Estimation of heritability for nine common cancers using data from genome‐wide association studies in Chinese population

Yurgelun

CA A Cancer J Clinicians

2018

130

106

The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape-altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm-shifting approaches to treatment of Lynch-syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018;68:217-231. © 2018 American Cancer Society.

Section: Germline Basis Of Familial Crcmentioning

confidence: 99%

Section: Germline Basis Of Familial Crcmentioning

confidence: 99%

Recent progress in Lynch syndrome and other familial colorectal cancer syndromes

Yurgelun

CA A Cancer J Clinicians

2018

130

106

“…In the past decade, genome‐wide association studies (GWAS) successfully identified lots of lung cancer susceptibility loci, such as CHRNA5 ‐ CHRNA3 ‐ CHRNB4 region of chromosome 15q25 and human leukocyte antigen region. Even so, at least 25% of lung cancer cases were never smokers and the heritability of lung cancer was also relatively low, nearly 18% . The risk factors of lung cancer still need more exploration.…”

Section: Introductionmentioning

confidence: 99%

Mendelian randomization study of telomere length and lung cancer risk in East Asian population

et al. 2019

Self Cite

Associations between telomere length and cancer risk have been investigated in many epidemiological studies, but the results are controversial. These associations may be biased by reverse causation or confounded by environmental exposures. To avoid potential biases, we used Mendelian randomization method to evaluate whether TL is the causal risk factor for lung cancer. We conducted Mendelian randomization analysis in two published East Asian GWAS studies (7127 cases and 6818 controls). We used both weighted genetic risk score and inverse‐variance weighting method to estimate the relationship between TL and lung cancer risk. Nonlinear test also used to detect potential association trends. We observed that increased weight GRS was associated with increased risk of lung cancer (OR = 2.25, 95%CI: 1.81‐2.78, P = 1.18 × 10−13). In different subtypes, weight GRS was significantly associated with lung adenocarcinoma risk (OR = 2.69, 95% CI: 2.11‐3.42, P = 7.20 × 10−16); while lung squamous cell carcinoma showed a marginal association (OR = 1.45, 95% CI = 1.01‐2.10, P = .047). Nonlinear analysis suggested a log‐linear dose‐response relationship between increased weight GRS and lung cancer risk. Our results indicated that longer TL increases lung cancer risk. Those biological mechanisms changes caused by long TL may play an important role in lung carcinogenesis.

“…Although tobacco smoking is a major lung cancer risk factor, genetic factors also play an important role in lung carcinogenesis. According to previous studies, common SNPs can explain approximately 12–21% heritability in lung cancer in Asian and European populations . Genome‐wide association studies (GWAS) have previously identified 45 susceptibility loci associated with lung cancer, and single nucleotide polymorphisms (SNPs) in the CHRNA3 , CHRNA5 , TERT and human leukocyte antigen (HLA) regions showed consistent and robust associations in different studies.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Dai

Huang

Amos³

et al. 2019

Intl Journal of Cancer

Self Cite

Genome‐wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large‐scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large‐scale meta‐analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome‐wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.