics, Jan 5, 2015

In recent years, a number of large-scale genome-wide association studies have been published for ... more In recent years, a number of large-scale genome-wide association studies have been published for human traits adjusted for other correlated traits with a genetic basis. In most studies, the motivation for such an adjustment is to discover genetic variants associated with the primary outcome independently of the correlated trait. In this report, we contend that this objective is fulfilled when the tested variants have no effect on the covariate or when the correlation between the covariate and the outcome is fully explained by a direct effect of the covariate on the outcome. For all other scenarios, an unintended bias is introduced with respect to the primary outcome as a result of the adjustment, and this bias might lead to false positives. Here, we illustrate this point by providing examples from published genome-wide association studies, including large meta-analysis of waist-to-hip ratio and waist circumference adjusted for body mass index (BMI), where genetic effects might be bi...

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Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

Cancer Medicine, 2014

The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This stu... more The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case-Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1-2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0-1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk.

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Association of the Colorectal CpG Island Methylator Phenotype with Molecular Features, Risk Factors, and Family History

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 13, 2015

The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterize... more The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known. We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of colorectal cancer cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR). We found associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P < 0.0001), female sex [ccOR = 1.8; 95% confidence interval (CI), 1.5-2.1], older age (ccOR = 4.0 comparing over 70 years vs. under 50; 95% CI, 3.0-5.5), and family history of CRC (ccOR = 0.6; 9...

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Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium

American journal of epidemiology, Jan 15, 2014

Additive interactions can have public health and etiological implications but are infrequently re... more Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We a...

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Association of breast cancer risk loci with breast cancer survival

International Journal of Cancer, 2015

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TN... more The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; Ptrend =2.84 × 10(-4) ; HRheterozygotes =0.71; 95% CI: 0.55-0.92; HRhomozygotes =0.48; 95% CI: 0.31-0.76; P2DF =1.45 × 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; Ptrend =6.6 × 10(-4) ; HRheterozygotes =0.96 95% CI: 0.90-1.03; HRhomozygotes = 1.21; 95% CI: 1.09-1.35; P2DF =1.25 × 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. This article is protected by copyright. All rights reserved.

Vitamin D-associated genetic variation and risk of breast cancer in the Breast and Prostate Cancer Cohort Consortium (BPC3)

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 26, 2014

Background:Two recent genome-wide association studies (GWAS) identified SNPs related to circulati... more Background:Two recent genome-wide association studies (GWAS) identified SNPs related to circulating 25-hydroxyvitamin D [25(OH)D] concentration in or near four genes. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts. Methods:SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer. Results:We found no association between any of the four SNPs or their polygenic score and breast cancer risk. Conclusions:Our findings do not support an association between vitamin D status, as reflected by 25(OH)D-related genotypes, and breast cancer risk. Impact: The...

PD31-06 Dairy Intake and Prostate Cancer Risk: Results from the California Collaborative Prostate Cancer Study

The Journal of Urology, 2014

Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk

Environmental Health Perspectives, 2011

Background: Previous research indicates increased prostate cancer risk for pesticide applicators ... more Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. oBjectives: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated inter actions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. , respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC geno type. Carbofuran and S-ethyl dipropyl thio carbamate (EPTC) inter acted similarly with rs1983132; however, these inter actions did not meet an FDR < 0.2. conclusions: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk. key words: DNA repair, gene-environment inter actions, pesticide, polymorphisms, prostate cancer.

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Abstract 2775: Meat intake, genetic variation in carcinogen metabolic enzymes, and prostate cancer risk in a multiethnic case-control study of non-Hispanic Whites, African Americans and Hispanics

Cancer Research, 2011

Abstract 2621: Relative excess risk due to interactions between GWAS-identified susceptibility loci and other breast cancer risk factors

Cancer Research, 2012

Abstract A97: Dietary nitrosamines, genetic variation in DNA repair and metabolism genes, and bladder cancer risk in the Los Angeles Bladder Cancer Study

Cancer Prevention Research, 2012

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

JAMA oncology, Jan 26, 2016

Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer

The Faseb Journal, Apr 1, 2015

Physical activity from menarche to first pregnancy and risk of breast cancer

International journal of cancer, Jan 30, 2016

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study

Cancer causes & control : CCC, Jan 22, 2016

Response to Day et al

American journal of human genetics, Jan 4, 2016

Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium

Breast Cancer Research and Treatment, 2016

A Cross-Cancer Genetic Association Analysis of the DNA repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast and Colorectal Cancer

Cancer Epidemiology Biomarkers & Prevention, 2015

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Nature communications, 2015

Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

Cancer medicine, Jan 7, 2015

Adjusting for heritable covariates can bias effect estimates in genome-wide association studies

American journal of human genetics, Jan 5, 2015

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Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

Cancer Medicine, 2014

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Association of the Colorectal CpG Island Methylator Phenotype with Molecular Features, Risk Factors, and Family History

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 13, 2015

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American journal of epidemiology, Jan 15, 2014

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Association of breast cancer risk loci with breast cancer survival

International Journal of Cancer, 2015

Vitamin D-associated genetic variation and risk of breast cancer in the Breast and Prostate Cancer Cohort Consortium (BPC3)

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 26, 2014

PD31-06 Dairy Intake and Prostate Cancer Risk: Results from the California Collaborative Prostate Cancer Study

The Journal of Urology, 2014

Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk

Environmental Health Perspectives, 2011

Download

Abstract 2775: Meat intake, genetic variation in carcinogen metabolic enzymes, and prostate cancer risk in a multiethnic case-control study of non-Hispanic Whites, African Americans and Hispanics

Cancer Research, 2011

Abstract 2621: Relative excess risk due to interactions between GWAS-identified susceptibility loci and other breast cancer risk factors

Cancer Research, 2012

Abstract A97: Dietary nitrosamines, genetic variation in DNA repair and metabolism genes, and bladder cancer risk in the Los Angeles Bladder Cancer Study

Cancer Prevention Research, 2012

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