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Background: Pancreatic cancer is the fourth most common cause of mortality due to cancer, globally. It has a poor prognosis and is usually diagnosed at later stages when tumor resection is not possible. Heritability for pancreatic cancer is relatively high and clinically significant. Methods: A group of 24 pancreatic cancer patients with young age at onset, from a referral hospital in Tehran University of Medical Sciences were screened for mutations in 710 cancer relevant genes using next generation sequencing technology. Results: Two patients had pathogenic mutations in known pancreatic cancer susceptibility genes, BRCA1/2. Two other patients also had potentially pathogenic mutations in 2 novel candidate genes including PARP4 and EXO1. Conclusion: BRCA1/2 genes are the most commonly mutated pancreatic cancer susceptibility genes that should be considered in all pancreatic cancer cases with young age at onset or a family history of cancer. PARP4 and EXO1 also are potential candidate genes for susceptibility to pancreatic cancer. Identifying the hereditary cases of pancreatic cancer will help to offer more targeted treatments to the patients and also to prevent cancer in family members who might be a mutation carrier. © 2018 The Author(s).

To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios. Logistic regression models were used to assess risk associated with individual SNPs and overall PRS, and stratified by menopausal and receptor status. A total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and UST) showed statistically significant (p-value ≤ 0.05) evidence of association, either overall or when stratified by menopausal status or hormone receptor status. BC SNPs previously identified in Caucasian population showed evidence of replication in the Indian population mainly with respect to risk of postmenopausal and hormone receptor positive BC.

A region with a high risk for esophageal squamous cell carcinoma (ESCC) in northeast of Iran was identified more than three decades ago. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. Polymorphisms of several genes have been associated with susceptibility to esophageal cancer in various populations, but these have not been studied in Iran. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes which previously have been suggested to be associated with an increased risk of ESCC. We genotyped a primary set of samples from 451 Turkmen (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these SNPs were then studied in a validation set of 1668 cases and controls (Turkmen and non-Turkmen) under dominant and recessive models. In the joint sample set, five variants, from five different genes, showed significant associations with ESCC at the P = 0.05 level. For one variant, in ADH1B, the association was strong and was present in both Turkmen and non-Turkmen. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC under a recessive model (OR = 0.41, 95%, CI = 0.19 to 0.49; P = 4×10−4). For four additional variants, an association was present in the Turkmen subgroup, but the statistical significance of these was less compelling than for ADH1B. Two variants showed deleterious effects and two were protective. The G allele of the c.870A>G variant of CCND1 gene was associated with a 1.5-fold increased risk of ESCC under the recessive model (OR = 1.50, 95% CI = 1.14 to 2.16, P = 0.02) and the A allele of the rs1625895 variant of TP53 gene was associated with a 1.5-fold increased risk of ESCC under a dominant model (OR = 1.54, 95% CI = 1.21 to 4.07, P = 0.005). The C allele of the rs886205 variant of ALDH2 was associated with a decreased risk of ESCC under a recessive model (OR = 0.58, 95% CI = 0.34 to 0.87, P = 0.02) and the A allele of the rs7087131 variant of MGMT was associated with a decreased risk of ESCC under the recessive model (OR = 0.26, 95% CI = 0.05 to 0.49, P=0.01). These results confirm that genetic predisposition to ESCC plays a role in high incidence of this cancer among Turkmens who live in northeast of Iran.